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Ehlers-danlos syndrome, progeroid type, 2

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: b3galt6

Description

A number sign (#) is used with this entry because Ehlers-Danlos syndrome progeroid type 2 (EDSP2) is caused by compound heterozygous mutation in the B3GALT6 gene (615291) on chromosome 1p36.

Mutation in the B3GALT6 gene can also cause spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMDJL1; 271640), which has overlapping features with EDSP.The features of the progeroid form of Ehlers-Danlos syndrome include an aged appearance, developmental delay, short stature, craniofacial disproportion, generalized osteopenia, defective wound healing, hypermobile joints, hypotonic muscles, and loose but elastic skin (Okajima et al., 1999).

For a discussion of genetic heterogeneity of EDSP, see EDSP1 (130070).

Molecular genetics

In 4 patients from 3 families with a progeroid form of EDS who did not have mutations in the B4GALT7 gene, Nakajima et al. (2013) performed Sanger sequencing of the B3GALT6 gene and found that all 4 patients were compound heterozygous for a frameshift and a missense mutation (615291.0007-615291.0011). Nakajima et al. (2013) showed that the GalT-II activities of a missense mutation that was common to 2 of the families (S309T; 615291.0008) were significantly decreased compared to wildtype, suggesting loss of function. The mutations were not detected in more than 200 ethnically matched controls or in public databases, including the 1000 Genomes Database.

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Weight]; Low weight

HEAD AND NECK: [Face]; Prominent forehead; Flat face; [Eyes]; Prominent eyes; Proptosis; Blue sclerae; [Mouth]; Long upper lip; Cleft palate (rare)

CHEST: [Ribs, sternum, clavicles, and scapulae]; Pectus excavatum (rare)

SKELETAL: Large joint laxity; [Spine]; Platyspondyly; Kyphoscoliosis; Anterior beak of vertebral body; [Pelvis]; Short ilia; Hip dislocation; Prominent lesser trochanter; [Limbs]; Restricted elbow movement; Elbow malalignment; Metaphyseal flaring; Epiphyseal dysplasia of femoral head; [Hands]; Spatulate finger; Finger laxity; Hand contracture (rare); Advanced carpal ossification; Carpal fusion (rare); Metacarpal shortening; [Feet]; Clubfeet

SKIN, NAILS, HAIR: [Skin]; Doughy skin; Hyperextensible skin; Cutis laxa; [Hair]; Sparse hair

NEUROLOGIC: [Central nervous system]; Hypotonia; Developmental delay (rare)

MOLECULAR BASIS: Caused by mutation in the UDP-Gal:beta-Gal beta-1,3-galactosyltransferase polypeptide 6 gene (B3GALT6, 615291.0007)

Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: b3galt6, kif22

Description

A number sign (#) is used with this entry because spondyloepimetaphyseal dysplasia with joint laxity type 1 with or without fractures (SEMDJL1) is caused by homozygous or compound heterozygous mutation in the B3GALT6 gene (615291) on chromosome 1p36.

Mutation in the B3GALT6 gene can also cause a progeroid type of Ehlers-Danlos syndrome (EDSP2; 615349), which has overlapping features with SEMDJL1.Spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMDJL1) is characterized by vertebral abnormalities and ligamentous laxity that result in spinal misalignment and progressive severe kyphoscoliosis, thoracic asymmetry, and respiratory compromise resulting in early death. Nonaxial skeletal involvement includes elbow deformities with radial head dislocation, dislocated hips, clubfeet, and tapered fingers with spatulate distal phalanges. Many affected children have an oval face, flat midface, prominent eyes with blue sclerae, and a long philtrum. Palatal abnorma...

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Dwarfism; [Weight]; Low weight

HEAD AND NECK: [Face]; Oval face; Flat midface; Prominent forehead; Micrognathia; [Eyes]; Prominent eyes; Blue sclera; Myopia; Congenital myopia; Lens dislocation; Proptosis; [Mouth]; Cleft palate (31% of patients); High-arched palate (12% of patients); Long philtrum; Long upper lip; [Neck]; Short neck

CARDIOVASCULAR: [Heart]; Atrial septal defect; Ventricular septal defect; Mitral insufficiency; Bicuspid aortic valve

CHEST: [External features]; Thoracic asymmetry; [Ribs, sternum, clavicles, and scapulae]; Anterior flaring of ribs; Cupped ribs; 11 pairs of ribs

SKELETAL: Joint laxity; Joint dislocation; Spondyloepimetaphyseal dysplasia; Joint contractures; Osteoporosis; Spontaneous fractures; [Spine]; Progressive kyphoscoliosis; Ovoid vertebrae (infancy); Platyspondyly (childhood); Irregular endplates (childhood); Gross spinal malalignment; Anterior beak of vertebral body; Scoliosis; [Pelvis]; Large, flared iliac wings; Hypoplastic iliac body; Narrow pubic bones; Delayed ossification of femoral capital epiphyses; Hip dislocation; Hip subluxation; Short femoral necks; Coxa valga; Prominent lesser trochanter; [Limbs]; Genu valga (80% of patients); Radial head dislocation; Radial head subluxation; Radial bowing; Restricted elbow movement; Elbow malalignment; Short, slender long bones; Wide metaphyses; Metaphyseal flaring; Epiphyseal dysplasia of femoral head; Abnormal trabecular pattern; [Hands]; Hypermobile digits; Spatulate terminal phalanges (especially thumbs); Short metacarpals; Hand contracture (rare); Advanced carpal ossification; Carpal fusion (rare); [Feet]; Talipes equinovarus; Pes planus; H...
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Spondyloperipheral dysplasia

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: col2a1
Spondyloperipheral dysplasia

Clinical features

A number sign (#) is used with this entry because spondyloperipheral dysplasia is caused by heterozygous mutation in the alpha-1 type II collagen gene (COL2A1; 120140) on chromosome 12q13.Kelly et al. (1977) described a father and 2 children (son and daughter) with an identical skeletal dysplasia of unusual type. It fell generally in the category of spondyloepiphyseal dysplasias. Platyspondyly and severe hip changes were present. The hands and feet were very short as in peripheral dysostosis. The ulna was very short distally, so that it showed deficiency at the wrist. Some of the metatarsals were particularly short. The father was 144 cm tall; the 31-year-old daughter was 142 cm tall; and the 30-year-old son was 154 cm tall. The pedigree was equally consistent with autosomal dominant or autosomal recessive inheritance because the affected father was married to his first cousin and came himself from a consanguineous mating. The families reported by Sybert et al. (1979) and by Vanek (1983) have some similarities; in these families, inheritance seems to have been autosomal dominant. The single case reported by Goldblatt and Behari (1987) also has some similarities. The patient was 108 cm tall at the age of 20, with an arm span of 125.5 cm; the forearms showed mild bilateral bowing. The shortening of the bones of the hands and feet was possibly more striking in the patients reported by Kelly et al. (1977).

Sorge et al. (1995) described the disorder in a mother and 3 of her children, 2 daughters and a son. In addition to platyspondyly with endplate indentations and brachydactyly, the proband had a characteristic, 'pugilistic' face, sensorineural deafness, and mental retardation.

Zankl et al. (2004) reported 2 patients with findings similar to those described by Zabel et al. (1996): clubfeet, midface hypoplasia, early-onset high grade myopia, platyspondyly, epiphyseal dysplasia,...

Symptoms

INHERITANCE: Autosomal dominant

GROWTH: [Height]; Short stature

HEAD AND NECK: [Face]; 'Pugilistic facies'; Midface hypoplasia; [Ears]; Hearing loss, sensorineural

CHEST: [External features]; Pectus carinatum; Barrel-shaped chest

SKELETAL: Spondyloepiphyseal dysplasia; [Spine]; Platyspondyly, mild; Biconcave disc (fish-mouth vertebrae); Kyphosis; [Pelvis]; Short ilia; Horizontal acetabulae; Flattened capital femoral epiphyses; Acetabular spurs (infancy); [Limbs]; Short ulna; Absent styloid processes; Limited elbow extension; [Hands]; Short fingers; Broad hands; Very short distal phalanges (2nd, 3rd, 4th, 5th); Short metacarpals (2nd, 3rd, 4th, 5th); Cone-shaped epiphyses; Short, broad thumbs; Brachydactyly E-like changes; Short proximal and middle phalanges; [Feet]; Short feet; Short phalanges; Short metatarsals (4th)

MOLECULAR BASIS: Caused by mutation in the collagen II, alpha-1 polypeptide gene (COL2A1, 120140.0030)
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Spondyloperipheral dysplasia

Retrieved: 27-07-2015
Source: GHR (Original article)
Associated genes: col2a1
Spondyloperipheral dysplasia

What is spondyloperipheral dysplasia?

Spondyloperipheral dysplasia is a disorder that impairs bone growth. This condition is characterized by flattened bones of the spine (platyspondyly) and unusually short fingers and toes (brachydactyly), with the exception of the first (big) toes. Other skeletal abnormalities associated with spondyloperipheral dysplasia include short stature, shortened long bones of the arms and legs, exaggerated curvature of the lower back (lordosis), and an inward- and upward-turning foot (clubfoot). Additionally, some affected individuals have nearsightedness (myopia), hearing loss, and intellectual disability.

How common is spondyloperipheral dysplasia?

This condition is rare; only a few affected individuals have been reported worldwide.

What genes are related to spondyloperipheral dysplasia?

Spondyloperipheral dysplasia is one of a spectrum of skeletal disorders caused by mutations in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen. This type of collagen is found mostly in the clear gel that fills the eyeball (the vitreous) and in cartilage. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Type II collagen is essential for the normal development of bones and other connective tissues that form the body's supportive framework. Mutations in the COL2A1 gene interfere with the assembly of type II collagen molecules, reducing the amount of this type of collagen in the body. Instead of forming collagen molecules, the abnormal COL2A1 protein builds up in cartilage cells (chondrocytes). These changes disrupt the normal development of bones and other connective tissues, leading to the signs and symptoms of spondyloperipheral dysplasia. Read more about the COL2A1 gene.

How do people inherit spondyloperipheral dysplasia?

This condition is probably inherited in an autosomal dominant pattern, which means on...

Keywords

spondyloperipheral dysplasia,Collagen Diseases,Osteochondrodysplasias,Skin and Connective Tissue Diseases,Connective Tissue Diseases,Bone Diseases,Musculoskeletal Diseases,Bone Diseases, Developmental,Bones, muscles, and connective tissues,Ear, nose, and throat,Eyes and vision,type II collagenopathy,COL2A1,COL2A1 gene,SPD,spondyloperipheral dysplasia with short ulna,National Library of Medicine,NLM,National Institutes of Health,NIH,health problem,health problems,disease,diseases,human genetics,gene,genes,genetic disease,genetic conditions,genetic disorders,medical genetics,genetics education,genetics glossary,gene reference,genetics reference,human genetic health,genomic medicine,molecular medicine,genetic testing,genomic medicine,gene therapy,pharmacogenomics,genetic counseling,counseling,gene testing,genome,hereditary family history,future of medicine,Disease and Gene Association,congenital,heritable disorders,inherited disorders,heritable diseases,inherited diseases,family disorders,family diseases
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Spondyloperipheral dysplasia

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Associated genes: col2a1
Spondyloperipheral dysplasia Spondyloperipheral dysplasia is an autosomal dominant disorder of bone growth. The condition is characterized by flattened bones of the spine (platyspondyly) and unusually short fingers and toes (brachydactyly). Some affected individuals also have other skeletal abnormalities, short stature, nearsightedness (myopia), hearing loss, and mental retardation. Spondyloperipheral dysplasia is a subtype of collagenopathy, types II and XI.

Cause and Genetics

Spondyloperipheral dysplasia is one of a spectrum of skeletal disorders caused by mutations in the COL2A1 gene, located on chromosome 12q13.11-q13.2. The protein made by this gene forms type II collagen, a molecule found mostly in cartilage and in the clear gel that fills the vitreous humour (the eyeball). Type II collagen is essential for the normal development of bones and other connective tissues (the tissues that form the body's supportive framework). Mutations in the COL2A1 gene interfere with the assembly of type II collagen molecules. The protein made by the altered COL2A1 gene cannot be used to make type II collagen, resulting in a reduced amount of this type of collagen in the body. Instead of forming collagen molecules, the abnormal protein builds up in cartilage cells (chondrocytes). These changes disrupt the normal development of bones, leading to the signs and symptoms of spondyloperipheral dysplasia. The disorder is believed to be inherited in an autosomal dominant manner. This indicates that the defective gene responsible for the disorder is located on an autosome (chromosome 12 is an autosome), and only one copy of the defective gene is sufficient to cause the disorder, when inherited from a parent who has the disorder.

External links

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Ruvalcaba syndrome

Retrieved: 27-07-2015
Source: OMIM (Original article)

Clinical features

Ruvalcaba et al. (1971) described 2 brothers, born to unrelated parents, who showed mental retardation, short stature, microcephaly, peculiar facies with hooked nose and small mouth, narrow thoracic cage with pectus carinatum, hypoplastic genitalia, hypoplastic 'onion skin' cutaneous lesions, and skeletal deformities including short metatarsals and metacarpals and epiphysitis of the spine. Because 2 female maternal cousins showed some of the same features, X-linked semi-dominant inheritance was considered. One of the girls seems to have been fully affected, however. She died at age 17 years with congenital hydrocephalus and the Dandy-Walker anomaly.

Geormaneanu et al. (1978) reported a 7-year-old boy and his father with the syndrome and a possibly coincidental t(13q;14q) translocation.

Bianchi et al. (1984) described a single case in an Italian male.

Under the designation of Ruvalcaba syndrome, Sugio and Kajii (1984) described a kindred with 9 affected persons in 4 generations. They showed postnatal growth retardation, oval face with high forehead, antimongoloid slant of palpebral fissures (the kindred was Japanese), small, beaked nose with hypoplastic nasal alae, small downturned mouth with thin vermilion borders, pointed chin, and short digits. This kindred differed from that reported by Ruvalcaba et al. (1971) in the lack of mental retardation. Hunter (1985) disagreed with the diagnosis of Sugio and Kajii (1984) and considered the disorder to be different from Ruvalcaba syndrome. He pointed to the absence of mental retardation and microcephaly and the presence of sparse hair, beaked nose, long upper lip, and severe degree of metacarpal phalangeal shortness. Niikawa and Kamei (1986) proposed that this is a separate entity which should be called trichorhinophalangeal syndrome, type III (TRPS3; 190351).

Adachi et al. (2010) reported a Japanese girl with clinical manifestations identical to those reported by Ruvalcaba et al. (1971). Born of unrelated parents, she presented at age 6 months with failure to thrive, multiple congenital anomalies, and developmental delay. She had microce...

