We found 38 diseases and 32 genes matching your search

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Bruck syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: fkbp10, plod2, col1a1

Bruck syndrome is characterised by the association of osteogenesis imperfecta and congenital joint contractures. Prevalence is unknown but less than 40 cases have been reported in the literature so far. Features include osteoporosis and bone fragility, progressive joint contractures sometimes associated with pterygia, wormian bones, scoliosis due to vertebral deformities and short stature. Mental development is normal. The syndrome is genetically heterogeneous: the locus was mapped to chromosome 17p12 in one family (Bruck syndrome 1) but mutations in the PLOD2 gene (3q24) encoding telopeptide lysyl hydroxylase (Bruck syndrome 2) have been identified in other affected individuals. Transmission is autosomal recessive. Last update: July 2008
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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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Frontal fibrosing alopecia

Retrieved: 27-07-2015
Source: GARD (Original article)
Associated genes: pparg, htn1, tnfsf13b, apol2

Frontal fibrosing alopecia

Frontal fibrosing alopecia (FFA) is a form of lichen planus follicularis that is characterized primarily by slowly progressive hair loss (alopecia) and scarring on the scalp near the forehead. In some cases, the eyebrows, eye lashes and/or other parts of the body may be involved, as well. Although it has been suggested that FFA may be due to hormonal changes or an autoimmune response, the exact cause of this condition is not yet known. There is currently no cure for FFA; however, treatment with certain types of medications may stop or slow hair loss in some cases
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Lichen planopilaris

Retrieved: 27-07-2015
Source: GARD (Original article)
Associated genes: pparg, htn1, tnfsf13b, apol2

Lichen planopilaris

Lichen planopilaris is a form of lichen planus that mainly affects the scalp and primarily affects middle-aged adults. It usually causes tiny red papules to appear around a cluster of hairs. Rarely, blistering occurs in the lesions. The hair follicles on the scalp are mainly affected in this form, although lesions may also be found on the skin and mucous membranes. Follicular lichen planus is the most common form of lichen planus found in the scalp. Commonly encountered symptoms and signs are increased hair shedding, itching, scaling, burning, and tenderness. Hair loss occurs and may be permanent if the disease is sufficiently active to cause permanent scarring, a condition called cicatricial alopecia. Treatment is usually with steroids
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Graham-Little syndrome

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Associated genes: pparg, htn1, tnfsf13b, apol2
Graham-Little syndrome is a cutaneous condition characterized by lichen planus-like skin lesions.Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.

See also

List of cutaneous conditions
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Rare lichen planus

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: pparg, htn1, tnfsf13b, apol2

Lichen planus (LP) is a common inflammatory dermatosis characterized by the development of pruritic violaceous papules or plaques on mucocutaneous surfaces. Eruptions can involve the face, neck, limbs, back, genitalia, tongue, buccal mucosa, nails, and scalp. LP comprises rare variants affecting the skin and the mucosa. Rare cutaneous LP includes linear LP (referring to blaschkoid and zosteriform distributions of lichenoid lesions), actinic LP, annular LP, atrophic LP, annular atrophic LP, lichen planopilaris (comprising Graham Little-Piccardi-Lassueur syndrome and frontal fibrosing alopecia), lichen planus pigmentosus, and lichen planus pemphigoides (see these terms). Rare mucosal LP includes vulvovaginal gingival syndrome and LP sialadenitis (see these terms). Expert reviewer(s) Dr Stephanie ARNOLD Dr Susan COOPER Last update: May 2011
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Graham Little-Piccardi-Lassueur syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: pparg, htn1, tnfsf13b, apol2

Graham Little-Piccardi-Lassueur syndrome is a variant of lichen planopilaris (see this term) characterized by the clinical triad of progressive cicatricial (scarring) alopecia of the scalp, follicular keratotic papules on glabrous skin, and variable alopecia of the axillae and groin. It is a very rare disease but the exact prevalence is not known. It mainly affects women during adulthood (30-60 years of age). Scarring alopecia presents as small confluent patches that are atrophic and cicatricial in the center but erythematous and squamous around the edges. Follicular keratosis presents as pruritic, red-brown, follicular spiny papules on the trunk and extremities. Generally, the three clinical features appear simultaneously but in some cases, scalp alopecia precedes the follicular keratosis. Etiology is unknown. Expert reviewer(s) Dr Stephanie ARNOLD Dr Susan COOPER Last update: May 2011
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Lichen planopilaris

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: pparg, htn1, tnfsf13b, apol2

Lichen planopilaris (LPP) is a rare cutaneous variant of lichen planus (see this term) which affects hair follicles. It may occur on its own or in association with more common forms of lichen planus, usually classical type and/or oral lichen planus. The prevalence is unknown. LPP is more frequent in women than in men. The disease manifests in adulthood (40-60 years of age), with some rare cases in childhood. Patients present with peri-follicular inflammation and hair loss. They may be asymptomatic or have itch or discomfort. The scalp is the commonest area affected but any hair bearing skin may be affected, like for example the axillae or the pubic area. Perifollicular erythema, scales, and/or keratotic plugs are seen at the edge of the affected area. Single or multiple lesions of scarring alopecia lacking follicular orifices are typical. Two other variants of LPP can be observed: frontal fibrosing alopecia (FFA), and Lassueur-Graham-Little syndrome (see these terms). In FFA, there is symmetrical, progressive anterior hairline loss of the scalp associated with eyebrow loss. The Lassueur-Graham-Little syndrome constitutes a combination of lichen planus follicularis of the scalp with follicular keratosis and noncicatricial alopecia of the axillae and pubes. Etiology is unknown but LPP is thought to be an autoimmune disorder in which T-lymphocytes attack and destroy keratinocytes expressing unknown target antigens. Triggering factors could be pharmacologic agents, contact sensitizers or infectious agents. Diagnosis is based on clinical and histopathological findings. Biopsy of an inflammatory lesion shows a band-like perifollicular lymphocytic infiltrate at the level of the isthmus and infundibulum. There may be vacuolar changes of the basal layer and follicular plugging. In more advanced lesions, perifollicular fibrosis and replacement of hair follicles by fibrosis are found. Diagnosis is difficult in the later stages when inflammation disappears. Differentia...
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PHAVER syndrome

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

Phaver syndrome is a very rare syndrome characterized by the association of limb Pterygia, Heart anomalies, Autosomal recessive inheritance, Vertebral defects, Ear anomalies and Radial defects. It has been described in two sibs. One of the sibs also had a myelomeningocele. The reported cases suggest the condition is hereditary with probable autosomal recessive inheritance. Last update: October 2010
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Phaver syndrome

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

Description

Powell et al. (1993) described 2 sibs with vertebral, radial, congenital heart, and ear defects. The second born had limb pterygia and meningomyelocele. Some of the abnormalities in these 2 sibs occur in the VATER association; however, distinguishing these cases were pterygia, meningomyelocele, and probable autosomal recessive inheritance. Powell et al. (1993) proposed the acronym PHAVER syndrome for pterygia, heart defects, autosomal recessive inheritance, vertebral defects, ear anomalies, and radial defects. The sibs, a male and a female, were the offspring of young, healthy, nonconsanguineous parents. The girl had correction of aortic coarctation at the age of 2 months. The disorder in the male was diagnosed in utero and the pregnancy was interrupted.
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Second metatarsal-metacarpal syndrome

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

Clinical features

Christian et al. (1975) described a mother and daughter with a syndrome of metacarpal and metatarsal asymmetry, platyspondyly, carpal and tarsal fusions, syndactyly, articular dysplasia, and platyspondyly. The most striking finding was asymmetry in length of the second metacarpals and metatarsals. For example, the daughter had short left second metacarpal and short right second metatarsal, their counterparts on the other side being abnormally long.