Symptoms

INHERITANCE: Autosomal dominant

GROWTH: [Height]; Short stature

HEAD AND NECK: [Head]; Microcephaly; [Eyes]; Downslanting palpebral fissures; Central tapetoretinal dystrophy; [Nose]; Narrow nose; Hypoplastic alae nasi; [Teeth]; Crowded teeth

CHEST: [External features]; Narrow chest; [Breasts]; Large areolae

GENITOURINARY: [External genitalia, male]; Inguinal hernia; [Internal genitalia, male]; Cryptorchidism

SKELETAL: [Spine]; Scoliosis; Kyphosis; [Limbs]; Short limbs; Limitation of elbow extension; Prominent elbows; [Hands]; Small hands; Short metacarpals; Short phalanges; [Feet]; Small feet; Short metatarsals

NEUROLOGIC: [Central nervous system]; Mental retardation

ENDOCRINE FEATURES: Delayed puberty
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Desbuquois syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: cant1, chst3

Desbuquois syndrome (DBQD) is an osteochondrodysplasia characterized by severe micromelic dwarfism, facial dysmorphism, joint laxity with multiple dislocations, vertebral and metaphyseal abnormalities and advanced carpotarsal ossification. Two forms have been distinguished on the basis of the presence (type 1) or the absence (type 2) of characteristic hand anomalies. A variant form of DBQD, Kim variant (see these terms), has also been described and is characterized by short stature and articular, minor facial and significant hand anomalies. To date, less than 50 cases have been described in the literature. DBQD is characterized by severe micromelic dwarfism, facial dysmorphism (round flat face, prominent eyes, midface hypoplasia, short nose, microstomia, long upper lip with flat philtrum, microretrognathia, often resulting in isolated Pierre Robin syndrome (see this term)), thoracic hypoplasia, kyphoscoliosis, severe joint laxity with dislocation, and osteopenia. Additional features include glaucoma, cardiac septal defects, lung hypoplasia, obesity and clubbed feet with rocker bottom appearance. Two forms have been distinguished on the basis of the presence (type 1) or the absence (type 2) of characteristic hand anomalies (accessory ossification center distal to the second metacarpal, bifid distal phalanx, or thumb with delta-shaped phalanx). A variant form of DBQD, Kim variant, has been described in 7 patients originating from Korea and Japan, and is characterized by short stature, articular and minor facial anomalies, together with significant hand anomalies including short metacarpals and elongated phalanges with advanced carpal bone age. DBQD type 1 and Kim variant are caused by mutation in the gene CANT1 (17q25.3). However, the function of CANT1 is still unknown. Mutations in the gene XYLT1 (16p12) has been reported to cause DBQD type 2. XYLT1 encodes xylosyltransferase 1 which is involved in proteoglycan synthesis. However not all DBQD type 2 have XYL...
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Desbuquois dysplasia 1

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: cant1, chst3

Description

A number sign (#) is used with this entry because of evidence that Desbuquois dysplasia-1 (DBQD1) is caused by homozygous or compound heterozygous mutation in the CANT1 gene (613165) on chromosome 17q25.3.Desbuquois dysplasia (DBQD) is an autosomal recessive chondrodysplasia belonging to the multiple dislocation group and characterized by severe prenatal and postnatal growth retardation (stature less than -5 SD), joint laxity, short extremities, and progressive scoliosis. The main radiologic features are short long bones with metaphyseal splay, a 'Swedish key' appearance of the proximal femur (exaggerated trochanter), and advanced carpal and tarsal bone age with a delta phalanx (summary by Huber et al., 2009).

Desbuquois dysplasia is clinically and radiographically heterogeneous, and had been classified into 2 types based on the presence (type 1) or absence (type 2) of characteristic hand anomalies, including an extra ossification center distal to the second m...

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Short stature, disproportionate; Dwarfism, short-limb, prenatal onset; Average adult height 114 cm; [Weight]; Obesity

HEAD AND NECK: [Face]; Round face; Midface hypoplasia; Microretrognathia; [Eyes]; Prominent eyes; Bulging eyes; Congenital glaucoma; Myopia, apparent with age; [Nose]; Short nose; Flat nasal bridge; [Mouth]; Microstomia; [Neck]; Short neck

CHEST: [External features]; Narrow thorax; [Ribs, sternum, clavicles, and scapulae]; Widened anterior ribs

SKELETAL: Joint laxity; Joint dislocations; Osteoporosis; Osteoarthritis, progressive; [Spine]; Coronal cleft; Sagittal cleft; Scoliosis; Marked lordosis; Kyphosis; Platyspondyly; Narrowness of intervertebral disc space; [Pelvis]; Flat acetabular roof; Coxa vara; Coxa valga; Elevated greater trochanter; 'Swedish key' proximal femur (flat proximal femoral metaphysis with medial spike and exaggerated lesser tuberosity); 'Monkey wrench' appearance of the femoral heads; Short wide femoral neck; [Limbs]; Flat epiphyses; Wide metaphyses; Radioulnar dislocation; Proximal fibular overgrowth; Genu varum; [Hands]; Brachydactyly; Phalangeal dislocations; Radial deviation of the fingers; Delta phalanx/delta-like phalanx; Bifid distal phalanx of thumb; Accessory ossification proximal phalanx, 2nd digit; Short first metacarpal; Short metacarpals; Advanced carpal bone age; Shortened distal phalanges; [Feet]; Phalangeal dislocations; Medial deviation of the foot; Delta phalanx/delta-like phalanx; Bifid distal phalanx of great toe; Enlarged first metatarsal; Short metatarsals; Advanced tarsal ossification; Elongated second and third toes; Sandal gap; Club foot; Pes planus

NEUROLOGIC: [Central nervous ...
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Trichorhinophalangeal syndrome, type iii

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: trps1

Clinical features

A number sign (#) is used with this entry because of evidence that type III TRPS is caused by mutation in the TRPS1 gene (604386), which is also the site of mutation in type I TRPS (190350).Sugio and Kajii (1984) described a kindred in which 9 persons in 4 generations showed a syndrome of sparse hair, beaked nose, long upper lip, and severe metacarpophalangeal shortening. They reported the condition as an example of Ruvalcaba syndrome (180870); however, as pointed out by Hunter (1985), the disorder could be differentiated from Ruvalcaba syndrome by the absence of mental retardation and microcephaly and the presence of other changes resembling those of trichorhinophalangeal syndrome I (190350). The abnormalities of the hands and feet present in the patients of Sugio and Kajii (1984) were more severe, however, than those of TRPS1 patients. Niikawa and Kamei (1986) reported on a sporadic case who had similar manifestations and proposed that the condition should be recognized as a new syndrome known as TRPS type III, or Sugio-Kajii syndrome. Nagai et al. (1994) added another family in which 4 persons in 3 generations were affected with 1 instance of male-to-male transmission. The sparse hair, 'pear-shaped nose' clearly demonstrated in the figures, and cone-shaped epiphyses were features like those of TRPS types I and II (TRPS2; 190350), but the presence of severe generalized shortening of all phalanges and metacarpals differentiated the condition from TRPS1 and the absence of mental deficiency and exostoses from TRPS2.

Vilain et al. (1999) reported a case of TRPS III in a patient of European descent. The patient had typical features ...

Symptoms

INHERITANCE: Autosomal dominant

GROWTH: [Height]; Short stature; Normal birth length; [Weight]; Normal birth weight

HEAD AND NECK: [Face]; Long, flat philtrum; [Ears]; Protruding ears; [Eyes]; Laterally sparse eyebrows; [Nose]; Pear-shaped nose; Hypoplastic alae nasi; [Mouth]; Thin upper lip; [Teeth]; Crowded teeth; Supernumerary teeth

SKELETAL: Mild osteopenia; Delayed bone age before puberty; Accelerated bone age after puberty; [Spine]; Scoliosis; [Pelvis]; Coxa plana; Coxa magna; [Limbs]; Absence of exostoses; [Hands]; Short hands; Cone-shaped epiphyses (middle phalanges); Severe brachydactyly; Short metacarpals; Short phalanges; [Feet]; Short feet; Short metatarsals

SKIN, NAILS, HAIR: [Hair]; Sparse hair; Laterally sparse eyebrow

NEUROLOGIC: [Central nervous system]; Normal intelligence

MISCELLANEOUS: Cone-shaped epiphyses usually not present before age 2 years; Allelic to TRP1 (190350); TRP2 (Langer-Giedion syndrome, 150230) is a microdeletion syndrome involving deletions of both the TRPS1 (604386) and EXT1 (608177) genes

MOLECULAR BASIS: Caused by mutations in the zinc finger transcription factor TRPS1 gene (TRPS1, 604386.0007)
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Metaphyseal chondrodysplasia with retinitis pigmentosa

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

Phillips et al. (1981) described a brother and sister, children of normal parents, who had retinitis pigmentosa (leading to near blindness) and metaphyseal chondrodysplasia (with particularly marked shortening of the metacarpals and terminal phalanges).

Symptoms

Eyes: Retinitis pigmentosa

Skel: Metaphyseal dysplasia; Short metacarpals; Short terminal phalanges

Inheritance: Autosomal recessive
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Spondylocheirodysplasia, ehlers-danlos syndrome-like

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: slc39a13

Clinical features

A number sign (#) is used with this entry because the spondylocheirodysplastic form of Ehlers-Danlos syndrome (SCD-EDS) is caused by homozygous mutation in the zinc transporter gene SLC39A13 (608735) on chromosome 11p11.2.Giunta et al. (2008) described a 'spondylocheiro dysplastic form of Ehlers-Danlos syndrome' in 6 patients from 2 consanguineous families. Clinical features included postnatal growth retardation, moderate short stature, protuberant eyes with bluish sclerae, hands with finely wrinkled palms, atrophy of the thenar muscles, and tapering fingers. Patients had thin, hyperelastic skin and hypermobile small joints consistent with an Ehlers-Danlos-like phenotype. Radiologic features included mild to moderate platyspondyly, mild to moderate osteopenia of the spine, small ileum, flat proximal femoral epiphyses, short, wide femoral necks, and broad metaphyses (elbows, knees, wrists, and interphalangeal joints).

Biochemical features

Giunta et al. (2008) found that all 6 patients with SCD-EDS had an increased lysyl pyridinoline/hydroxylysyl pyridinoline (LP/HP) ratio indicating underhydroxylation of collagen. The ratio in patients (mean 0.89 +/- 0.18) was lower than that in individuals with EDS VI (225400; mean 5.97 +/- 0.99) but markedly higher than that in contr...

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Short stature, moderate; [Weight]; Birthweight at or below 3rd centile; [Other]; Growth retardation, postnatal

HEAD AND NECK: [Eyes]; Protuberant eyes; Blue sclerae; Downslanting palpebral fissures; Corneal diameter, normal; [Mouth]; High palate; Bifid uvula; [Teeth]; Delayed eruption of teeth; Malocclusion; Hypodontia

SKELETAL: [Spine]; Platyspondyly; Osteopenia; Irregular endplates; [Pelvis]; Small ilia; Short, wide femoral neck; Mildly flattened proximal femoral epiphyses; [Limbs]; Joint laxity (elbow); Widened metaphyses (elbows and knees); [Hands]; Small joint laxity; Finger contractures; Slender, tapered fingers; Finely wrinkled palms; Thenar muscle atrophy; Hypothenar muscle atrophy; Inability to adduct thumbs; Short metacarpals; Short phalanges; Widened metaphyses (metacarpal and phalanges); Flattened epiphyses (metacarpal and phalanges); [Feet]; Pes planus

SKIN, NAILS, HAIR: [Skin]; Velvety, smooth skin; Hyperelastic skin; Thin skin; Easy bruisability; Finely wrinkled palms; Prominent veins; Cigarette-paper scars; Delayed wound healing

MUSCLE, SOFT TISSUE: Thenar muscle atrophy; Hypothenar muscle atrophy

LABORATORY ABNORMALITIES: Lysyl pyridinoline/hydroxylysyl pyridinoline (LP/HP) ratio approximately 1; Normal lysyl hydroxylase activity; Normal prolyl 4-hydroxylase activity

MISCELLANEOUS: Waddling gait

MOLECULAR BASIS: Caused by mutation in the solute carrier family 39 (zinc transporter), member 13 gene (SLC39A13, 608735.0001)
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Brachydactyly, type e, with atrial septal defect, type ii

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

In a kindred in which multiple members had somewhat short stature, round facies, and brachydactyly type E (113300), Czeizel and Goblyos (1989) described also the appearance of the secundum type of atrial septal defect (ASD II). The shortening of the metacarpals was most pronounced in the 4th metacarpal, but not limited to that bone.

Symptoms

Growth: Short stature

Facies: Round facies

Limbs: Brachydactyly; Short metacarpals, esp. 4th; Variable short metatarsals

Cardiac: Atrial septal defect (ASD II)

Inheritance: Autosomal dominant
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Beemer-Ertbruggen syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)

Beemer-Ertbruggen syndrome is a lethal malformation syndrome reported in 2 brothers of first-cousin parents that is characterized by hydrocephalus, cardiac malformation, dense bones, and unusual facies with down-slanting palpebral fissures, bulbous nose, broad nasal bridge, micrognathia and a long upper lip. Transmission is likely autosomal recessive. There have been no further descriptions in the literature since 1984. Last update: January 2014
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Brachydactyly, preaxial, with hallux varus and thumb abduction

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

Christian et al. (1972) described short thumbs and first toes with abduction of these digits. The shortening involves the metacarpals, metatarsals, and distal phalanges, while the proximal and middle phalanges are of normal length. Although no male-to-male transmission was observed, males and females were affected to a similar degree. Four successive generations and 6 sibships were affected. All 8 affected members were mentally retarded. Sharma et al. (1994) described a father and daughter with the same form of brachydactyly but without mental retardation. The changes in the hands and feet were much like those reported by Mononen et al. (1992) (see 301940), but Sharma et al. (1994) considered that to be a different entity because it showed missing phalanges, short stature, and epiphyseal and metaphyseal changes indicative of a skeletal dysplasia.