Garcia-Cruz et al. (1995) reported a mother and daughter with a similar syndrome characterized by proximal and distal flexion contractures in the phalanges and by brachydactyly, clinodactyly, and ulnar and radial subdislocations of the fingers. Radiologically, the second metacarpal in the daughter was longer than the other metacarpals, with bone-carpal fusion and flexion contractures of the fingers of both hands. Thoracolumbar kyphoscoliosis and malformed vertebrae with dyssegmentation of L2-L3, cuneiform shape of T12 and L1, asymmetry of the pelvic bones, and exostotic lesions in the proximal third of the tibia and the distal third of the femur were also noted. The authors referred to the disorder as Christian spondylodigital syndrome.

Symptoms

Skel: Metacarpal and metatarsal asymmetry; Carpal and tarsal fusions; Platyspondyly

Inheritance: Autosomal recessive
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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)
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Platyspondyly with amelogenesis imperfecta

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

Clinical features

Verloes et al. (1996) described an apparently 'new' form of skeletal dysplasia with amelogenesis imperfecta and platyspondyly in a brother and sister born of consanguineous parents. Hallmarks were amelogenesis imperfecta (absence of the enamel cap) associated with short trunk and brachyolmia-like anomalies (platyspondyly with short pedicles, narrow intervertebral and interpedicular distances, rectangular-shaped vertebrae with posterior scalloping, herniation of the nuclei, and broad femoral necks). Inheritance appeared to be autosomal recessive. The girl was 141 cm tall at age 16, with an arm span of 142 cm, a sitting height of 72 cm, and short hands. She was completely edentulous, all teeth having to be removed within a year of eruption. At the age of 12 years, the brother was 133 cm tall with sitting height of 63 cm and arm span of 134 cm. The permanent teeth were yellowish and almost completely lacking in enamel cap.

Bertola et al. (2009) described 3 affected patients (2 sibs and 1 unrelated patient), from consanguineous matings, presenting with brachyolmia with enamel defects. In the first family, the older brother had oligodontia and enamel hypoplasia; the younger brother had widely spaced permanent teeth, enamel hypoplasia, agenesis of both inferior second premolars and retention of their deciduous. In the second family, the patient had retarded eruption of permanent teeth, amelogenesis imperfecta, and taurodontic pulp chambers.

Inheritance

Bertola et al. (2009) suggested autosomal recessive inheritance of this disorder because of consanguinity and a negative family history for any bone or dental abnormalities in their families.

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Short stature

HEAD AND NECK: [Teeth]; Oligodontia; Amelogenesis imperfecta

SKELETAL: Delayed bone age; [Spine]; Platyspondyly; Thick, short pedicles; Narrow intervertebral spaces; Posterior scalloping; Herniated intervertebral nuclei; Narrow interpedicular space
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Brachyolmia-amelogenesis imperfecta syndrome

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

Autosomal recessive brachyolmia-amelogenesis imperfecta syndrome is an exceedingly rare form of brachyolmia (see this term), characterized by mild platyspondyly, broad ilia, elongated femoral necks with coxa valga, scoliosis, and short trunked short stature associated with amelogenesis imperfecta (see this term) of both primary and permanent dentition. Expert reviewer(s) Dr Gen NISHIMURA Last update: March 2015
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Autosomal recessive omodysplasia

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: gpc6, cd44
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Omodysplasia

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: gpc6, cd44

Omodysplasia is a rare skeletal dysplasia characterized by severe limb shortening and facial dysmorphism. Two types of omodysplasia have been described: an autosomal recessive or generalized form (also referred to as micromelic dysplasia with dislocation of radius) marked by severe micromelic dwarfism with predominantly rhizomelic shortening of both the upper and lower limbs, and an autosomal dominant form in which stature is normal and shortening is limited to the upper limbs. In total, less than 40 cases of omodysplasia have been described in the literature so far, with the majority of reported cases concerning the autosomal recessive form of the disease. The facial dysmorphism is characterized by frontal bossing, a depressed nasal bridge with a short nose and a long and prominent philtrum. Decreased mobility of the elbows and knees is also a common feature. Other less frequent manifestations include midline hemangiomas, congenital heart defects, craniosynostosis and cryptorchidism in males. The etiology remains unknown but a paternally-inherited paracentric inversion of 15q13 to q21.3 has been detected in one family. Diagnosis is based on the clinical and radiological phenotype with major radiological findings including shortening and club-like tapering of the humeri and femora, proximal radioulnar diastasis and proximal radial head dislocation. Although the hands are generally considered to be normal in omodysplasia, short first metacarpals have been reported in the majority of patients with the autosomal dominant form. The differential diagnosis for the autosomal recessive form should include diastrophic dysplasia, atelosteogenesis and Larsen syndrome (see these terms), whereas the major differential diagnosis for the autosomal dominant form is Robinow syndrome (see this term). Genetic counseling should be recommended. For affected families, detection of long bone anomalies by ultrasonography may allow prenatal diagnosis as early as at 13 weeks of gest...
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Brachyolmia type 1, Toledo type

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

Brachyolmia type 1, Toledo type is an autosomal recessive form of brachyolmia (see this term), a group of rare genetic skeletal disorders, and is characterized by short stature, short trunk, and platyspondyly, as well as corneal opacities. Last update: January 2014

Chondrodysplasia, lethal, with long bone angulation and mixed bone density

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

Description

Seller et al. (1996) described a sporadic case of lethal chondrodysplasia in a male fetus born of first-cousin Caucasian parents. The fetus manifested an absence of ossification of the skull vault and vertebral bodies in the cervical and thoracic regions, platyspondyly in the lumbar region, and short angulated ulnae, radii, femora, tibiae, and fibulae. The fetus also presented sclerosis of scapulae and iliac bones, and humeri with mixed sclerosis affecting the metaphyses and with lysis affecting predominantly the diaphyses. Seller et al. (1996) suggested that this fetus represents a 'new' autosomal recessive form of lethal chondrodysplasia.