Symptoms

Limbs: Short abducted thumbs; Short abducted first toes; Short distal phalanges; Short metacarpals; Short metatarsals; Normal proximal and middle phalanges

Inheritance: Autosomal dominant
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Brachydactyly - preaxial hallux varus

Retrieved: 27-07-2015
Source: Orphanet (Original article)

Preaxial brachydactyly-hallux varus syndrome is characterized the association of hallux varus with short thumbs and first toes (involving the metacarpals, metatarsals, and distal phalanges; the proximal and middle phalanges are of normal length) and abduction of the affected digits. The syndrome has been described in eight affected individuals from four successive generations of one family. Intellectual deficit was observed in all reported individuals. Transmission appears to be autosomal dominant. Expert reviewer(s) Pr R.C. [Raoul] HENNEKAM Last update: July 2008
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Synostoses, tarsal, carpal, and digital

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

Pearlman et al. (1964) described mother and daughter with multiple carpal and tarsal synostoses (carpal and tarsal coalition) as well as radial-head subluxation, aplasia or hypoplasia of the middle phalanges, and metacarpophalangeal synostoses. The latter synostoses seem comparable to those that occur in the 2 more distal joints in the 2 forms of symphalangism (185700, 185800). Although the authors felt this to be the disorder described by Nievergelt (see Nievergelt syndrome, 163400), this is almost certainly not the case but a distinct entity is involved. Bersani and Samilson (1957) described a mother and her daughter and son with massive synostosis of tarsal bones. No specific statement was made about the state of the carpal bones. Wray and Herndon (1963) observed calcaneonavicular coalition in 3 generations. Isolated fusion of carpal and tarsal bones was described by Kewesch (1934). Diamond (1974) observed talocalcaneal coalition in a mother and 3 of her 8 children. It is probable that this is a disorder distinct from the more common calcaneonavicular bridges.

Symptoms

Limbs: Carpal synostosis; Tarsal synostosis; Digital synostosis; Radial-head subluxation; Aplasia/hypoplasia of middle phalanges; Metacarpophalangeal synostoses; Absent phalanges; Short metacarpals

Nails: Absent nails

Nose: Hypoplastic alae nasae

Inheritance: Autosomal dominant
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Spondyloepimetaphyseal dysplasia, irapa type

Retrieved: 27-07-2015
Source: OMIM (Original article)

Clinical features

Arias et al. (1976) described a seemingly new form of skeletal dysplasia among the Irapa Indians of Venezuela. Features included short spine from platyspondyly, short metacarpals and metatarsals, and striking changes in the proximal femoral and distal humeral epiphyses.

Hernandez et al. (1980) described SEMDIT in 3 sibs from a Mexican mestizo family. Arias (1981) suggested SEMI as a simple designation.

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Short stature, disproportionate short-trunked (identifiable at birth)

CHEST: [Ribs, sternum, clavicles, and scapulae]; Widened costochondral junction; Pectus carinatum

SKELETAL: Osteoarthritis; Spondyloepimetaphyseal dysplasia; [Spine]; Platyspondyly; Small sacrum; Increased lumbar lordosis; [Pelvis]; Protruding iliac wings; Coxa vara; Wide femoral neck; [Limbs]; Short arms; Limited forearm extension; Metaphyseal dysplasia; Severe epiphyseal hypoplasia; Osteoarthritis; Arthralgias; Diaphyseal shortness; Genu valgum; [Hands]; Short metacarpals; Short, broad hands; Capitate-hamate fusion; [Feet]; Short metatarsals; Flat, broad feet; Long second toes

MISCELLANEOUS: Waddling gait
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Chondrodysplasia-pseudohermaphroditism syndrome

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

Nivelon et al. (1992) described 2 sibs with an apparently 'new' chondrodysplasia-pseudohermaphroditism syndrome. Both had severe dwarfism, antenatal in origin, with general chondrodysplasia, severe microcephaly with cerebellar vermis hypoplasia, hypoplastic iris, and coloboma of the optic disc. The first affected sib had shown intrauterine growth retardation on ultrasonography at the age of 5 months, at which time the limbs were considered to be short. The karyotype at that time was 46,XY; however, a phenotypic female was delivered at 38 weeks of gestation. The external genitalia and the internal genitalia, examined by sonography and laparotomy at the age of 14 months, were considered normal. The SRY gene, studied in 2 laboratories, was found to be normal with no deletion. The child was 3 years old at last description. The second affected pregnancy began when the first child was 2.5 years old. The karyotype was normal 46,XX. At 17 weeks of gestation, ultrasound examination showed abnormalities in the vertebral column and thereafter there were other skeletal changes prompting termination of the pregnancy. Both sibs showed narrow, bell-shaped thorax, micromelia, trapezoidal shape of vertebral bodies, abnormal clavicles, and short metacarpals and phalanges. The parents were young and nonconsanguineous.

Symptoms

Growth: Severe antenatal dwarfism

GU: Male pseudohermaphroditism

Skel: Chondrodysplasia

Head: Microcephaly

Neuro: Cerebellar vermis hypoplasia

Eyes: Iris hypoplasia; Optic disc coloboma

Thorax: Narrow, bell-shaped thorax

Limbs: Micromelia; Short metacarpals and phalanges

Radiology: Trapezoidal shaped vertebral bodies; Abnormal clavicles

Lab: 46,XY karyotype

Inheritance: ? Autosomal recessive
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Metaphyseal dysplasia without hypotrichosis

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: rmrp

This disease has been moved to Cartilage-hair hypoplasia
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Metaphyseal dysplasia without hypotrichosis

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: rmrp

Clinical features

A number sign (#) is used with this entry because of evidence that the cartilage-hair hypoplasia variant with only skeletal manifestations is due to compound heterozygous mutation in the RMRP gene (157660) on chromosome 9p13.Verloes et al. (1990) presented a series of 6 patients with skeletal changes precisely like those of cartilage-hair hypoplasia (CHH; 250250), but without hypotrichosis or immunodeficiency. Two of the patients were sibs. Microscopic examination of the hair showed a reduction in the diameter of the hair shaft. Verloes et al. (1990) suggested that this may be a form of metaphyseal dysplasia allelic to CHH.

Molecular genetics

In 2 unrelated boys with the cartilage-hair hypoplasia variant with only skeletal manifestations, Bonafe et al. (2002) identified compound heterozygous mutations (157660.0001; 157660.0009-157660.0011) in the RMRP gene that segregated with the disorder in both families. Bonafe et al. (2002) suggested that short stature and metaphyseal changes associated with cone-shaped epiphyses of the hands should raise the diagnostic possibility of a CHH-related disorder that can then be confirmed by mutation analysis.

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Disproportionate dwarfism

HEAD AND NECK: [Face]; Normal facies

SKELETAL: Joint laxity, mild; Metaphyseal dysplasia; [Spine]; Normal spine; [Pelvis]; Normal pelvis; [Limbs]; Limb shortening; Short long bones; Genu varus; Metaphyseal irregularities (distal femora, proximal and distal tibiae, distal radii and ulnae); [Hands]; Phalangeal cone-shaped epiphyses; Short metacarpals; Metacarpal/metaphyseal cupping

SKIN, NAILS, HAIR: [Hair]; Normal hair

IMMUNOLOGY: No immunodeficiency

MISCELLANEOUS: Allelic to cartilage-hair hypoplasia (250250)

MOLECULAR BASIS: Caused by mutation in the mitochondrial RNA-processing endoribonuclease gene (RMRP, 157660.0009)
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Osteochondromatosis

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Osteochondromatosis is a condition involving a proliferation of osteochondromas. Types include: Hereditary multiple exostoses Synovial osteochondromatosis
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Fibrochondrogenesis

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: col11a1, slc35d1

Fibrochondrogenesis is a rare, neonatally lethal, rhizomelic chondrodysplasia. Eleven cases have been reported. The face is distinctive and characterized by protuberant eyes, flat midface, flat small nose with anteverted nares and a small mouth with long upper lip. Cleft palate, micrognathia and bifid tongue can occur. The limbs show marked shortness of all segments with relatively normal hands and feet. No internal anomalies other than omphalocele have been reported. Transmission is probably autosomal recessive. Recurrence in a consanguineous family (affecting both sexes) and concordance of affected male twins have been reported. Expert reviewer(s) Pr Lihadh AL-GAZALI Last update: February 2005

Uncombable hair, retinal pigmentary dystrophy, dental anomalies, and brachydactyly

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

Bork et al. (1987) reported a new type of ectodermal dysplasia with congenital hypotrichosis and uncombable hair, associated with juvenile cataracts, retinal pigmentary dystrophy, oligodontia, and brachymetacarpy. The condition was inherited as an autosomal dominant. Silengo et al. (1993) reported an isolated case. They illustrated the presence of supernumerary inferior lateral incisors and microdontia. The patient was mildly retarded. Scanning electron microscopy showed the presence of longitudinal grooves giving the typical appearance of pili canaliculi. Uncombable hair occurs as an isolated trait inherited as an autosomal dominant (191480). The uncombable hair is also referred to as 'spun-glass' hair.

Symptoms

INHERITANCE: Autosomal dominant

HEAD AND NECK: [Eyes]; Retinal pigmentary dystrophy; Juvenile cataract; [Teeth]; Oligodontia; Microdontia; Supernumerary teeth

GENITOURINARY: [External genitalia, male]; Hypospadias

SKELETAL: [Hands]; Brachydactyly; Short proximal phalanges; Short metacarpals; [Feet]; Brachydactyly

SKIN, NAILS, HAIR: [Hair]; Uncombable hair; Pili canaliculi; Pili trianguli

Tricho-retino-dento-digital syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)

Tricho-retino-dento-digital syndrome is an autosomal dominant ectodermal dysplasia syndrome, characterized by uncombable hair syndrome (see this term), congenital hypotrichosis and dental abnormalities such as oligodontia (see this term) or hyperdontia, and associated with early-onset cataract, retinal pigmentary dystrophy, and brachydactyly with brachymetacarpia. Furthermore, hyperactivity and a mild intellectual deficit have been reported in affected patients. Last update: October 2013
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Brachymetapody-anodontia-hypotrichosis-albinoidism

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

Tuomaala and Haapanen (1968) described a Finnish family in which 2 sisters and a brother had an identical syndrome of congenital anodontia, small maxilla giving an impression of mandibular prognathism, short stature with particular shortening of the metacarpals and metatarsals, little hair growth, albinoidism, and multiple ocular abnormalities including strabismus, nystagmus, distichiasis, lenticular opacities, and high-grade myopia. The parents were not known to be related but came from the same parish in northeast Finland.

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Short stature

HEAD AND NECK: [Ears]; Low-set ears; [Eyes]; Downslanting palpebral fissures; Strabismus; Thin eyelashes; Distichiasis; Myopia; Irregular nystagmus; Cataract; Corneal opacities; Tarsal hypoplasia; [Teeth]; Anodontia

CHEST: [Breasts]; Small breast; Hypoplastic nipples; Unpigmented areola

GENITOURINARY: [External genitalia, female]; Hypoplastic labia

SKELETAL: [Skull]; Hypoplastic maxilla; [Hands]; Short fingers; Short metacarpals (3rd-5th); [Feet]; Short toes (2nd-5th); Short metatarsals

SKIN, NAILS, HAIR: [Skin]; Albinoidism; [Hair]; Thin hair; Absent pubic hair; Absent axillary hair; Thin eyelashes
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Oculoosteocutaneous syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)

This syndrome is characterised by congenital anodontia, a small maxilla, short stature with shortened metacarpals and metatarsals, sparse hair, albinoidism and multiple ocular anomalies. It has been described in three siblings (one brother and two sisters). Transmission is autosomal recessive. Last update: October 2006
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Brachydactyly, type e1

Retrieved: 27-07-2015
Source: OMIM (Original article)

Clinical features

A number sign (#) is used with this entry because of evidence that a skeletal malformation with features overlapping those of brachydactyly types E and D (BDD; 113200) is caused by heterozygous mutation in the HOXD13 gene (142989) on chromosome 2q31.

Another form of brachydactyly type E, BDE2 (613382), is caused by heterozygous mutation in the PTHLH gene (168470) on chromosome 12p12.1-p11.2.

Also see the hypertension and brachydactyly syndrome (112410).In type E brachydactyly, shortening of the fingers is mainly in the metacarpals and metatarsals. Wide variability in the number of digits affected occurs from person to person, even in the same family. Male-to-male transmission of type E brachydactyly has been observed (McKusick and Milch, 1964).

Hertzog (1968) suggested that there are at least 3 subtypes of BDE: E1, in which shortening is limited to fourth metacarpals and/or metatarsals (Hortling et al., 1960); E2, in which variable combinations of metacarpals are involved, with shortening also of the first and third distal and the second and fifth middle phalanges (McKusick and Milch, 1964); and E3, a dubious category which may have a variable combination of short metacarpals without phalangeal involvement.

Some individuals with BDE are moderately short of stature and have round facies but do not have ectopic calcification (or ossification), mental retardation or cataract as in pseudohypoparathyroidism (103580) which is otherwise a clinically similar entity. This phenotype occurs with a chromosomal aberration, the XO Turner syndrome. Also see brachydactyly-nystagmus-cerebellar ataxia (Biemond syndrome I), a probable dominant trait. Poznanski et al. (1977) concluded that 'brachydactyly E is indistinguishable radiologically from the PHP-PPHP syndrome'.

Newcombe and Keats (1969) described an extensively affected kindred with a dominant pedigree pattern (their pedigree II) as having peripheral dysostosis. The description resembled that in the family of McKusick and Milch (1964) except for cone epiphyses. The authors thought that the presence of cone epiphyses in their family was a distinguishing feature.

In a family reported by Gorlin and Sedano (1971), type E brachydactyly was associated with multiple impacted teeth. Gorlin and Sedano (1971) gave the designation 'cryptodontic metacarpalia' to type E brachydactyly associated with multiple impacted teeth. The clavicles were unusually straight and short. Whether this is a distinct entity is not clear.

Cytogenetics

Wilson et al. (1995) found a cytogenetically visible de novo deletion of 2q37 in 4 patients in whom brachydactyly type E was combined with mental retardation to ...

Symptoms

Growth: Moderately short stature

Limbs: Brachydactyly; Short metacarpals; Variable short metatarsals

Facies: Round facies

Teeth: Multiple impacted teeth

Skel: Straight and short clavicles

Radiology: Radiologically indistinguishable from the PHP-PPHP syndrome

Inheritance: Autosomal dominant
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Fitzsimmons-guilbert syndrome

Retrieved: 27-07-2015
Source: OMIM (Original article)

Clinical features

Fitzsimmons and Guilbert (1987) described male uniovular twins, aged 20 years, who had had slowly progressive spastic paraplegia from early in life. Both had skeletal abnormalities of the hands and feet: brachydactyly, cone-shaped epiphyses, and an abnormal metaphyseal-phalangeal pattern profile. In addition, they had nonspecific dysarthria and low-normal intellectual capacity. The brachydactyly appears to have been type E (113300). The mode of inheritance was uncertain.

Hennekam (1994) reported a girl with slowly progressive difficulties in walking, dysarthria, growth retardation, brachydactyly, and cone-shaped epiphyses, and suggested the eponym Fitzsimmons syndrome. Lacassie et al. (1999) reported monozygotic female twins, aged 62 years, with mental retardation, dysarthria, progressive spastic paraplegia, and brachydactyly type E who had been institutionalized since age 33 years. Differences from the patients reported by Fitzsimmons and Guilbert (1987) included more severe mental retardation and a different metacarpal-phalangeal pattern profile, suggesting either an expanded phenotype of the Fitzsimmons-Guilbert syndrome or a different entity.

Armour et al. (2009) reported a 15-year-old boy with features consistent with Fitzsimmons syndrome. He began toe walking at age 18 months, which progressed to spastic paraparesis by age 4 years, with increased lower limb muscle tone and bilateral extensor plantar responses. Limb contractures and frank spastic gait developed later. He also had dysfunctional bladder voiding with nocturnal enuresis. Global developmental delay became apparent at age 12 months and continued throughout childhood. Physical examination at age 15 years showed microcephaly and small hands and feet with marked brachydactyly, particularly of the second and fifth fingers. Thumbs and big toes were short and broad. Radiographs showed short metacarp...

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Short stature (less than 3rd percentile); [Weight]; Weight less than 3rd percentile

HEAD AND NECK: [Face]; Narrow face; Mid-face hypoplasia; [Mouth]; High palate

CHEST: [Ribs, sternum, clavicles, and scapulae]; Pectus excavatum; Pectus carinatum

ABDOMEN: [Gastrointestinal]; Feeding problems

GENITOURINARY: [Bladder]; Dysfunctional voiding; Nocturnal enuresis; Bladder instability

SKELETAL: [Hands]; Brachydactyly; Broad thumbs; Cone-shaped epiphyses; Short metacarpals; Short phalanges; [Feet]; Brachydactyly; Pes planus; Broad halluces; Short metatarsals; Short phalanges; Cone-shaped epiphyses

NEUROLOGIC: [Central nervous system]; Global developmental delay; Cognitive impairment; Slowly progressive spastic paraplegia; Scissors gait; Hyperreflexia; Extensor plantar responses

VOICE: Dysarthria; Hypernasal speech

MISCELLANEOUS: Onset of progressive spastic paraplegia in childhood
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Kyphomelic dysplasia

Retrieved: 27-07-2015
Source: GARD (Original article)
Associated genes: sox9

Kyphomelic dysplasia

Kyphomelic dysplasia is a prenatal skeletal disease that causes dwarfism characterized by the following: a disproportionately short stature with a short narrow chest, shortening and bending (bowing) of the limbs, flared irregular metaphyses of the bones, and characteristic facial features.  Bone changes are said to improve with age. Kyphomelic dysplasia is inherited in an autosomal recessive pattern.    Recent studies indicate that Kyphomelic dysplasia is no longer considered it's own entity and that individual cases should be further evaluated and re-classified as another existing chondrodysplasias, such as Schwartz-Jampel syndrome
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Pelger-Huet anomaly

Retrieved: 27-07-2015
Source: GARD (Original article)
Associated genes: lbr, mad2l1bp, kif1b, sgcg, nbas

Pelger-Huet anomaly

Pelger-Huët anomaly (PHA) is an inherited blood condition in which the nuclei of several types of white blood cells (neutrophils and eosinophils) have unusual shape (bilobed, peanut or dumbbell-shaped instead of the normal trilobed shape) and unusual structure (coarse and lumpy).  Click here to view a picture of these cells seen under the microscope. PHA is caused by a mutation or alteration in a gene called the lamin B receptor (LBR) gene located on the long arm of chromosome 1 (1q42.1). It is important to distinguish this autosomal dominant disorder from acquired or pseudo-Pelger-Huët anomaly, which may be found in individuals with certain types of leukemia or myelodysplastic syndromes
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Pelger-Huet anomaly

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Associated genes: lbr, mad2l1bp, kif1b, sgcg, nbas
Pelger-Huët anomaly (pronunciation: [pel′gər hyo̅o̅′ət]) is a blood laminopathy associated with the lamin B receptor. It is characterized by a white blood cell type known as a neutrophil whose nucleus is hyposegmented.

It is a genetic disorder with an autosomal dominant inheritance pattern. Heterozygotes are clinically normal, although their neutrophils may be mistaken for immature cells which may cause mistreatment in a clinical setting. Homozygotes tend to have neutrophils with rounded nuclei that do have some functional problems.

Congenital Pelger-Huet anomaly

Is a benign dominantly inherited defect of terminal neutrophil differentiation secondary to mutations in the lamin B receptor (LBR) gene. The characteristic leukocyte appearance was first reported in 1928 by Pelger, a Dutch hematologist, who described leukocytes with dumbbell-shaped bilobed nuclei, a reduced number of nuclear segments, and coarse clumping of the nuclear chromatin. In 1931 Huet, a pediatrician, identified it as an inherited disorder.Cunningham JM, Patnaik MM, Hammerschmidt DE, Vercellotti GM. Historical perspective and clinical implications of the Pelger-Hüet cell. Am J Hematol. Feb 2009;84(2):116-9 It is a genetic disorder with an autosomal dominant inheritance pattern.Hoffmann K, Dreger CK, Olins AL, et al. Mutations in the gene encoding the lamin B receptor produce an altered nuclear morphology in granulocytes (Pelger-Huët anomaly). Nat Genet. Aug 2002;31(4):410-4.Vale AM, Tomaz KLR, Sousa RS, Soto-Blanco B. Pelger-Huët anomaly in two related mixed-breed dogs. J Vet Diag Invest. Jul 2011;23(4):863-5. |doi=10.1177/1040638711407891 Heterozygotes are clinically normal, although their neutrophils may be mistaken for immature cells, which may cause mistreatment in a clinical setting. Homozygotes tend to have neutrophils with rounded nuclei that do have some functional problems. Homozygous individuals inconsistently have skeletal anomalies such as post-axial polydactyly, short metacarpals, short upper limbs, short stature, or hyperkyphosis. Identifying Pelger-Huët anomaly (PHA)is important to differentiate from bandemia with a left-shifted peripheral blood smear and neutrophilic band forms and from an increase in young neutrophilic forms that can be observed in association with infection.

Acquired or Pseudo-Pelger-Huet anomaly

Anomalies resembling Pelger-Huët anomaly that are acquired rather than congenital have been described as pseudo Pelger-Huët anomaly. These can develop in the course of acute myelogenous leukemia or chronic myelogenous leukemia and in myelodysplastic syndrome. In patients with these conditions, the pseudo–Pelger-Huët cells tend to appear late in the disease and often appear after considerable chemotherapy has been administered. The morphologic changes have also been described in myxedema associated with panhypopituitarism, vitamin B-12 and folate deficiency, multiple myeloma, enteroviral infections, malaria, muscular dystrophy, leukemoid reaction secondar...
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Pacman dysplasia

Retrieved: 27-07-2015
Source: Orphanet (Original article)

This syndrome is characterized by epiphyseal stippling and osteoclastic overactivity. It has been described in less than 10 patients but may be underdiagnosed. It is characterized radiographically by severe stippling of the lower spine and long bones, and periosteal cloaking. Patients also have short metacarpals. The syndrome may be inherited as an autosomal recessive trait. This disorder should be included in the differential diagnosis of mucolipidosis type II. In order to make a definitive diagnosis, lysosomal storage should be investigated by electron microscopy, or enzyme assays should be performed. Familial recurrence can be easily detected by prenatal ultrasonography. This skeletal dysplasia is lethal. Last update: February 2007
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Brachymetatarsus iv

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

Before his death on December 1, 1964, J. B. S. Haldane, with A. K. Ray, prepared a paper describing short fourth metatarsus resulting in unilateral or bilateral short fourth toes identified in 206 persons in Northeastern India (Ray and Haldane, 1965). This was Haldane's only publication in an American journal (Ray, 1989). From a study of 61 pedigrees Ray and Haldane (1965) concluded that the trait is autosomal dominant with approximately 27% penetrance. The wearing of sandals facilitated the population survey. In an initial survey they found the trait in 3 unrelated men among 2,500 in Orissa. Although short terminal phalanx of the thumb was found in 3 of 117 persons with short fourth toes, 2 bilateral and 1 unilateral, there was apparently no instance of short metacarpals, thus indicating that the trait is distinct from type E brachydactyly (113300).

Symptoms

Limbs: Short fourth metatarsus; Short fourth toes

Inheritance: Autosomal dominant
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Metaphyseal chondrodysplasia, kaitila type

Retrieved: 27-07-2015
Source: OMIM (Original article)

Clinical features

Kaitila et al. (1982) described a brother and sister with a previously unrecognized form of disproportionate short stature. The brother had tracheobronchial malacia and progressive scoliosis. The trachea and bronchi were reinforced with surrounding acrylate mesh before surgical treatment of the scoliosis. (Tracheobronchial malacia occurs in infants with chondrodysplasias, e.g., diastrophic dysplasia (222600), but is rare in adults with skeletal dysplasias. Bronchomalacia occurs as an apparently isolated genetic disorder (211450).) The sister was less severely affected. Bone x-rays showed progression from marked metaphyseal dysplasia of tubular bones in childhood to short and broad bones with mild dysplasia of the joints in adulthood. The vertebrae and intervertebral plates were only mildly affected, despite marked scoliosis. Cartilage-hair hypoplasia (250250), a relatively frequent disorder in Finland, was carefully ruled out. Possibly the sibs represent a genetic compound of the CHH gene and another allele.

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Short stature, disproportionate short-limb

HEAD AND NECK: [Nose]; Narrow, beaked nose; [Mouth]; Narrow palate

RESPIRATORY: [Airways]; Tracheobronchial malacia

CHEST: [External features]; Shallow, narrow chest

SKELETAL: Metaphyseal dysplasia; [Spine]; Progressive scoliosis; Thoracolumbar scoliosis; [Pelvis]; Small iliac bones; Irregular proximal femoral metaphyses; Delayed ossification proximal femoral epiphyses; [Limbs]; Short limbs; Limited elbow extension; Enlarged joints; Short, broad tibiae and fibulae; Irregular, widened metaphyses; [Hands]; Short fingers; Finger joint hypermobility; Short phalanges (especially distal phalanges); Short metacarpals; Cone-shaped epiphyses; [Feet]; Short phalanges; Short metatarsals

SKIN, NAILS, HAIR: [Skin]; Wrinkled skin over fingers; [Nails]; Short, broad nails

NEUROLOGIC: [Central nervous system]; Delayed motor development; Normal intelligence
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Dyggve-melchior-clausen syndrome, x-linked

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

Yunis et al. (1980) described a Colombian family in which 10 males in 3 generations, in a typical X-linked recessive pedigree pattern, had the Dyggve-Melchior-Clausen syndrome. The affected males varied in age from 13 to 15 years. Normal intelligence was another difference from the autosomal recessive form. The authors cited some reported families that are equally consistent with X-linked or autosomal recessive inheritance (223800). Spranger (1981) suggested that the disorder described by Yunis et al. (1980) was in fact X-linked SED tarda (313400).

Symptoms

INHERITANCE: X-linked recessive

GROWTH: [Height]; Short stature, disproportionate (short trunk)

HEAD AND NECK: [Head]; Brachycephaly; Normal head circumference; [Face]; Coarse face; Prognathism; [Neck]; Short neck

CHEST: [External features]; Barrel chest; [Ribs, sternum, clavicles, and scapulae]; Sternal protrusion

SKELETAL: Restricted joint mobility (shoulders, elbows, hips); Spondyloepimetaphyseal dysplasia; [Skull]; Calvarial thickening (parietal and occipital area); Marked pneumatization of paranasal sinuses; [Spine]; Scoliosis; Pronounced lumbar lordosis; Thoracic kyphosis; Platyspondyly; Hypoplastic sacrum; [Pelvis]; Small pelvis; Small ilium; Hypoplastic ischii; Short femoral neck; Irregular iliac crest; Coxa vara; Coxa plana; [Limbs]; Genu valgum; Narrow joint spaces; Hypoplastic distal ulna; [Hands]; Small carpals; Short metacarpals; Cone-shaped epiphyses; [Feet]; Hallux valgus

NEUROLOGIC: [Central nervous system]; Normal intelligence

MISCELLANEOUS: See also Dyggve-Melchior-Clausen disease (223800)
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Roifman-chitayat syndrome

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: cyp11b2, rchts

Clinical features

Roifman and Chitayat (2009) reported 2 sisters, born to second-cousin parents, with a syndrome characterized by combined immunodeficiency, facial dysmorphism, optic atrophy, myoclonic seizures, skeletal anomalies, and developmental delay. Both patients had repeated bacterial, viral, and fungal infections consistent with combined immunodeficiency. Evaluation of the immune system revealed depressed responses to mitogens or anti-CD3 antibody. Humoral immunity was also affected as both patients failed to mount an antibody response to vaccination.

Inheritance

Roifman and Chitayat (2009) suggested autosomal recessive inheritance for this disorder because of its occurrence in female sibs of consanguineous parents.

Mapping

By linkage analysis, Roifman and Chitayat (2009) identified maximum lod scores for the disorder in their family to chromosomes 1 and 15 (maximum lod score of 2.654). The disease locus was mapped either to a 14-cm interval between SNPs dbSNP rs11583804 and dbSNP rs11806366 on chromosome 1p36.23-p33, or to a 37-cm interval between SNPs dbSNP rs2732029 and dbSNP rs815198 on chromosome 15q11-q21.1.

Symptoms

INHERITANCE: Autosomal recessive

HEAD AND NECK: [Face]; Hypoplastic supraorbital ridges; Square chin; [Eyes]; Lacrimal duct stenosis; Thin optic nerves; Puffy and droopy eyelids; Hypertelorism; [Nose]; Flat nasal bridge; Broad nasal root; [Mouth]; Thin lower lip; [Neck]; Short neck

CARDIOVASCULAR: [Vascular]; Aberrant subclavian artery

RESPIRATORY: [Airways]; Pneumonia

CHEST: [Breast]; Laterally displaced nipples

ABDOMEN: [External features]; Umbilical hernia; [Gastrointestinal]; Esophageal dyskinesia

GENITOURINARY: [Kidneys]; Cross-fused renal ectopia

SKELETAL: Osteopenia; Cone-shaped epiphyses; [Hands]; Short metacarpals; [Feet]; Short metatarsals

NEUROLOGIC: [Central nervous system]; Myoclonic seizures; Developmental delay; Dilated ventricles

IMMUNOLOGY: Repeated invasive infections; Arthritis; Normal or elevated lymphocytes; Low T-cell function; Low IgG with antibody deficiency

MISCELLANEOUS: One family with 2 sisters have been reported (as of March 2010)
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Brachydactyly, type e2

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: pthlh

Molecular genetics

A number sign (#) is used with this entry because this form of brachydactyly type E (BDE2) is caused by heterozygous mutation in the PTHLH gene (168470) on chromosome 12p.