Symptoms

Skel: Lethal chondrodysplasia

Limbs: Short angulated ulnae, radii, femora, tibiae, and fibulae

Radiology: Absent ossification of skull vault; Absent ossification of cervical and thoracic vertebral bodies; Lumbar platyspondyly; Sclerosis of scapulae and iliac bones; Mixed sclerosis of humeral metaphyses; Humeral diaphyseal lysis

Inheritance: Autosomal recessive
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Brachyolmia

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: trpv4, papss2

Brachyolmia is a rare, clinically and genetically heterogeneous group of bone disorders characterized by short trunk, mild short stature, scoliosis and generalized platyspondyly without significant abnormalities in the long bones. The prevalence of brachyolmia is not known, but the disorder is probably under-recognized. Fewer than 100 cases have been reported to date. Cases have been reported in various ethnic groups. However, most cases with the Hobaek/Toledo type reported so far were of Turkish origin. Four types of brachyolmia have been described: autosomal recessive brachyolmia, Hobaek/Toledo type, autosomal recessive brachyolmia-amelogenesis imperfecta syndrome, autosomal dominant brachyolmia, and autosomal recessive brachyolmia, Maroteaux type (see these terms). The age of onset is generally in childhood with short stature becoming more evident with age. The clinical manifestations are generally mild to moderate, with minor physical functional repercussions. Some patients report non-specific back pain. The disorder is not associated with intellectual disability. AR brachyolmia, Hobaek/Toledo type is characterized by short-trunked short stature with platyspondyly and scoliosis. Corneal opacities and precocious calcification of costal cartilage occur in rare cases. In AR brachyolmia-amelogenesis imperfecta syndrome, short-trunked short stature is associated with platyspondyly and enamel abnormalities. AD brachyolmia is a more severe form with significant short-trunked short stature, platyspondyly and kyphoscoliosis. Lastly, presumably autosomal recessive brachyolmia, Maroteaux type is a vague entity that has not been well characterized but may involve short trunk/short stature, generalized platyspondyly and rounding vertebral bodies. Mutations in the PAPSS2 gene (10q24) have been found in patients with AR brachyolmia, Hobaek/Toledo type, and in the TRPV4 gene (12q24.1) in patients with AD brachyolmia. Precise pathogenesis is not well understood. Clinica...
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Spondyloepiphyseal dysplasia tarda, Kohn type

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

Spondyloepiphyseal dysplasia tarda, Kohn type is characterized by short trunk dwarfism, progressive involvement of the spine and epiphyses and mild-to-moderate intellectual deficit. The syndrome has been described in three daughters born to healthy consanguineous parents. The skeletal disorder usually manifests in late childhood. Typical radiographical features include platyspondyly, abnormal lumbar vertebrae and degenerative large joint changes. Autosomal recessive transmission has been suggested. Last update: September 2009
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Spondyloepiphyseal dysplasia tarda with mental retardation

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

Clinical features

In 3 daughters of healthy, consanguineous parents, Kohn et al. (1987) described spondyloepiphyseal dysplasia associated with mild to moderate mental retardation. A paternal aunt, married to a first cousin, was said to have a similarly affected offspring. Radiologic studies showed, in addition to an anterior tongue-like protrusion of the lumbar vertebral bodies and platyspondyly, absent dens epistrophei, flared iliac bones ('Mickey Mouse ear-shaped'), and short sacrosciatic notch. Bilateral deformity of the acetabulum with left femoral subluxation and bilateral coxa valga were present. The femoral necks were unusually narrow.

Inheritance

The pedigree pattern in the family with SEDT and mental retardation reported by Kohn et al. (1987) was consistent with autosomal recessive inheritance.

Symptoms

Skel: Spondyloepiphyseal dysplasia

Neuro: Mild to moderate mental retardation

Radiology: Anterior tongue-like protrusion of lumbar vertebral bodies; Platyspondyly; Absent dens epistrophei; Flared iliac bones ('Mickey Mouse ear-shaped'); Short sacrosciatic notch; Acetabular deformity with femoral subluxation and coxa valga; Unusually narrow femoral necks

Inheritance: Autosomal recessive
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Cardiomyopathy - cataract - hip spine disease

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

Cardiomyopathy - cataract - hip spine disease describes the extremely rare triad of dilated cardiomyopathy, premature cataract, and articular disease of the hips and spine characterized by hip joint degeneration, irregular intervertebral disks, and platyspondyly. The ocular abnormalities are often the first symptoms to arise. There have been no further descriptions in the literature since 1985. Last update: January 2014
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Spondylocamptodactyly

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

Clinical features

Lizcano-Gil et al. (1995) reported a family in which 5 members in 3 generations had camptodactyly (see 114200) in association with flattened cervical vertebral bodies and scoliosis. They suggested that the inheritance was autosomal dominant; however, the 3 affected females in the third generation were the products of a consanguineous marriage. The possibility of earlier consanguinity makes autosomal recessive inheritance with pseudodominance a possibility.

Symptoms

Limbs: Camptodactyly. Flexion contractures of proximal interphalangeal joints.

Spine: Scoliosis.

Radiology: Flattened cervical vertebral bodies.

Inheritance: Autosomal dominant vs. autosomal recessive with pseudodominance.
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Spondylocamptodactyly syndrome

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

Spondylo-camptodactyly syndrome is characterized by camptodactyly, flattened cervical vertebral bodies and variable degrees of thoracic scoliosis. This syndrome has been described in five members from three generations of one family. Inhertitance is thought to be autosomal dominant or autosomal recessive with pseudodominance. Last update: September 2009
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Spondylometaphyseal dysplasia, axial

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

Clinical features

Ehara et al. (1997) presented a previously undescribed, probably autosomal recessive skeletal dysplasia characterized by mild platyspondyly, small thorax with cupping of the anterior ends of the ribs, irregular proximal femoral metaphyses, and lacy appearance of the iliac wings. The 3 patients were a Korean brother and sister and an unrelated Japanese child. Retinitis pigmentosa and optic atrophy were associated findings. The lacy appearance of the iliac crest is a feature also of Dyggve-Melchior-Claussen syndrome (223800), but Ehara et al. (1997) pointed out that the severe epiphyseal dysplasia of the proximal femurs and marked platyspondyly with particular double-hump appearance of the vertebral bodies seen in DMC syndrome were not present in their patients. Other rare forms of SMD could be excluded, they thought. The parents in neither case were consanguineous.