For a general phenotypic description and a discussion of genetic heterogeneity of BDE, see BDE1 (113300).In affected members of a 3-generation family segregating autosomal dominant brachydactyly type E, short stature, and learning difficulties, Klopocki et al. (2010) performed array-based CGH and identified a 907.68-kb microdeletion on chromosome 12p that encompassed 6 known genes, only 1 of which, PTHLH (168470), was known to play a critical role in skeletal development. Klopocki et al. (2010) analyzed the PTHLH gene in 4 unrelated families with BDE and short stature and identified heterozygous missense and nonsense mutations (168470.0001-168470.0004, respectively). None of the affected individuals in the latter 4 families had learning disabilities, suggesting that the deletion of the 5 genes distal to PTHLH most likely accounted for the additional phenotype. Of the 13 total affected individuals, 10 had short stature and 3 were in the normal range. In 2 of the 5 families, affected individuals also had abnormalities of tooth development.

Cytogenetics

In a family with brachydactyly type E (BDE), Maass et al. (2010) identified a t(8;12)(q13;p11.2) translocation with breakpoints upstream of PTHLH on chromosome 12p11.2 and a disrupted KCNB2 (607738) on 8q13. Sequencing of the breakpoints identified a highly conserved activator protein-1 (AP1; see JUN, 165160) motif on 12p11.2, together with a C-ets-1 motif translocated from 8q13. AP1 and C-ets-1 bound in vitro and in vivo at the derivative chromosome 8 breakpoint, but were differently enriched between the wildtype and breakpoint allele. In chondrogenic cells from differentiated fibroblasts from BDE patients, PTHLH and its target genes, ADAMTS7 (605009) and ADAMTS12 (606184), were downregulated along with impaired chondrogenic differentiation. In human and murine chondrocytes, the AP1 motif stimulated PTHLH promoter activity whereas the derivative chromosome 8 breakpoint or C-ets-1 decreased PTHLH promoter activity.

Symptoms

INHERITANCE: Autosomal dominant

GROWTH: [Height]; Short stature

HEAD AND NECK: [Teeth]; Delayed eruption, primary and secondary (in some patients); Oligodontia (in some patients)

SKELETAL: [Hands]; Short metacarpals, III-V; [Feet]; Short metatarsals

MOLECULAR BASIS: Caused by mutation in the parathyroid hormone-like hormone gene (PTHLH, 168470.0001)
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Perlman syndrome

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: dis3l2, gpc4, gpc3, dis3

Description

A number sign (#) is used with this entry because of evidence that Perlman syndrome is caused by homozygous or compound heterozygous mutation in the DIS3L2 gene (614184) on chromosome 2q37.2.Perlman syndrome is an autosomal recessive congenital overgrowth syndrome with similarities to Beckwith-Wiedemann syndrome (BWS; 130650). Affected children are large at birth, are hypotonic, and show organomegaly, characteristic facial dysmorphisms (inverted V-shaped upper lip, prominent forehead, deep-set eyes, broad and flat nasal bridge, and low-set ears), renal anomalies (nephromegaly and hydronephrosis), frequent neurodevelopmental delay, and high neonatal mortality. Perlman syndrome is associated with a high risk of Wilms tumor, with a 64% incidence in infants surviving beyond the neonatal period. The tumor is diagnosed at an earlier age in these individuals compared with sporadic cases (less than 2 years and 3-4 years of age, respectively), and there is a high frequency of bilateral tumors (55%). Histologic examination of the kidneys in children with Perlman syndrome shows frequent nephroblastomatosis, which is a precursor lesion for Wilms tumor (summary by Astuti et al., 2012).

Clinical features

Liban and Kozenitzky (1970) and Perlman et al. (1973) described 5 offspring, of Jewish-Yemenite second-cousin parents, with a disorder manifested by large birth size, bilateral renal hamartomas with or without nephroblastomatosis, hypertrophy of the islets of Langerhans, and unusual facies. The longest survival was 27 days. There are some obvious similarities to the Beckwith-Wiedemann syndrome (130650) but the facies is thought to be characteristic with depre...

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Other]; Large birth size; Macrosomia

HEAD AND NECK: [Face]; Unusual facies; Round facial fullness; Micrognathia; [Ears]; Low-set ears; [Nose]; Depressed nasal bridge; Broad nasal bridge; [Mouth]; Anteverted upper lip; Open mouth; Long upper lip; Inverted V-shaped upper lip

CARDIOVASCULAR: [Vascular]; Interrupted aortic arch

CHEST: [Diaphragm]; Diaphragmatic hernia

ABDOMEN: [External features]; Abdominal muscular hypoplasia; Visceromegaly; [Pancreas]; Islets of Langerhans hypertrophy; [Gastrointestinal]; Volvulus; Distal ileal atresia

GENITOURINARY: [External genitalia, male]; Cryptorchidism; [Kidneys]; Bilateral renal hamartomas; Nephroblastomatosis; Wilms tumor

SKIN, NAILS, HAIR: [Hair]; Upsweep of anterior scalp hair

NEUROLOGIC: [Central nervous system]; Corpus callosum agenesis; Developmental delay

ENDOCRINE FEATURES: Hyperinsulinism

PRENATAL MANIFESTATIONS: Fetal ascites without hydrops; [Amniotic fluid]; Polyhydramnios

MISCELLANEOUS: Fatal in the neonatal period (in some patients)

MOLECULAR BASIS: Caused by mutation in the Dis3 mitotic control, S. cerevisiae, homolog-like 2 gene (DIS3L2, 614184.0001)
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Perlman syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: dis3l2, gpc4, gpc3, dis3

Perlman syndrome is characterized principally by polyhydramnios, neonatal macrosomia, bilateral renal tumours (hamartomas with or without nephroblastomatosis), hypertrophy of the islets of Langerhans and facial dysmorphism. So far, about 30 patients have been reported in the literature. The facial dysmorphism is considered as characteristic with upsweeping anterior scalp hair, a depressed nasal bridge, hypotonic appearance with an open mouth, a prominent everted upper lip, and mild micrognathia. Agenesis of the corpus callosum, choroid plexus haemangiomas, cleft palate, dextroposition of the heart, interrupted aortic arch, diaphragmatic hernia, visceromegaly including nephromegaly, hepatomegaly, cardiomegaly, thymus hyperplasia, hepatic fibrosis with porto-portal bridging, abdominal muscular hypoplasia, distal ileal atresia, and cryptorchidism were also described in some patients and maybe components of this syndrome. Hyperinsulinism appears to be an important feature of this disease and may be a preventable cause of death. The syndrome appears to be inherited in an autosomal recessive manner. The principle differential diagnoses are the Beckwith-Wiedemann (BWS) and Simpson-Golabi-Behmel syndromes (see these terms): mutations the GPC3 gene were excluded as being causative anomalies in several publications and genetic or epigenetic alterations of the 11p15 region (involved in BWS) have never been reported in patients with Perlman syndrome, despite the strong phenotypic similarities between the two syndromes. Prenatal diagnosis may be oriented by ultrasonography searching for macroglossia and renal anomalies (cysts or hypertrophy). Management is supportive and should be multidisciplinary. The prognosis for Perlman syndrome is poor with a high mortality rate, especially in the neonatal period, due to sepsis or progressive respiratory insufficiency. Among the infants who survived beyond the neonatal period, two thirds developed a Wilms' tumor and most had some ...
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GM1 gangliosidoses

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Associated genes: glb1
The GM1 gangliosidoses are caused by a deficiency of beta-galactosidase, with resulting abnormal storage of acidic lipid materials in cells of the central and peripheral nervous systems, but particularly in the nerve cells.

Types

GM1 has three forms: early infantile, late infantile, and adult.

Early infantile GM1

Symptoms of early infantile GM1 (the most severe subtype, with onset shortly after birth) may include neurodegeneration, seizures, liver (hepatomegaly) and spleen (splenomegaly) enlargement, coarsening of facial features, skeletal irregularities, joint stiffness, distended abdomen, muscle weakness, exaggerated startle response to sound, and problems with gait. About half of affected patients develop cherry-red spots in the eye. Children may be deaf and blind by age 1 and often die by age 3 from cardiac complications or pneumonia. Autosomal recessive disorder; beta-galactosidase deficiency; neuronal storage of GM1 ganglioside and visceral storage of galactosyl oligosaccharides and keratan sulfate. Early psychomotor deterioration: decreased activity and lethargy in the first weeks; never sit; feeding problems - failure to thrive; visual failure (nystagmus noted) by 6 months; initial hypotonia; later spasticity with pyramidal signs; secondary microcephaly develops; decerebrate rigidity by 1 year and death by age 1–2 years (due to pneumonia and respiratory failure); some have hyperacusis. Macular cherry-red spots in 50% by 6–10 months; corneal opacities in some Facial dysmorphology: frontal bossing, wide nasal bridge, facial edema (puffy eyelids); peripheral edema, epicanthus, long upper lip, microretrognathia, gingival hypertrophy (thick alveolar ridges), macroglossia Hepatomegaly by 6 months and splenomegaly later; some have cardiac failure Skeletal deformities: flexion contractures noted by 3 months; early subperiosteal bone formation (may be present at birth); diaphyseal widening later; demineralization; thoracolumbar vertebral hypoplasia and beaking at age 3–6 months; kyphoscoliosis. Dysostosis multiplex (as in the mucopolysaccharidoses). 10-80% of peripheral lymphocytes are vacuolated; foamy histiocytes in bone marrow; visceral mucopolysaccharide storage similar to that in Hurler disease; GM1 storage in cerebral gray matter is 10 fold elevated (20-50-fold increased in viscera) Galactose-containing oligosacchariduria and moderate keratan sulfaturia Morquio disease Type B: Mutations with higher residual beta-galactosidase activity for the GM1 substrate than for keratan sulfate and other galactose-containing oligosaccharides have minimal neurologic involvement but severe dysostosis resembling Morquio disease type A (Mucopolysaccharidosis type 4). Adapted from Lyon GL et al., Neurology of Hereditary Metabolic Diseases of Children, ed 2, 1996, p53-55

Late infantile GM1

Onset of late infantile GM1 is typically between ages 1 and 3 years. Neurological symptoms include ataxia, seizures, dementia, and difficulties wit...
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Renal dysplasia-limb defects syndrome

Retrieved: 27-07-2015
Source: OMIM (Original article)
Renal dysplasia-limb defects syndrome

Description

Schrander-Stumpel et al. (1990) described newborn brother and sister who died shortly after birth from respiratory failure. They showed growth retardation with a Potter-like face, complete phocomelia of the upper limbs, severe hypoplasia of the 6 upper ribs, renal dysplasia and abnormalities of the external genitalia. They suggested that these cases represent the same entity reported by Ulbright et al. (1984). The syndrome appears to be lethal because of severe renal dysplasia which causes oligohydramnios and pulmonary hypoplasia. Schrander-Stumpel et al. (1990) suggested the designations 'renal dysplasia--limb defects syndrome (RL syndrome).'

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Birth length below 5th percentile; [Weight]; Birth weight below 5th percentile; [Other]; Intrauterine growth retardation (IUGR)

HEAD AND NECK: [Head]; Prominent occiput; [Face]; Micrognathia; 'Potter-like' facies; [Ears]; Low-set ears; Dysplastic ears; [Nose]; Depressed nasal root; Beaked nose; [Mouth]; Small mouth; High palate; Long-tented upper lip; Thin vermilion borders; [Neck]; Short neck

RESPIRATORY: Respiratory distress; Respiratory failure; [Lung]; Hypoplastic lungs; Pneumothorax

CHEST: [Ribs, sternum, clavicles, and scapulae]; Short sternum; Long, thin ribs; Hypoplastic ribs

GENITOURINARY: [External genitalia, male]; Circumferential penile groove; [External genitalia, female]; Prominent labia minora; Hypertrophic clitoris; [Internal genitalia, male]; Cryptorchidism; [Kidneys]; Renal hypoplasia

SKELETAL: [Spine]; Anterior rounding of lumbar vertebrae; [Pelvis]; Wide alar wing; [Limbs]; Short forearms; Phocomelia; Absent ulnae; Aplastic-hypoplastic radius; Aplastic humeri; Absent fibulae; Thin legs; Humeroradial fusion; [Hands]; Short metacarpals; [Feet]; Talipes equinovarus

PRENATAL MANIFESTATIONS: [Amniotic fluid]; Oligohydramnios; [Placenta and umbilical cord]; Single umbilical artery; [Maternal]; Gestational diabetes

MISCELLANEOUS: Neonatal death
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Short-rib thoracic dysplasia 2 with or without polydactyly

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: ift80

Description

A number sign (#) is used with this entry because short-rib thoracic dystrophy-2 with or without polydactyly (SRTD2) is caused by homozygous mutation in the IFT80 gene (611177) on chromosome 3q25.Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013).

There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330).

For a discussion of genetic heterogeneity of short-rib thoracic dysplasia, see SRTD1 (208500).

Clinical features

Beales et al. (2007) reported 3 consanguineous families with a form of asphyxiating thoracic dystrophy: 2 families were from Pakistan and 1 was from Turkey. The Turkish child had a narrow chest, short femora, and postaxial polydactyly on the hands and feet. One of the Pakistani families had 2 affected children. One child had short femora, narrow chest, and brachydactyly with broad hands and small feet. Skeletal survey showed trident acetabular roofs, mild bowing of the femurs, and small middle phalanges. The second child in this family had short femora, narrow chest, and rhizomelic limb shortening. Neither child had internal organ abnormalities or neonatal respiratory problems. The proband in the second Pakistani family was born stillborn at 20 weeks' gestation due to chorioamnionitis. Autoradiography showed mesomelic shortening of the lower limb with curved femora and trident acetabular roofs. There was no polydactyly, but the hands had short middle phalanges and meta...