Isidor et al. (2010) reported 2 unrelated boys with short stature, femoral metaphyseal abnormalities, platyspondyly, and retinitis pigmentosa. The first boy, born of consanguineous parents, was evaluated at 7.5 years of age for short stature and found to have frontal bossing, a narrow bell-shaped thorax with prominent sternum, and rhizomelic shortening of the limbs. Radiologic examination showed moderate platyspondyly with ovoid vertebral bodies and enlarged short ribs, irregular iliac crest, and very abnormal femoral metaphyses with short and enlarged femoral neck. Bone age was moderately delayed. By 14.8 years of age, he had developed photophobia; ophthalmoscopy showed bilateral pale papillae, normal maculae, and diffuse atrophy of the pigmentary epithelium. Goldman visual fields were normal, whereas electroretinography (ERG) showed a 50% decrease in scotopic white and red waves. Cerebral MRI showed slight bilateral optic nerve atrophy. The other boy, born of healthy nonconsanguineous parents, was evaluated at 6.5 years of age for growth failure and noted to have delayed bone age, telecanthus and hypertelorism with antimongoloid palpebral fissures, slight eversion of the inferior eyelids, and short nose with anteverted nares. The thorax was very narrow with a bell-shaped thoracic cage, and he had rhizomelic shortening of the limbs; radiography showed spondylometaphyseal dysplasia, predominating in the pelvis and femoral neck, with lacy iliac wings. Ophthalmologic examination revealed bila...

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Short stature

HEAD AND NECK: [Eyes]; Retinitis pigmentosa; Optic atrophy; Nystagmus

RESPIRATORY: [Lung]; Pneumonia, recurrent

CHEST: [External features]; Small chest; [Ribs, sternum, clavicles, and scapulae]; Anterior cupping of ribs; Widened anterior ribs

SKELETAL: Spondylometaphyseal dysplasia; [Spine]; Mild platyspondyly; [Pelvis]; Lacy iliac wings; Narrow sacrosciatic notch; Irregular proximal femoral metaphyses; Short femoral necks; Coxa vara
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Spondylometaphyseal dysplasia - cone-rod dystrophy

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: pcyt1a

This syndrome is characterised by the association of spondylometaphyseal dysplasia (marked by platyspondyly, shortening of the tubular bones and progressive metaphyseal irregularity and cupping), with postnatal growth retardation and progressive visual impairment due to cone-rod dystrophy. So far, it has been described in eight individuals. Transmission appears to be autosomal recessive. Last update: March 2007
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Occipital horn syndrome

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: atp7a, lox, dnah8

Description

A number sign (#) is used with this entry because occipital horn syndrome (OHS) is caused by mutation in the gene encoding Cu(2+)-transporting ATPase, alpha polypeptide (ATP7A; 300011). Menkes syndrome (309400) is caused by mutation in the same gene.Occipital horn syndrome is a rare connective tissue disorder characterized by hyperelastic and bruisable skin, hernias, bladder diverticula, hyperextensible joints, varicosities, and multiple skeletal abnormalities. The disorder is sometimes accompanied by mild neurologic impairment, and bony abnormalities of the occiput are a common feature, giving rise to the name (summary by Das et al., 1995).

Clinical features

Lazoff et al. (1975) described an unusual syndrome in an 11-year-old male and 2 maternal uncles. Bony 'horns,' symmetrically situated on each side of the foramen magnum and pointing caudad, were demonstrable radiographically. A lifelong history of frequent loose stools, obstructive uropathy requiring in 1 uncle ileal loop diversion, and mild mental retardation were other features. Some suspicion that a relative through the maternal grandfather had the same condition (which could not be confirmed because of lack of cooperation) meant that autosomal dominant inheritance with reduced penetrance could not be excluded.

Byers et al. (1976) found deficiency of lysyl oxidase in affected males in a family with apparent X-...

Symptoms

INHERITANCE: X-linked recessive

HEAD AND NECK: [Head]; Persistent, open anterior fontanel; [Face]; Long, thin face; High forehead; Long philtrum; [Nose]; Hooked nose; [Mouth]; High-arched palate; [Neck]; Long neck

CARDIOVASCULAR: [Vascular]; Orthostatic hypotension; Elongated, tortuous carotid arteries; Intracranial arterial narrowing

CHEST: [External features]; Narrow shoulders; Narrow chest; [Ribs, sternum, clavicles, and scapulae]; Short, broad clavicles; Pectus excavatum; Pectus carinatum; Short, broad ribs

ABDOMEN: [Gastrointestinal]; Chronic diarrhea; Hiatal hernia

GENITOURINARY: [Kidneys]; Hydronephrosis; [Ureters]; Ureteral obstruction; [Bladder]; Bladder diverticula; Bladder rupture

SKELETAL: Joint laxity; Osteoporosis; [Skull]; Occipital horn exostoses; [Spine]; Kyphosis; Mild platyspondyly; [Pelvis]; Coxa valga; Pelvic exostoses; [Limbs]; Short humeri; Genu valgum; Limited elbow extension; Limited knee extension; [Hands]; Capitate-hamate fusion; [Feet]; Pes planus

SKIN, NAILS, HAIR: [Skin]; Soft skin; Mildly extensible skin; Loose, redundant skin; Easy bruisability; [Hair]; Coarse hair

NEUROLOGIC: [Central nervous system]; Low-normal IQ

NEOPLASIA: Bladder carcinoma

LABORATORY ABNORMALITIES: Decreased serum copper; Decreased ceruloplasmin

MOLECULAR BASIS: Caused by mutation in the ATPase, Cu++ transporting, alpha polypeptide gene (ATP7A, 300011.0002)
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Pseudodiastrophic dysplasia

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

Pseudodiastrophic dysplasia is characterized by rhizomelic shortening of the limbs and severe clubfoot deformity, in association with elbow and proximal interphalangeal joint dislocations, platyspondyly, and scoliosis. It has been described in about 10 patients. An autosomal recessive inheritance has been suggested. Pseudodiastrophic dysplasia differs from diastrophic dysplasia (see this term) on the basis of clinical, radiographic, and histopathologic findings. Clubfoot can be treated by surgical therapy, and neonatal contractures and scoliosis can be relieved by physical therapy. Several of the reported patients died in the neonatal period or during infancy. Last update: January 2007
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Spondyloepimetaphyseal dysplasia, Pakistani type

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Associated genes: papss2
Spondyloepimetaphyseal dysplasia, Pakistani type is a form of spondyloepimetaphyseal dysplasia involving PAPSS2 (also known as "ATPSK2"). The condition is rare.

Genetics

This condition is inherited in an autosomal recessive fashion. It is due to mutations in the Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 (PAPSS2) gene which is located on the long arm of chromosome 10 (10q22-q24).

Clinical features

This condition is a skeletal dysplasia characterized by short stature, mild brachydactyly, kyphoscoliosis, abnormal gait, enlarged knee joints, precocious osteoarthropathy, platyspondyly, delayed epiphyseal ossification, mild metaphyseal abnormalities, short stature and short and bowed legs. Intelligence is normal. Some patients may manifest premature pubarche and hyperandrogenism. Other features that may form part of the syndrome include precocious costal calcification, small iliac bones, short femoral necks, coxa vara, short halluces and fused vertebral bodies.