Symptoms

INHERITANCE: Autosomal recessive

CHEST: [External features]; Narrow thorax

SKELETAL: [Limbs]; Short femora; Bowed femora; Mesomelic limb shortening; Rhizomelic limb shortening; Trident acetabular roofs; [Hands]; Polydactyly, postaxial; Brachydactyly; Short metacarpals; Broad hands; [Feet]; Polydactyly, postaxial; Small feet

MOLECULAR BASIS: Caused by mutation in the homolog of the chlamydomonas intraflagellar transport 80 gene (IFT80, 611177.0001)
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Chondrodysplasia with joint dislocations, gpapp type

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: impad1

Clinical features

A number sign (#) is used with this entry because the GPAPP type of chondrodysplasia with joint dislocations is caused by homozygous mutation in the IMPAD1 gene (614010) on chromosome 8q12.Vissers et al. (2011) reported 4 individuals with a distinct condition characterized by short stature, chondrodysplasia with brachydactyly, congenital joint dislocations, micrognathia, cleft palate, and facial dysmorphism. Three patients, a German girl and Turkish sisters, were from consanguineous families, and the fourth patient was born to healthy parents from Kerala, India.

Nizon et al. (2012) described 2 unrelated Turkish patients with a Catel-Manzke syndrome (616145)-like phenotype, 1 of whom was a male infant originally reported by Kiper et al. (2011), in whom they identified homozygous loss-of-function mutations in the IMPAD1 gene. The patients had severe growth retardation with short and abnormal extremities, cleft palate with micrognathia, and knee hyperlaxity. Radiographs of hands and feet revealed numerous accessory bones with abnormally shaped phalanges and carpal synostosis. Nizon et al. (2012) noted that in contrast to previously reported patients with IMPAD1 mutations who had recurrent joint dislocations, these patients had only knee hyperlaxity.

Inheritance

Kiper et al. (2011) reported a male infant, born to consanguineous Turkish parents, with classic features of Catel-Manzke syndrome (616145) as well as ligamentous laxity in the knees. Two previously born female sibs of the patient, one of whom died at birth and the other at postnatal day 13, also had features of the syndrome. Consanguinity and possibly affected sibs led the authors to suggest autosomal recessive inheritance.

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Short stature; [Other]; Prenatal growth delay

HEAD AND NECK: [Head]; High forehead; [Face]; Flat face; [Ears]; Hearing loss; [Eyes]; Prominent eyes; [Nose]; Broad nasal root; Small nose; [Mouth]; Micrognathia; Small mouth; Posterior cleft palate

SKELETAL: [Skull]; Coronal craniosynostosis; [Spine]; Reduction of the intervertebral spaces; [Pelvis]; Dysplasia of the hip acetabulum; [Limbs]; Shortening and deformity of the limbs; Patellar dislocation; Limited supination of the elbow; Genua valga; Dysplasia of the proximal femoral epiphyses; Subluxation of the radial heads; [Hands]; Brachydactyly; Hitch-hiker appearance of the thumb; Short metacarpals; Irregular size of the metacarpal epiphyses; Supernumerary carpal ossification centers; Longitudinal splitting of the proximal phalanx of forefinger; Fusion of the capitate and hamate bones; Splitting of the first metacarpal in two parts; [Feet]; Adducted feet; Short feet; Short toes; Lateral deviation of the fifth toe

MOLECULAR BASIS: Caused by mutation in the inositol monophosphatase domain-containing protein 1 gene (IMPAD1, 614010.0001)

Nicolaides–Baraitser syndrome

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Nicolaides–Baraitser syndrome (NBS) is a rare condition which has only been reported in 23 cases worldwide. NBS is a distinct condition and well recognizable once the symptoms have been identified, and has probably been underdiagnosed until now.

Symptoms

The most common symptoms of Nicolaides–Baraitser syndrome are severe mental retardation with absent or limited speech, seizures, short stature, sparse hair, typical facial characteristics, brachydactyly, and prominent finger joints and broad distal phalanges.

Major Features of Nicolaides–Baraitser Syndrome

Mild prenatal growth retardation Moderate postnatal growth retardation Severe developmental delay Severely impaired speech Seizures Microcephaly Sparse hair Progressive skin wrinkling Thick, anteverted alae nasi Long and broad philtrum Large mouth Thin upper and thick lower vermilion Progressive prominence of distal phalanges Progressive prominence of inter-phalangeal joints Short metacarpals–metatarsals

Naming

Paola Nicolaides was a pediatric neurologist and Michael Baraitser a clinical geneticist, both working in Great Ormond Street Hospital for Children in London. They saw a young girl with an unusual combination of signs and symptoms, thought this to be a recognizable entity. They published this in a medical journal in 1993. Other authors have suggested later on to name the entity after the two authors that described the entity first.

External links

Nicolaides–Baraitser syndrome :Delineation phenotype Paola Nicolaides and Michael Baraitser Facebook support group
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Plantar lipomatosis, unusual facies, and developmental delay

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

Pierpont syndrome is a multiple congenital anomaly syndrome associated with learning disability. Key features include distinctive facial characteristics, especially when smiling, plantar fat pads, and other limb anomalies (summary by Burkitt Wright et al., 2011).

Clinical features

Pierpont et al. (1998) suggested that 2 unrelated boys suffered from a previously undescribed disorder characterized by global developmental delay and a phenotype of microcephaly, midface hypoplasia, enlarged fleshy ears, depressed nasal bridge, anteverted nostrils, central palatal ridge, and high forehead. Bilateral congenital fat pads were present anteromedial to the heels. Fetal finger and toe pads were also present and palmar and plantar grooves were deeper than normal with 'pillowing' of the areas between the grooves. Congenital fatty heel pads, which have been described as an isolated clinical finding (Livingstone and Burd, 1995), are rare.

Oudesluijs et al. (2005) reported a 2.5-year-old boy with axial hypotonia in the first few months of life, prolonged feeding problems, moderate developmental delay, no speech development, deep palmar and plantar grooves, and fat pads at the anteromedial aspect of the heels. Examination at 7 months of age revealed a distinct facial phenotype, with high forehead, high...

Symptoms

INHERITANCE: Autosomal dominant

GROWTH: [Height]; Less than tenth centile; [Weight]; Less than fiftieth centile; [Other]; Failure to thrive (in some patients)

HEAD AND NECK: [Head]; Brachycephaly; Microcephaly; [Face]; Broad face; High forehead; High anterior hairline; Midface hypoplasia; Full cheeks; Broad, flat philtrum; [Ears]; Fleshy ears; Posteriorly rotated ears; [Eyes]; Short and narrow palpebral fissures; Hypertelorism or telecanthus; Deep-set eyes; Strabismus (in some patients); [Nose]; Short, broad nose; [Mouth]; Long upper lip with thin vermilion border; Everted lower lip; Central palatal ridge (in some patients); [Teeth]; Widely spaced teeth; [Neck]; Short neck

CHEST: [External features]; Widely spaced nipples; Hypoplastic areolae

ABDOMEN: [Gastrointestinal]; Feeding difficulties (in some patients)

GENITOURINARY: [External genitalia, male]; Small penis (in some patients)

SKELETAL: [Spine]; Scoliosis, progressive (in some patients); [Limbs]; Fat pads anterior to calcanei; [Hands]; Deep creases on palms, with pillowing in between; Fetal finger pads; Short, broad hands; [Feet]; Deep grooves on soles, with pillowing in between; Fetal toe pads; Short, broad feet

SKIN, NAILS, HAIR: [Hair]; High anterior hairline

NEUROLOGIC: [Central nervous system]; Global developmental delay; Speech delay; Seizures (in some patients); [Peripheral nervous system]; Hypotonia, truncal; Hypertonia (in some patients)

MISCELLANEOUS: Fat pads become less prominent with time
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Larsen syndrome

Retrieved: 27-07-2015
Source: GARD (Original article)
Associated genes: flnb, tgfbr2, dnm2
Larsen syndrome

Larsen syndrome

Larsen syndrome is a condition that causes abnormal development of the bones. Signs and symptoms may include clubfoot and numerous joint dislocations at birth (affecting the hips, knees and elbows); flexible joints; and a distinctive appearance of the face, hands and feet. Larsen syndrome is inherited in an autosomal dominant manner and is caused by mutations in the FLNB gene. Management may include surgeries (especially for hip dislocation), and physiotherapy
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Pseudohypoparathyroidism type 1A

Retrieved: 27-07-2015
Source: GARD (Original article)

Pseudohypoparathyroidism type 1A

Pseudohypoparathyroidism type 1A is a genetic disorder that resembles hypoparathyroidism (lowered levels of parathyroid hormone), but is caused by a lack of response to parathyroid hormone rather than having too little of the hormone itself. This condition is very similar to hypoparathyroidism, with low calcium levels and high phosphate levels in the blood. This results in the characteristic symptoms which are generally first seen in childhood. There are two different types of pseudohypoparathyroidism. Type 1A is caused by a mutation in the GNAS gene and is inherited in an autosomal dominant manner. This defect also causes short stature, a round face, and short hand bones, which is referred to as Albright's hereditary osteodystrophy
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Pseudohypoparathyroidism type 1C

Retrieved: 27-07-2015
Source: GARD (Original article)
Associated genes: gnas

Pseudohypoparathyroidism type 1C

Pseudohypoparathyroidism type 1C is a genetic disorder that resembles hypoparathyroidism (lowered levels of parathyroid hormone), but is caused by a lack of response to parathyroid hormone rather than having too little of the hormone itself. This condition is very similar to hypoparathyroidism, with low calcium levels and high phosphate levels in the blood. This condition is also associated with short stature, a round face, and short hand bones, which is referred to as Albright's hereditary osteodystrophy. It is distinguished from pseudohypoparathyroidism type 1A because those with type 1C do not have a defect in activity of a particular protein. It is inherited in an autosomal dominant fashion and is caused by a specific mutation in the GNAS gene
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Pseudopseudohypoparathyroidism

Retrieved: 27-07-2015
Source: GARD (Original article)

Pseudopseudohypoparathyroidism

Pseudopseudohypoparathyroidism (PPHP) is an inherited condition characterized by the constellation of clinical features referred to as Albright hereditary osteodystrophy, which includes short stature, obesity, round face, and short hand bones. Some have intellectual disability. Affected individuals do not show resistance to parathyroid hormone (PTH) and thus do not have hypoparathyroidism. PHPP is caused by mutations in the GNAS gene and is inherited in an autosomal dominant fashion. This condition is usually inherited from the father (genomic imprinting). PPHP is genetically related to pseudohypoparathyroidism type Ia (PHP-1a) in that both share the same signs and symptoms, except that individuals with PPHP do not show resistance to PTH as seen in individuals with PHP-1a. Both PHP-1a and PPHP are caused by mutations that affect the function of the GNAS gene. But people who inherit the mutation from their mother develop PHP-1a; whereas those who inherit the mutation from their father develop PPHP
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Satoyoshi syndrome

Retrieved: 27-07-2015
Source: GARD (Original article)

Satoyoshi syndrome

Satoyoshi syndrome is a rare condition characterized by progressive, painful, intermittent muscle spasms, diarrhea or unusual malabsorption, amenorrhea, alopecia universalis, short stature, and skeletal abnormalities. Progressive painful intermittent muscle spasms usually start between 6 to 15 years of age. Alopecia universalis also appears around age 10. About half of affected individuals experience malabsorption, specifically of carbohydrates. The skeletal abnormalities may be secondary to muscle spasms. The main endocrine disorder is primary amenorrhea. All cases have apparently been sporadic, even when occurring in large families. The exact cause is unknown; but some researchers have speculated that Satoyoshi syndrome is an autoimmune disorder

Retrieved: 27-07-2015
Source: OMIM (original)
Associated genes: b3galt6

Description

A number sign (#) is used with this entry because Ehlers-Danlos syndrome progeroid type 2 (EDSP2) is caused by compound heterozygous mutation in the B3GALT6 gene (615291) on chromosome 1p36.

Mutation in the B3GALT6 gene can also cause spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMDJL1; 271640), which has overlapping features with EDSP.The features of the progeroid form of Ehlers-Danlos syndrome include an aged appearance, developmental delay, short stature, craniofacial disproportion, generalized osteopenia, defective wound healing, hypermobile joints, hypotonic muscles, and loose but elastic skin (Okajima et al., 1999).

For a discussion of genetic heterogeneity of EDSP, see EDSP1 (130070).

Molecular genetics

In 4 patients from 3 families with a progeroid form of EDS who did not have mutations in the B4GALT7 gene, Nakajima et al. (2013) performed Sanger sequencing of the B3GALT6 gene and found that all 4 patients were compound heterozygous for a frameshift and a missense mutation (615291.0007-615291.0011). Nakajima et al. (2013) showed that the GalT-II activities of a missense mutation that was common to 2 of the families (S309T; 615291.0008) were significantly decreased compared to wildtype, suggesting loss of function. The mutations were not detected in more than 200 ethnically matched controls or in public databases, including the 1000 Genomes Database.

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Weight]; Low weight

HEAD AND NECK: [Face]; Prominent forehead; Flat face; [Eyes]; Prominent eyes; Proptosis; Blue sclerae; [Mouth]; Long upper lip; Cleft palate (rare)

CHEST: [Ribs, sternum, clavicles, and scapulae]; Pectus excavatum (rare)

SKELETAL: Large joint laxity; [Spine]; Platyspondyly; Kyphoscoliosis; Anterior beak of vertebral body; [Pelvis]; Short ilia; Hip dislocation; Prominent lesser trochanter; [Limbs]; Restricted elbow movement; Elbow malalignment; Metaphyseal flaring; Epiphyseal dysplasia of femoral head; [Hands]; Spatulate finger; Finger laxity; Hand contracture (rare); Advanced carpal ossification; Carpal fusion (rare); Metacarpal shortening; [Feet]; Clubfeet

SKIN, NAILS, HAIR: [Skin]; Doughy skin; Hyperextensible skin; Cutis laxa; [Hair]; Sparse hair

NEUROLOGIC: [Central nervous system]; Hypotonia; Developmental delay (rare)

MOLECULAR BASIS: Caused by mutation in the UDP-Gal:beta-Gal beta-1,3-galactosyltransferase polypeptide 6 gene (B3GALT6, 615291.0007)


Retrieved: 27-07-2015
Source: OMIM (original)
Associated genes: b3galt6, kif22

Description

A number sign (#) is used with this entry because spondyloepimetaphyseal dysplasia with joint laxity type 1 with or without fractures (SEMDJL1) is caused by homozygous or compound heterozygous mutation in the B3GALT6 gene (615291) on chromosome 1p36.

Mutation in the B3GALT6 gene can also cause a progeroid type of Ehlers-Danlos syndrome (EDSP2; 615349), which has overlapping features with SEMDJL1.Spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMDJL1) is characterized by vertebral abnormalities and ligamentous laxity that result in spinal misalignment and progressive severe kyphoscoliosis, thoracic asymmetry, and respiratory compromise resulting in early death. Nonaxial skeletal involvement includes elbow deformities with radial head dislocation, dislocated hips, clubfeet, and tapered fingers with spatulate distal phalanges. Many affected children have an oval face, flat midface, prominent eyes with blue sclerae, and a long philtrum. Palatal abnorma...

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Dwarfism; [Weight]; Low weight

HEAD AND NECK: [Face]; Oval face; Flat midface; Prominent forehead; Micrognathia; [Eyes]; Prominent eyes; Blue sclera; Myopia; Congenital myopia; Lens dislocation; Proptosis; [Mouth]; Cleft palate (31% of patients); High-arched palate (12% of patients); Long philtrum; Long upper lip; [Neck]; Short neck

CARDIOVASCULAR: [Heart]; Atrial septal defect; Ventricular septal defect; Mitral insufficiency; Bicuspid aortic valve

CHEST: [External features]; Thoracic asymmetry; [Ribs, sternum, clavicles, and scapulae]; Anterior flaring of ribs; Cupped ribs; 11 pairs of ribs

SKELETAL: Joint laxity; Joint dislocation; Spondyloepimetaphyseal dysplasia; Joint contractures; Osteoporosis; Spontaneous fractures; [Spine]; Progressive kyphoscoliosis; Ovoid vertebrae (infancy); Platyspondyly (childhood); Irregular endplates (childhood); Gross spinal malalignment; Anterior beak of vertebral body; Scoliosis; [Pelvis]; Large, flared iliac wings; Hypoplastic iliac body; Narrow pubic bones; Delayed ossification of femoral capital epiphyses; Hip dislocation; Hip subluxation; Short femoral necks; Coxa valga; Prominent lesser trochanter; [Limbs]; Genu valga (80% of patients); Radial head dislocation; Radial head subluxation; Radial bowing; Restricted elbow movement; Elbow malalignment; Short, slender long bones; Wide metaphyses; Metaphyseal flaring; Epiphyseal dysplasia of femoral head; Abnormal trabecular pattern; [Hands]; Hypermobile digits; Spatulate terminal phalanges (especially thumbs); Short metacarpals; Hand contracture (rare); Advanced carpal ossification; Carpal fusion (rare); [Feet]; Talipes equinovarus; Pes planus; H...


Retrieved: 27-07-2015
Source: OMIM (original)
Associated genes: col2a1

Clinical features

A number sign (#) is used with this entry because spondyloperipheral dysplasia is caused by heterozygous mutation in the alpha-1 type II collagen gene (COL2A1; 120140) on chromosome 12q13.Kelly et al. (1977) described a father and 2 children (son and daughter) with an identical skeletal dysplasia of unusual type. It fell generally in the category of spondyloepiphyseal dysplasias. Platyspondyly and severe hip changes were present. The hands and feet were very short as in peripheral dysostosis. The ulna was very short distally, so that it showed deficiency at the wrist. Some of the metatarsals were particularly short. The father was 144 cm tall; the 31-year-old daughter was 142 cm tall; and the 30-year-old son was 154 cm tall. The pedigree was equally consistent with autosomal dominant or autosomal recessive inheritance because the affected father was married to his first cousin and came himself from a consanguineous mating. The families reported by Sybert et al. (1979) and by Vanek (1983) have some similarities; in these families, inheritance seems to have been autosomal dominant. The single case reported by Goldblatt and Behari (1987) also has some similarities. The patient was 108 cm tall at the age of 20, with an arm span of 125.5 cm; the forearms showed mild bilateral bowing. The shortening of the bones of the hands and feet was possibly more striking in the patients reported by Kelly et al. (1977).

Sorge et al. (1995) described the disorder in a mother and 3 of her children, 2 daughters and a son. In addition to platyspondyly with endplate indentations and brachydactyly, the proband had a characteristic, 'pugilistic' face, sensorineural deafness, and mental retardation.

Zankl et al. (2004) reported 2 patients with findings similar to those described by Zabel et al. (1996): clubfeet, midface hypoplasia, early-onset high grade myopia, platyspondyly, epiphyseal dysplasia,...

Symptoms

INHERITANCE: Autosomal dominant

GROWTH: [Height]; Short stature

HEAD AND NECK: [Face]; 'Pugilistic facies'; Midface hypoplasia; [Ears]; Hearing loss, sensorineural

CHEST: [External features]; Pectus carinatum; Barrel-shaped chest

SKELETAL: Spondyloepiphyseal dysplasia; [Spine]; Platyspondyly, mild; Biconcave disc (fish-mouth vertebrae); Kyphosis; [Pelvis]; Short ilia; Horizontal acetabulae; Flattened capital femoral epiphyses; Acetabular spurs (infancy); [Limbs]; Short ulna; Absent styloid processes; Limited elbow extension; [Hands]; Short fingers; Broad hands; Very short distal phalanges (2nd, 3rd, 4th, 5th); Short metacarpals (2nd, 3rd, 4th, 5th); Cone-shaped epiphyses; Short, broad thumbs; Brachydactyly E-like changes; Short proximal and middle phalanges; [Feet]; Short feet; Short phalanges; Short metatarsals (4th)

MOLECULAR BASIS: Caused by mutation in the collagen II, alpha-1 polypeptide gene (COL2A1, 120140.0030)


Retrieved: 27-07-2015
Source: OMIM (original)

Clinical features

Ruvalcaba et al. (1971) described 2 brothers, born to unrelated parents, who showed mental retardation, short stature, microcephaly, peculiar facies with hooked nose and small mouth, narrow thoracic cage with pectus carinatum, hypoplastic genitalia, hypoplastic 'onion skin' cutaneous lesions, and skeletal deformities including short metatarsals and metacarpals and epiphysitis of the spine. Because 2 female maternal cousins showed some of the same features, X-linked semi-dominant inheritance was considered. One of the girls seems to have been fully affected, however. She died at age 17 years with congenital hydrocephalus and the Dandy-Walker anomaly.

Geormaneanu et al. (1978) reported a 7-year-old boy and his father with the syndrome and a possibly coincidental t(13q;14q) translocation.

Bianchi et al. (1984) described a single case in an Italian male.

Under the designation of Ruvalcaba syndrome, Sugio and Kajii (1984) described a kindred with 9 affected persons in 4 generations. They showed postnatal growth retardation, oval face with high forehead, antimongoloid slant of palpebral fissures (the kindred was Japanese), small, beaked nose with hypoplastic nasal alae, small downturned mouth with thin vermilion borders, pointed chin, and short digits. This kindred differed from that reported by Ruvalcaba et al. (1971) in the lack of mental retardation. Hunter (1985) disagreed with the diagnosis of Sugio and Kajii (1984) and considered the disorder to be different from Ruvalcaba syndrome. He pointed to the absence of mental retardation and microcephaly and the presence of sparse hair, beaked nose, long upper lip, and severe degree of metacarpal phalangeal shortness. Niikawa and Kamei (1986) proposed that this is a separate entity which should be called trichorhinophalangeal syndrome, type III (TRPS3; 190351).

Adachi et al. (2010) reported a Japanese girl with clinical manifestations identical to those reported by Ruvalcaba et al. (1971). Born of unrelated parents, she presented at age 6 months with failure to thrive, multiple congenital anomalies, and developmental delay. She had microce...

Symptoms

INHERITANCE: Autosomal dominant

GROWTH: [Height]; Short stature

HEAD AND NECK: [Head]; Microcephaly; [Eyes]; Downslanting palpebral fissures; Central tapetoretinal dystrophy; [Nose]; Narrow nose; Hypoplastic alae nasi; [Teeth]; Crowded teeth

CHEST: [External features]; Narrow chest; [Breasts]; Large areolae

GENITOURINARY: [External genitalia, male]; Inguinal hernia; [Internal genitalia, male]; Cryptorchidism

SKELETAL: [Spine]; Scoliosis; Kyphosis; [Limbs]; Short limbs; Limitation of elbow extension; Prominent elbows; [Hands]; Small hands; Short metacarpals; Short phalanges; [Feet]; Small feet; Short metatarsals

NEUROLOGIC: [Central nervous system]; Mental retardation

ENDOCRINE FEATURES: Delayed puberty


Retrieved: 27-07-2015
Source: Orphanet (original)
Associated genes: cant1, chst3

Desbuquois syndrome (DBQD) is an osteochondrodysplasia characterized by severe micromelic dwarfism, facial dysmorphism, joint laxity with multiple dislocations, vertebral and metaphyseal abnormalities and advanced carpotarsal ossification. Two forms have been distinguished on the basis of the presence (type 1) or the absence (type 2) of characteristic hand anomalies. A variant form of DBQD, Kim variant (see these terms), has also been described and is characterized by short stature and articular, minor facial and significant hand anomalies. To date, less than 50 cases have been described in the literature. DBQD is characterized by severe micromelic dwarfism, facial dysmorphism (round flat face, prominent eyes, midface hypoplasia, short nose, microstomia, long upper lip with flat philtrum, microretrognathia, often resulting in isolated Pierre Robin syndrome (see this term)), thoracic hypoplasia, kyphoscoliosis, severe joint laxity with dislocation, and osteopenia. Additional features include glaucoma, cardiac septal defects, lung hypoplasia, obesity and clubbed feet with rocker bottom appearance. Two forms have been distinguished on the basis of the presence (type 1) or the absence (type 2) of characteristic hand anomalies (accessory ossification center distal to the second metacarpal, bifid distal phalanx, or thumb with delta-shaped phalanx). A variant form of DBQD, Kim variant, has been described in 7 patients originating from Korea and Japan, and is characterized by short stature, articular and minor facial anomalies, together with significant hand anomalies including short metacarpals and elongated phalanges with advanced carpal bone age. DBQD type 1 and Kim variant are caused by mutation in the gene CANT1 (17q25.3). However, the function of CANT1 is still unknown. Mutations in the gene XYLT1 (16p12) has been reported to cause DBQD type 2. XYLT1 encodes xylosyltransferase 1 which is involved in proteoglycan synthesis. However not all DBQD type 2 have XYL...


Retrieved: 27-07-2015
Source: OMIM (original)
Associated genes: trps1

Clinical features

A number sign (#) is used with this entry because of evidence that type III TRPS is caused by mutation in the TRPS1 gene (604386), which is also the site of mutation in type I TRPS (190350).Sugio and Kajii (1984) described a kindred in which 9 persons in 4 generations showed a syndrome of sparse hair, beaked nose, long upper lip, and severe metacarpophalangeal shortening. They reported the condition as an example of Ruvalcaba syndrome (180870); however, as pointed out by Hunter (1985), the disorder could be differentiated from Ruvalcaba syndrome by the absence of mental retardation and microcephaly and the presence of other changes resembling those of trichorhinophalangeal syndrome I (190350). The abnormalities of the hands and feet present in the patients of Sugio and Kajii (1984) were more severe, however, than those of TRPS1 patients. Niikawa and Kamei (1986) reported on a sporadic case who had similar manifestations and proposed that the condition should be recognized as a new syndrome known as TRPS type III, or Sugio-Kajii syndrome. Nagai et al. (1994) added another family in which 4 persons in 3 generations were affected with 1 instance of male-to-male transmission. The sparse hair, 'pear-shaped nose' clearly demonstrated in the figures, and cone-shaped epiphyses were features like those of TRPS types I and II (TRPS2; 190350), but the presence of severe generalized shortening of all phalanges and metacarpals differentiated the condition from TRPS1 and the absence of mental deficiency and exostoses from TRPS2.

Vilain et al. (1999) reported a case of TRPS III in a patient of European descent. The patient had typical features ...

Symptoms

INHERITANCE: Autosomal dominant

GROWTH: [Height]; Short stature; Normal birth length; [Weight]; Normal birth weight

HEAD AND NECK: [Face]; Long, flat philtrum; [Ears]; Protruding ears; [Eyes]; Laterally sparse eyebrows; [Nose]; Pear-shaped nose; Hypoplastic alae nasi; [Mouth]; Thin upper lip; [Teeth]; Crowded teeth; Supernumerary teeth

SKELETAL: Mild osteopenia; Delayed bone age before puberty; Accelerated bone age after puberty; [Spine]; Scoliosis; [Pelvis]; Coxa plana; Coxa magna; [Limbs]; Absence of exostoses; [Hands]; Short hands; Cone-shaped epiphyses (middle phalanges); Severe brachydactyly; Short metacarpals; Short phalanges; [Feet]; Short feet; Short metatarsals

SKIN, NAILS, HAIR: [Hair]; Sparse hair; Laterally sparse eyebrow

NEUROLOGIC: [Central nervous system]; Normal intelligence

MISCELLANEOUS: Cone-shaped epiphyses usually not present before age 2 years; Allelic to TRP1 (190350); TRP2 (Langer-Giedion syndrome, 150230) is a microdeletion syndrome involving deletions of both the TRPS1 (604386) and EXT1 (608177) genes

MOLECULAR BASIS: Caused by mutations in the zinc finger transcription factor TRPS1 gene (TRPS1, 604386.0007)


Retrieved: 27-07-2015
Source: OMIM (original)

Description

Phillips et al. (1981) described a brother and sister, children of normal parents, who had retinitis pigmentosa (leading to near blindness) and metaphyseal chondrodysplasia (with particularly marked shortening of the metacarpals and terminal phalanges).

Symptoms

Eyes: Retinitis pigmentosa

Skel: Metaphyseal dysplasia; Short metacarpals; Short terminal phalanges

Inheritance: Autosomal recessive


Retrieved: 27-07-2015
Source: OMIM (original)
Associated genes: slc39a13

Clinical features

A number sign (#) is used with this entry because the spondylocheirodysplastic form of Ehlers-Danlos syndrome (SCD-EDS) is caused by homozygous mutation in the zinc transporter gene SLC39A13 (608735) on chromosome 11p11.2.Giunta et al. (2008) described a 'spondylocheiro dysplastic form of Ehlers-Danlos syndrome' in 6 patients from 2 consanguineous families. Clinical features included postnatal growth retardation, moderate short stature, protuberant eyes with bluish sclerae, hands with finely wrinkled palms, atrophy of the thenar muscles, and tapering fingers. Patients had thin, hyperelastic skin and hypermobile small joints consistent with an Ehlers-Danlos-like phenotype. Radiologic features included mild to moderate platyspondyly, mild to moderate osteopenia of the spine, small ileum, flat proximal femoral epiphyses, short, wide femoral necks, and broad metaphyses (elbows, knees, wrists, and interphalangeal joints).

Biochemical features

Giunta et al. (2008) found that all 6 patients with SCD-EDS had an increased lysyl pyridinoline/hydroxylysyl pyridinoline (LP/HP) ratio indicating underhydroxylation of collagen. The ratio in patients (mean 0.89 +/- 0.18) was lower than that in individuals with EDS VI (225400; mean 5.97 +/- 0.99) but markedly higher than that in contr...