Radiology

Radiographic features include delayed epiphyseal ossification at the hips and knees, platyspondyly with irregular end plates and narrowed joint spaces, diffuse early osteoarthritic changes (in the spine and hands), mild brachydactyly and mild metaphyseal abnormalities which predominantly involve the hips and knees.

History

This condition was first described in a large eight generation consanguineous Pakistani family. The causative mutation was identified in 1998.
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Autosomal dominant brachyolmia

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: trpv4

Autosomal dominant brachyolmia is a relatively severe form of brachyolmia (see this term), a group of rare genetic skeletal disorders, characterized by short-trunked short stature, platyspondyly and kyphoscoliosis. Degenerative joint disease (osteoarthropathy) in the spine, large joints and interphalangeal joints becomes manifest in adulthood. The precise prevalence of this form of brachyolmia is not known. About 30 cases have been reported. Patients with Brachyolmia type 3 generally have a normal birth weight and length. Affected individuals present with moderately short trunk/short stature and mildly short limbs in childhood. Kyphoscoliosis is common and sometimes severe. Adult patients develop degenerative joint disease in the spine, large joints and small joints of the hands and feet, which may cause significant musculoskeletal morbidity, such as chronic pain in the extremities and spine, and paresthesia. Final adult height is reported to be 155-168 cm (males) and 136-150 cm (females). The radiographic features include severe platyspondyly particularly in the cervical spine, elongated vertebral bodies (overfaced pedicles), broad ilia, and mild metaphyseal irregularity in the proximal femora. Carpal ossification may be mildly delayed, and mild brachydactyly may exist. Heterozygous mutations in the TRPV4 gene (12q24.11) are responsible for autosomal dominant brachyolmia. TRPV4 mutations are associated with other skeletal dysplasias, including lethal and nonlethal metatropic dysplasia, spondyloepiphyseal dysplasia Maroteaux type, and spondylometaphyseal dysplasia Kozlowski type (see these terms). Autosomal dominant brachyolmia falls into the mildest end of the TRPV4-associated skeletal dysplasia group. TRPV4 encodes a Ca-permeable, non-selective cation channel that participates in the regulation of osmotic sensitivity and mechanosensitivity. It remains to be explained how dysregulation of the cation channel causes the skeletal abnormalities. Genetic counse...
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Skeletal dysplasia, rhizomelic, with retinitis pigmentosa

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

Description

Megarbane et al. (2004) described what they considered to be a newly recognized autosomal recessive syndrome in a 4-year-old girl, the offspring of healthy first-cousin Lebanese parents. The features were severe pre- and postnatal short stature, low pitched voice, retinitis pigmentosa, photophobia, short neck, broad thorax, platyspondyly, rhizomelic shortening of the long bones, bilateral subluxation of the hips, advanced maturation of the epiphyses, and apparently normal intellectual development. Two subsequent pregnancies had ended in spontaneous abortion with polyhydramnios and severe growth retardation. Another daughter was alive and in good health.
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Goldblatt syndrome

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

Odontochondrodysplasia, also called Goldblatt syndrome, is a very rare syndrome associating chondrodysplasia with dentinogenesis imperfecta. To date, 11 patients have been reported. Chondrodysplasia is characterized by mesomelic limb shortening, joint laxity, platyspondyly with coronal clefts, brachydactyly and coxa valga. The affected patients have no intellectual deficit. The etiology is unknown. The condition is most probably hereditary, transmitted as an autosomal recessive trait. Expert reviewer(s) Dr Nicole MORICHON-DELVALLEZ Last update: May 2011
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Czech dysplasia, metatarsal type

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: col2a1

Czech dysplasia, metatarsal type is a form of skeletal dysplasia characterised by severe arthropathy beginning in childhood and hypoplasia/dysplasia of the third, fourth and/or fifth toes. So far, less than 20 patients have been reported, including multiple members of five families from the Czech Republic. Stature and intelligence are normal. Radiographs reveal platyspondyly, irregular vertebral endplates, deformed femoral heads, pelvic dysplasia and narrowed intervertebral spaces. Transmission is autosomal dominant and mutations in the COL2A1 gene have been detected in several of the reported patients. Expert reviewer(s) Dr Martine LE MERRER Last update: May 2008
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Czech dysplasia

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

What is Czech dysplasia?

Czech dysplasia is an inherited condition that affects joint function and bone development. People with this condition have joint pain (osteoarthritis) that begins in adolescence or early adulthood. The joint pain mainly affects the hips, knees, shoulders, and spine and may impair mobility. People with Czech dysplasia often have shortened bones in their third and fourth toes, which make their first two toes appear unusually long. Affected individuals may have flattened bones of the spine (platyspondyly) or an abnormal spinal curvature, such as a rounded upper back that also curves to the side (kyphoscoliosis). Some people with Czech dysplasia have progressive hearing loss.

How common is Czech dysplasia?

The prevalence of Czech dysplasia is unknown; at least 11 families have been affected. Most of these families reside in the Czech Republic.

What genes are related to Czech dysplasia?

Czech dysplasia is caused by a particular mutation in the COL2A1 gene. The COL2A1 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, which prevents bones and other connective tissues from developing properly. Read more about the COL2A1 gene.

How do people inherit Czech dysplasia?

Czech dysplasia is inherited in an autosomal dominant pattern, which means one copy of the altered COL2A1 gene in each cell is sufficient to cause the disorder. All known individuals with Czech dysplasia inherited the mutation from a parent with the condition.

Keywords

Czech dysplasia,Osteochondrodysplasias,Bone Diseases,Musculoskeletal Diseases,Bone Diseases, Developmental,Bones, muscles, and connective tissues,type II collagenopathy,COL2A1,COL2A1 gene,Czech dysplasia metatarsal type,progressive pseudorheumatoid dysplasia with hypoplastic toes,spondyloarthropathy with short third and fourth toes,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,inborn disorders,inborn diseases
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Brachyolmia, Maroteaux type

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: trpv4

Autosomal recessive brachyolmia, Maroteaux type is a relatively mild form of brachyolmia (see this term), a group of rare genetic skeletal disorders, characterized by short trunk/short stature, generalized platyspondyly and rounding of vertebral bodies. It remains unknown whether the phenotype represents a single disease entity or a heterogeneous group of mild skeletal dysplasias. The prevalence of this form of brachyolmia is not known. About 10 cases have been reported. Patients with brachyolmia, Maroteaux type are reported to have short stature/short trunk, scoliosis and generalized platyspondyly with rounding of the anterior and posterior vertebral bodies. The vertebral bodies show less elongation compared to those in patients with other types of the disorder (autosomal recessive brachyolmia, Hobaek/Toledo type, autosomal dominant brachyolmia; see these terms). Some cases are associated with precocious calcification of the cerebral falx and non-specific minor facial anomalies. Intellectual ability is normal. The etiology of this form of brachyolmia is not known. The causative gene mutation has not been identified. Brachyolmia, Maroteaux type is presumed to be autosomal recessive because of a few reported occurrences in siblings. For precise genetic counseling, however, it is essential to rule out mild skeletal dysplasias of autosomal dominant inheritance, such as mild cases with type 2 collagenopathy. Expert reviewer(s) Dr Gen NISHIMURA Last update: March 2015
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Spondyloepiphyseal dysplasia, maroteaux type

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: trpv4

Clinical features

A number sign (#) is used with this entry because of evidence that the Maroteaux type of spondyloepiphyseal dysplasia is caused by heterozygous mutation in the TRPV4 gene (605427).Doman et al. (1990) used the designation spondyloepiphyseal dysplasia (SED) of Maroteaux for a form of spondyloepiphyseal dysplasia with manifestations limited to the musculoskeletal system and with other features distinguishing it from Morquio syndrome of any type (253000, 253010, 252300), X-linked SED tarda (313400), brachyolmia (113500, 271530, 271630), and spondylometaphyseal dysplasia of Kozlowski (184252). Doman et al. (1990) reported affected father and son, aged 51 and 20 years, respectively, and affected mother and son. The patients were considered normal at birth. Platyspondyly is a feature, but there is no tongue-like deformity of the vertebral bodies in this disorder. Intelligence is normal and there is no clouding of the cornea or mucopolysacchariduria. Both hands and feet are short and stubby. The pelvic inlet is described as having a champagne-glass configuration, unlike the wine-glass-like configuration of the pelvic inlet in patients who have Morquio syndrome. Odontoid hypoplasia was not found. Genu valgum was present.

Nishimura et al. (2003) reported a Japanese mother and son and an unrelated 65-year-old man with spondyloepiphyseal dysplasia of Maroteaux. The adults had extremely short stature, brachydactyly, platyspondyly, rectangular vertebral bodies with irregular endplates, epiphyseal hypoplasia of the large joints, and iliac hypoplasia. The man had myeloradiculopathy necessitating neurosurgery. The affected child had short stature and brachydactyly with characteristic spine radiographic findings. None of the patients had mutations in the COL2A1 gene (120140), which excluded a diagnosis of spondyloperipheral dysplasia (271700). Nishimura et al. (2003) suggested that platyspondyly and brachydactyly are much more severe in SED of Maroteaux than in spondyloperipheral dysplasia.

Megarbane et al. (2004) reported a patient with characteristic features of spondyloepiphyseal dysplasia of Maroteaux. The 11-year-old girl, who was of normal intelligence, was the only child of nonconsanguineous parents, and appeared normal at birth. Clinical features included short stature, head positioned in hyperextension, mild arched palate, prominent joints, limited elbow movements, hyperextensible wrists and fingers, brachydactyly, broad thorax, pectus carinatum, short trunk, genu valgum, and flat feet. A radiographic skeletal survey revealed generalized osteoporosis, platyspondyly, thoracic kyphoscoliosis, small and square iliac wing...

Symptoms

Skel: Spondyloepiphyseal dysplasia; Platyspondyly

Neuro: Normal intelligence

Eyes: No corneal clouding

Limbs: Short and stubby hands and feet; Genu valgum

Radiology: Champagne-glass configuration of pelvic inlet

Lab: No mucopolysacchariduria

Inheritance: Autosomal dominant
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Spondyloepiphyseal dysplasia tarda, autosomal recessive

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

Description

Golding (1935) and Klenerman (1961) described 2 sons and a daughter, of a first-cousin marriage, who showed short stature, flat vertebrae, and severe hip disease. In the proband, symptoms in the back began at 15 years, followed by symptoms referable to the hips. Multiple loose bodies were removed from various joints of 1 sib--18 from the right hip at about age 26, several from the left elbow at age 28, and 30 from the left hip at age 33. The proband was about 52 years old at the time of Klenerman's report. Severe osteoarthritis of the hips was a feature. The authors suggested a relationship to Morquio-Brailsford chondroosteodystrophy, but this seems doubtful.

Martin et al. (1970) described 2 brothers, offspring of a second-cousin marriage, with platyspondyly, flattening of the metatarsal and metacarpal beads, and symmetrical polyarticular osteoarthritis. No beta-2-globulin was demonstrated in their sera. The patients were natives of the Magdalen Islands in the Gulf of St. Lawrence and many others of that population were found to have either absence or relative deficiency of beta-2-globulin (Martin et al., 1970). Hence, it may represent a separate genetic trait.

Carter and Sutcliffe (1970) pointed out that autosomal dominant, autosomal recessive, and X-linked forms of spondyloepiphyseal dysplasia are known.

Symptoms

Growth: Short stature

Radiology: Platyspondyly

Joints: Severe osteoarthritis of hips; Multiple loose bodies in various joints; Flattened metatarsal and metacarpal heads; Symmetrical polyarticular osteoarthritis

Lab: Deficiency of beta-2-globulin

Inheritance: Autosomal recessive; other autosomal dominant, autosomal recessive, and X-linked forms of spondyloepiphyseal dysplasia are known
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Rhizomelic dysplasia, patterson-lowry type

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

Description

Patterson and Lowry (1975) described a sporadic case of rhizomelic shortening of the limbs with predominant involvement of the humeri in an 86-year-old man. This patient also had deformity of the humeral heads and coxa vara. Williams et al. (1995) reported another sporadic case with similar clinical manifestations in a mentally normal 5-year-old boy. Platyspondyly, anomalous segmentation of the proximal humeral metaphyses, foreshortening and bowing of the humeri, brachydactyly, and brachymetacarpalia were the main roentgenologic abnormalities.

Kamoda et al. (2001) reported a third possible case of the Patterson-Lowry type of rhizomelic dysplasia. Franceschini et al. (2004) reported 2 further patients, 1 Albanian and 1 Romanian. The disorder in these unrelated patients was characterized by very short humeri, coxa vara with proximal femoral epiphyseal involvement, and short metacarpals, metatarsals, and phalanges. Franceschini et al. (2004) suggested that despite the clinical and radiologic variability, the unique proximal metaepiphyseal appearance of the humeri makes the syndrome easily identifiable. The changes in the humeri were widening of proximal metaphyses, striking flattening of the proximal epiphyses, and lateral bulging of proximal diaphyses. All reported cases had been sporadic and in no instance was parental consanguinity identified. Both males and females had been affected.