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Short stature, moderate; [Weight]; Birthweight at or below 3rd centile; [Other]; Growth retardation, postnatal

HEAD AND NECK: [Eyes]; Protuberant eyes; Blue sclerae; Downslanting palpebral fissures; Corneal diameter, normal; [Mouth]; High palate; Bifid uvula; [Teeth]; Delayed eruption of teeth; Malocclusion; Hypodontia

SKELETAL: [Spine]; Platyspondyly; Osteopenia; Irregular endplates; [Pelvis]; Small ilia; Short, wide femoral neck; Mildly flattened proximal femoral epiphyses; [Limbs]; Joint laxity (elbow); Widened metaphyses (elbows and knees); [Hands]; Small joint laxity; Finger contractures; Slender, tapered fingers; Finely wrinkled palms; Thenar muscle atrophy; Hypothenar muscle atrophy; Inability to adduct thumbs; Short metacarpals; Short phalanges; Widened metaphyses (metacarpal and phalanges); Flattened epiphyses (metacarpal and phalanges); [Feet]; Pes planus

SKIN, NAILS, HAIR: [Skin]; Velvety, smooth skin; Hyperelastic skin; Thin skin; Easy bruisability; Finely wrinkled palms; Prominent veins; Cigarette-paper scars; Delayed wound healing

MUSCLE, SOFT TISSUE: Thenar muscle atrophy; Hypothenar muscle atrophy

LABORATORY ABNORMALITIES: Lysyl pyridinoline/hydroxylysyl pyridinoline (LP/HP) ratio approximately 1; Normal lysyl hydroxylase activity; Normal prolyl 4-hydroxylase activity

MISCELLANEOUS: Waddling gait

MOLECULAR BASIS: Caused by mutation in the solute carrier family 39 (zinc transporter), member 13 gene (SLC39A13, 608735.0001)


Retrieved: 27-07-2015
Source: OMIM (original)

Description

In a kindred in which multiple members had somewhat short stature, round facies, and brachydactyly type E (113300), Czeizel and Goblyos (1989) described also the appearance of the secundum type of atrial septal defect (ASD II). The shortening of the metacarpals was most pronounced in the 4th metacarpal, but not limited to that bone.

Symptoms

Growth: Short stature

Facies: Round facies

Limbs: Brachydactyly; Short metacarpals, esp. 4th; Variable short metatarsals

Cardiac: Atrial septal defect (ASD II)

Inheritance: Autosomal dominant


Retrieved: 27-07-2015
Source: Orphanet (original)

Beemer-Ertbruggen syndrome is a lethal malformation syndrome reported in 2 brothers of first-cousin parents that is characterized by hydrocephalus, cardiac malformation, dense bones, and unusual facies with down-slanting palpebral fissures, bulbous nose, broad nasal bridge, micrognathia and a long upper lip. Transmission is likely autosomal recessive. There have been no further descriptions in the literature since 1984. Last update: January 2014


Retrieved: 27-07-2015
Source: OMIM (original)

Description

Christian et al. (1972) described short thumbs and first toes with abduction of these digits. The shortening involves the metacarpals, metatarsals, and distal phalanges, while the proximal and middle phalanges are of normal length. Although no male-to-male transmission was observed, males and females were affected to a similar degree. Four successive generations and 6 sibships were affected. All 8 affected members were mentally retarded. Sharma et al. (1994) described a father and daughter with the same form of brachydactyly but without mental retardation. The changes in the hands and feet were much like those reported by Mononen et al. (1992) (see 301940), but Sharma et al. (1994) considered that to be a different entity because it showed missing phalanges, short stature, and epiphyseal and metaphyseal changes indicative of a skeletal dysplasia.

Symptoms

Limbs: Short abducted thumbs; Short abducted first toes; Short distal phalanges; Short metacarpals; Short metatarsals; Normal proximal and middle phalanges

Inheritance: Autosomal dominant


Retrieved: 27-07-2015
Source: OMIM (original)

Description

Pearlman et al. (1964) described mother and daughter with multiple carpal and tarsal synostoses (carpal and tarsal coalition) as well as radial-head subluxation, aplasia or hypoplasia of the middle phalanges, and metacarpophalangeal synostoses. The latter synostoses seem comparable to those that occur in the 2 more distal joints in the 2 forms of symphalangism (185700, 185800). Although the authors felt this to be the disorder described by Nievergelt (see Nievergelt syndrome, 163400), this is almost certainly not the case but a distinct entity is involved. Bersani and Samilson (1957) described a mother and her daughter and son with massive synostosis of tarsal bones. No specific statement was made about the state of the carpal bones. Wray and Herndon (1963) observed calcaneonavicular coalition in 3 generations. Isolated fusion of carpal and tarsal bones was described by Kewesch (1934). Diamond (1974) observed talocalcaneal coalition in a mother and 3 of her 8 children. It is probable that this is a disorder distinct from the more common calcaneonavicular bridges.

Symptoms

Limbs: Carpal synostosis; Tarsal synostosis; Digital synostosis; Radial-head subluxation; Aplasia/hypoplasia of middle phalanges; Metacarpophalangeal synostoses; Absent phalanges; Short metacarpals

Nails: Absent nails

Nose: Hypoplastic alae nasae

Inheritance: Autosomal dominant


Retrieved: 27-07-2015
Source: OMIM (original)

Clinical features

Arias et al. (1976) described a seemingly new form of skeletal dysplasia among the Irapa Indians of Venezuela. Features included short spine from platyspondyly, short metacarpals and metatarsals, and striking changes in the proximal femoral and distal humeral epiphyses.

Hernandez et al. (1980) described SEMDIT in 3 sibs from a Mexican mestizo family. Arias (1981) suggested SEMI as a simple designation.

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Short stature, disproportionate short-trunked (identifiable at birth)

CHEST: [Ribs, sternum, clavicles, and scapulae]; Widened costochondral junction; Pectus carinatum

SKELETAL: Osteoarthritis; Spondyloepimetaphyseal dysplasia; [Spine]; Platyspondyly; Small sacrum; Increased lumbar lordosis; [Pelvis]; Protruding iliac wings; Coxa vara; Wide femoral neck; [Limbs]; Short arms; Limited forearm extension; Metaphyseal dysplasia; Severe epiphyseal hypoplasia; Osteoarthritis; Arthralgias; Diaphyseal shortness; Genu valgum; [Hands]; Short metacarpals; Short, broad hands; Capitate-hamate fusion; [Feet]; Short metatarsals; Flat, broad feet; Long second toes

MISCELLANEOUS: Waddling gait


Retrieved: 27-07-2015
Source: OMIM (original)

Description

Nivelon et al. (1992) described 2 sibs with an apparently 'new' chondrodysplasia-pseudohermaphroditism syndrome. Both had severe dwarfism, antenatal in origin, with general chondrodysplasia, severe microcephaly with cerebellar vermis hypoplasia, hypoplastic iris, and coloboma of the optic disc. The first affected sib had shown intrauterine growth retardation on ultrasonography at the age of 5 months, at which time the limbs were considered to be short. The karyotype at that time was 46,XY; however, a phenotypic female was delivered at 38 weeks of gestation. The external genitalia and the internal genitalia, examined by sonography and laparotomy at the age of 14 months, were considered normal. The SRY gene, studied in 2 laboratories, was found to be normal with no deletion. The child was 3 years old at last description. The second affected pregnancy began when the first child was 2.5 years old. The karyotype was normal 46,XX. At 17 weeks of gestation, ultrasound examination showed abnormalities in the vertebral column and thereafter there were other skeletal changes prompting termination of the pregnancy. Both sibs showed narrow, bell-shaped thorax, micromelia, trapezoidal shape of vertebral bodies, abnormal clavicles, and short metacarpals and phalanges. The parents were young and nonconsanguineous.

Symptoms

Growth: Severe antenatal dwarfism

GU: Male pseudohermaphroditism

Skel: Chondrodysplasia

Head: Microcephaly

Neuro: Cerebellar vermis hypoplasia

Eyes: Iris hypoplasia; Optic disc coloboma

Thorax: Narrow, bell-shaped thorax

Limbs: Micromelia; Short metacarpals and phalanges

Radiology: Trapezoidal shaped vertebral bodies; Abnormal clavicles

Lab: 46,XY karyotype

Inheritance: ? Autosomal recessive


Retrieved: 27-07-2015
Source: Orphanet (original)
Associated genes: rmrp

This disease has been moved to Cartilage-hair hypoplasia


Retrieved: 27-07-2015
Source: WIKIPEDIA (original)
Osteochondromatosis is a condition involving a proliferation of osteochondromas. Types include: Hereditary multiple exostoses Synovial osteochondromatosis


Retrieved: 27-07-2015
Source: Orphanet (original)
Associated genes: col11a1, slc35d1

Fibrochondrogenesis is a rare, neonatally lethal, rhizomelic chondrodysplasia. Eleven cases have been reported. The face is distinctive and characterized by protuberant eyes, flat midface, flat small nose with anteverted nares and a small mouth with long upper lip. Cleft palate, micrognathia and bifid tongue can occur. The limbs show marked shortness of all segments with relatively normal hands and feet. No internal anomalies other than omphalocele have been reported. Transmission is probably autosomal recessive. Recurrence in a consanguineous family (affecting both sexes) and concordance of affected male twins have been reported. Expert reviewer(s) Pr Lihadh AL-GAZALI Last update: February 2005


Retrieved: 27-07-2015
Source: OMIM (original)

Description

Bork et al. (1987) reported a new type of ectodermal dysplasia with congenital hypotrichosis and uncombable hair, associated with juvenile cataracts, retinal pigmentary dystrophy, oligodontia, and brachymetacarpy. The condition was inherited as an autosomal dominant. Silengo et al. (1993) reported an isolated case. They illustrated the presence of supernumerary inferior lateral incisors and microdontia. The patient was mildly retarded. Scanning electron microscopy showed the presence of longitudinal grooves giving the typical appearance of pili canaliculi. Uncombable hair occurs as an isolated trait inherited as an autosomal dominant (191480). The uncombable hair is also referred to as 'spun-glass' hair.

Symptoms

INHERITANCE: Autosomal dominant

HEAD AND NECK: [Eyes]; Retinal pigmentary dystrophy; Juvenile cataract; [Teeth]; Oligodontia; Microdontia; Supernumerary teeth

GENITOURINARY: [External genitalia, male]; Hypospadias

SKELETAL: [Hands]; Brachydactyly; Short proximal phalanges; Short metacarpals; [Feet]; Brachydactyly

SKIN, NAILS, HAIR: [Hair]; Uncombable hair; Pili canaliculi; Pili trianguli


Retrieved: 27-07-2015
Source: OMIM (original)

Description

Tuomaala and Haapanen (1968) described a Finnish family in which 2 sisters and a brother had an identical syndrome of congenital anodontia, small maxilla giving an impression of mandibular prognathism, short stature with particular shortening of the metacarpals and metatarsals, little hair growth, albinoidism, and multiple ocular abnormalities including strabismus, nystagmus, distichiasis, lenticular opacities, and high-grade myopia. The parents were not known to be related but came from the same parish in northeast Finland.

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Short stature

HEAD AND NECK: [Ears]; Low-set ears; [Eyes]; Downslanting palpebral fissures; Strabismus; Thin eyelashes; Distichiasis; Myopia; Irregular nystagmus; Cataract; Corneal opacities; Tarsal hypoplasia; [Teeth]; Anodontia

CHEST: [Breasts]; Small breast; Hypoplastic nipples; Unpigmented areola

GENITOURINARY: [External genitalia, female]; Hypoplastic labia

SKELETAL: [Skull]; Hypoplastic maxilla; [Hands]; Short fingers; Short metacarpals (3rd-5th); [Feet]; Short toes (2nd-5th); Short metatarsals

SKIN, NAILS, HAIR: [Skin]; Albinoidism; [Hair]; Thin hair; Absent pubic hair; Absent axillary hair; Thin eyelashes


Retrieved: 27-07-2015
Source: OMIM (original)

Clinical features

A number sign (#) is used with this entry because of evidence that a skeletal malformation with features overlapping those of brachydactyly types E and D (BDD; 113200) is caused by heterozygous mutation in the HOXD13 gene (142989) on chromosome 2q31.

Another form of brachydactyly type E, BDE2 (613382), is caused by heterozygous mutation in the PTHLH gene (168470) on chromosome 12p12.1-p11.2.

Also see the hypertension and brachydactyly syndrome (112410).In type E brachydactyly, shortening of the fingers is mainly in the metacarpals and metatarsals. Wide variability in the number of digits affected occurs from person to person, even in the same family. Male-to-male transmission of type E brachydactyly has been observed (McKusick and Milch, 1964).

Hertzog (1968) suggested that there are at least 3 subtypes of BDE: E1, in which shortening is limited to fourth metacarpals and/or metatarsals (Hortling et al., 1960); E2, in which variable combinations of metacarpals are involved, with shortening also of the first and third distal and the second and fifth middle phalanges (McKusick and Milch, 1964); and E3, a dubious category which may have a variable combination of short metacarpals without phalangeal involvement.

Some individuals with BDE are moderately short of stature and have round facies but do not have ectopic calcification (or ossification), mental retardation or cataract as in pseudohypoparathyroidism (103580) which is otherwise a clinically similar entity. This phenotype occurs with a chromosomal aberration, the XO Turner syndrome. Also see brachydactyly-nystagmus-cerebellar ataxia (Biemond syndrome I), a probable dominant trait. Poznanski et al. (1977) concluded that 'brachydactyly E is indistinguishable radiologically from the PHP-PPHP syndrome'.

Newcombe and Keats (1969) described an extensively affected kindred with a dominant pedigree pattern (their pedigree II) as having peripheral dysostosis. The description resembled that in the family of McKusick and Milch (1964) except for cone epiphyses. The authors thought that the presence of cone epiphyses in their family was a distinguishing feature.

In a family reported by Gorlin and Sedano (1971), type E brachydactyly was associated with multiple impacted teeth. Gorlin and Sedano (1971) gave the designation 'cryptodontic metacarpalia' to type E brachydactyly associated with multiple impacted teeth. The clavicles were unusually straight and short. Whether this is a distinct entity is not clear.

Cytogenetics

Wilson et al. (1995) found a cytogenetically visible de novo deletion of 2q37 in 4 patients in whom brachydactyly type E was combined with mental retardation to ...

Symptoms

Growth: Moderately short stature

Limbs: Brachydactyly; Short metacarpals; Variable short metatarsals

Facies: Round facies

Teeth: Multiple impacted teeth

Skel: Straight and short clavicles

Radiology: Radiologically indistinguishable from the PHP-PPHP syndrome

Inheritance: Autosomal dominant