Symptoms

Limbs: Rhizomelic short limbs; Short humeri; Deformed humeral heads; Coxa vara

Radiology: Platyspondyly; Anomalous segmentation of proximal humeral metaphyses; Short bowed humeri; Brachydactyly; Brachymetacarpalia

Inheritance: ? Autosomal recessive
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Spondyloepimetaphyseal dysplasia with abnormal dentition

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

Clinical features

The spondyloepimetaphyseal dysplasias are disorders characterized by involvement of the epiphyses, metaphyses, and vertebral bodies. Rao et al. (1997) described an apparently new form of SEMD, inherited as an autosomal recessive, and associated with abnormal dentition. In addition to generalized platyspondyly with epiphyseal and metaphyseal involvement, a 16-year-old girl and her 11-year-old brother showed thin tapering fingers with accentuated palmar creases and abnormal dentition (oligodontia and pointed incisors). The parents were first cousins.

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Proportionate short stature

HEAD AND NECK: [Eyes]; Blue sclerae; [Teeth]; Oligodontia (reduced number of molars and premolars); Pointed lower central incisors; Discolored lateral incisors; Wide gap between upper and lower central incisors

SKELETAL: Spondyloepimetaphyseal dysplasia; [Spine]; Platyspondyly; Irregular vertebral endplates; [Pelvis]; Narrow iliac wings; Short, broad femoral necks; [Limbs]; Genu valgum; Mildly flared irregular metaphyses; Small, flat irregularly ossified epiphyses; [Hands]; Thin, tapering fingers; Accentuated palmar creases; Fifth finger camptodactyly; Pseudoepiphyses (1st and 5th metacarpals)

SKIN, NAILS, HAIR: [Skin]; Dry palmar skin

NEUROLOGIC: [Central nervous system]; Normal intelligence
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Osteoarthritis with mild chondrodysplasia

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

Mapping

A number sign (#) is used with this entry because of evidence that osteoarthritis with mild chondrodysplasia is caused by mutation in the COL2A1 gene (120140).In Finland, early-onset osteoarthrosis is relatively frequent and seems to run in certain families in an autosomal dominant pedigree pattern. In a large Finnish family with affected members in at least 5 generations, Vaisanen et al. (1987) found linkage with 2 RFLPs of the type II collagen locus on chromosome 12. The lod score was 1.7 with 1 marker and 1.4 with a second, both at theta = 0.0. Palotie et al. (1989) extended these observations, reporting a maximum lod score of 3.20 at theta = 0.0 in 2 families.

Molecular genetics

In a kindred described by Knowlton et al. (1990) with dominantly inherited generalized osteoarthritis associated with a mild chondrodysplasia, Ala-Kokko et al. (1990) identified an arg519-to-cys mutation of the type II collagen gene (120140.0003).

Symptoms

INHERITANCE: Autosomal dominant

GROWTH: [Height]; Decreased height compared to unaffected siblings

SKELETAL: Osteoarthritis (hips, knees, shoulders, wrists, hands); Joint stiffness; [Spine]; Irregular endplates; Mild platyspondyly; Schmorl's nodes; Anterior wedging; [Hands]; Enlarged MCP joints; Enlarged PIP and DIP joints; Heberden's nodes

MISCELLANEOUS: Onset of osteoarthritis in teens to early adulthood

MOLECULAR BASIS: Caused by mutation in the collagen II, alpha-1 polypeptide gene (COL2A1, 120140.0003)
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Epiphyseal dysplasia, multiple, with severe proximal femoral dysplasia

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

Clinical features

Jakkula et al. (2005) identified 3 patients with a strikingly similar severe early-onset dysplasia of the proximal femurs with almost complete absence of the secondary ossification centers and wide, short femoral necks with irregular metaphyses. All 3 cases had coxa vara. Spinal changes, present in 2 of the patients, were significantly milder than those usually seen in spondyloepiphyseal dysplasia (see 183900); the vertebrae were normal in shape and the epiphyseal changes dominated. Jakkula et al. (2005) suggested that these patients had a novel form of multiple epiphyseal dysplasia.

Inheritance

One patient reported by Jakkula et al. (2005) had a family history consistent with autosomal dominant inheritance.

Molecular genetics

- Exclusion Studies

In none of the patients reported by Jakkula et al. (2005) was a mutation found in the COMP (600310), DTDST (606718), or MATN3 (602109) genes.

Symptoms

INHERITANCE: Autosomal dominant

GROWTH: [Height]; Short stature (<3rd percentile)

SKELETAL: [Spine]; Mild irregularity of vertebral bodies; Mild platyspondyly; [Pelvis]; Arthralgia (hip); Limited hip rotation; Marked deformity of or absent proximal femoral epiphyses; Short, wide femoral neck; Coxa vara; Irregular proximal femoral metaphyses; [Limbs]; Arthralgia (knee); Genua valga; Normal patella; Mildly flattened distal femoral epiphyses; [Hands]; Flared metaphyses (distal femurs and distal tibiae)

MISCELLANEOUS: Onset of symptoms in early childhood
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Fetal akinesia deformation sequence

Retrieved: 27-07-2015
Source: GARD (Original article)
Associated genes: rapsn, dok7, gbe1, chrng

Fetal akinesia deformation sequence

Fetal akinesia deformation sequence (FADS) is a condition characterized by decreased fetal movement (fetal akinesia) as well as intra-uterine growth restriction (IUGR), multiple joint contractures (arthrogryposis), facial anomalies, underdevelopment of the lungs (pulmonary hypoplasia) and other developmental abnormalities. It is generally accepted that this condition is not a true diagnosis or a specific syndrome, but rather a description of a group of abnormalities resulting from fetal akinesia. About 30% of affected individuals are stillborn; many liveborn infants survive only a short time due to complications of pulmonary hypoplasia. FADS may be inherited in an autosomal recessive manner in some cases and may sometimes be caused by mutations in the RAPSN or DOK7 genes
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Junctional epidermolysis bullosa - pyloric atresia

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

Junctional epidermolysis bullosa with pyloric atresia is a severe subtype of junctional epidermolysis bullosa (JEB, see this term) characterized by generalized blistering at birth and congenital atresia of the pylorus and rarely of other portions of the gastrointestinal tract. Prevalence is unknown. More than 100 cases have been reported worldwide. Skin manifestations include severe blistering, atrophic scarring, and nail dystrophy. Congenital absence of skin (aplasia cutis congenita) is present in approximately 20% of cases, and ear anomalies are also relatively common. The manifestations of pyloric atresia include vomiting, abdomen distension, and an absence of stools. Patients present oral cavity involvement and enamel hypoplasia. Other extracutaneous manifestations include involvement of the respiratory, gastrointestinal and genitourinary tracts. In particular, genitourinary malformations and acquired genitourinary abnormalities (polypoid bladder wall lesions, hemorrhagic cystitis, urethral strictures) are relatively frequent and characteristic. Growth delay and anemia, secondary to the extensive cutaneous and mucosal lesions, are common. Polyhydramnios, secondary to pyloric atresia, is usually present in pregnancies with an affected fetus. Some patients with an identical presentation have been found to have intraepidermal rather than intra-lamina lucida blister formation, necessitating their inclusion under the rarer subtypes of EB simplex rather than under junctional EB. The condition is caused by mutations in either of the genes encoding the two subunits of alpha6-beta4 integrin, ITGA6 (2q31.1) and ITGB4 (17q11-qter). Diagnosis in neonates is suspected based on clinical findings of skin fragility and gastric outlet obstruction. In addition to the finding of a cleavage plane located within the lamina lucida of the cutaneous basement membrane zone by immunofluorescence antigen mapping and/or transmission electron microscopy, a negative or highly reduce...
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Brachyolmia type 1, Hobaek type

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

Autosomal recessive brachyolmia, Hobaek/Toledo type is a form of brachyolmia (see this term), a group of rare genetic skeletal disorders, characterized by short-trunked short stature with platyspondyly and scoliosis. Corneal opacities and precocious calcification of the costal cartilage are rare syndromic components. Premature pubarche may occur. The precise prevalence of this form of brachyolmia is not known. About 20 cases have been reported. Cases have been reported in various ethnic groups (Japan, Korea, Turkey), sometimes related to consanguineous unions. However, a majority of cases reported so far were of Turkish origin. Patients with autosomal recessive brachyolmia, Hobaek/Toledo type generally have a normal birth weight and length. Platyspondyly is present in early childhood but patients usually come to medical attention in late childhood or early puberty as a result of stunted growth and short trunk. The radiographic features include platyspondyly with rectangular vertebral bodies and irregular end plates, broad ilia, short femoral neck, and broad proximal interphalangeal joints. Longitudinal striations in the femoral neck are occasionally seen. Precocious calcifications of the costal cartilage are described. The condition is described as relatively benign with the exception of mild non-specific backache and mild scoliosis beginning in young adulthood. However, reports are limited about the final outcome of musculoskeletal morbidity. Mental status and facies are reported to be normal. Some patients are reported to have peripheral punctuate opacities in the cornea found on slit lamp examination (formerly Toledo type). A number of different mutations in the PAPSS2 gene (10q23.2-q23.3) have been reported in affected patients. PAPPS2 encodes PAPS (3'-phosphoadenosine 5'-phosphosulfate) synthase 2. PAPSS2 mutations were also reported to cause two other disorders: spondyloepimetaphyseal dysplasia, Pakistani type (see this term), and spondylodysplasia an...
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Spondyloepiphyseal dysplasia tarda, autosomal dominant

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

Clinical features

Felman (1969) described a black father and his son and daughter with epiphyseal and vertebral dysplasia producing severe scoliosis and truncal shortening as well as complete destruction of the femoral capital epiphyses and necks. The hands and feet were short and stubby. Clinically and radiologically the patients were normal at birth.

Rubin (1964) presented (Figs. 7.9-7.14) an instructive family in which platyspondyly accompanied changes in the epiphyses in the limbs.

The family reported by Moldauer et al. (1962) had 7 affected persons in 3 generations with no male-to-male transmission. There may be more than one dominant form of spondyloepiphyseal dysplasia distinct from the pseudoachondroplastic types. It is clear, however, that there is at least one form. These cases have too much platyspondyly for the condition to be multiple epiphyseal dysplasia and the involvement of the bones of the limbs is not severe enough to fall into one of the pseudoachondroplasia groups.

Barber et al. (1984) reported a family that came to attention through a 54-year-old woman admitted to hospital for her second total hip joint replacement. In 5 sibships of 3 generations a skeletal dysplasia thought to represent autosomal dominant SED tarda was found. The mean height of affected and unaffected persons was the same: 164 cm; however, all affected persons had shorter trunk and longer legs than unaffected persons (mean upper-to-lower-segment ratio 0.83 against 0.95 in the unaffected). All affected persons had bilateral hip pain, and pain and stiffness in the back, knees, shoulders, and elbows also figured prominently. Symptoms began at an age ranging from 2 to 20 years; stiff gait usually preceded pain. Perthes disease, bilateral congenital dislocation of the hip, traumatic synovitis of the right hip and knees, and bone fragments from osteochondritis dissecans had been diagnosed in various affected persons. By x-ray, affected persons showed platyspondyly, irregularity of the femoral head (in childhood) and degenerative changes therein (in adulthood), and moderately severe degenerative changes in the joints of the hands. The family reported by Diamond (1970) was probably of this type.

Schantz et al. (1988) described this f...

Symptoms

INHERITANCE: Autosomal dominant

GROWTH: [Height]; Short trunk, not evident at birth; Reduced upper- to lower-body segment ratio

CHEST: [External features]; Barrel-shaped chest

SKELETAL: [Spine]; Platyspondyly; Irregular end plates; Kyphoscoliosis (in some patients); Scoliosis (in some patients); Arthritis; [Pelvis]; Bilateral congenital hip dislocation (in some patients); Reduction in hip movement; Osteochondritis dessecans of the hip; Bilateral hip pain; [Limbs]; Osteochondritis dessecans of the shoulders, elbows, and knees; Arthritis; Bilateral knee pain; Stiff gait

MISCELLANEOUS: Progressive disease; Onset between 2 to 20 years
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Spondyloenchondrodysplasia

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: acp5

Description

Spondyloenchondrodysplasia is a rare skeletal dysplasia involving vertebral dysplasia and enchondroma-like lesions in the pelvis and long bones. The vertebral bodies show dorsally accentuated platyspondyly with disturbance of ossification. Clinical abnormalities such as short stature, rhizomelic micromelia, increased lumbar lordosis, barrel chest, facial anomalies, and clumsy movements may be present (Menger et al., 1989).

Also see spondyloenchondrodysplasia with immune dysregulation (SPENCDI; 607944), which is caused by mutation in the ACP5 gene (174610). It has been suggested by some that the various clinical manifestations observed in association with SPENCD may be pleiotropic manifestations of a single nosologic entity defined by the presence of typical spondylar and metaphyseal changes (see Renella et al., 2006).

Clinical features

Schorr et al. (1976) described enchondromatosis, similar to that of Ollier disease (166000), in association with platyspondyly in 2 sons of first-cousin parents of Iraqi Jewish background. Both boys had short stature and normal intelligence.

Spranger et al. (1978) identified 6 types of enchondromatosis: Ollier disease, Maffucci syndrome (614569), metachondromatosis (156250), the disorder in the patients of Schorr et al. (1976), and 2 other forms represented by patients they reported. There was no evidence of a genetic basis of the latter 2 types.

Sauvegrain et al. (1980) described 2 patients with enchondromatosis with spinal involvement.

Frydman et al. (1986) studied 4 cases. The height of the patients was more than 3 SDs below the mean. Kyphoscoliosis with flat vertebrae and with 'cystic' radiolucencies in the posterior part of the bodies was observed. The metaphyses of long bones showed symmetric radiolucencies that extended into the shafts with sclerotic changes in the diaphyses. The proximal fibula and distal ulna were more severely affected than the corresponding areas of the tibia and radius. Frydman et al. (1990) noted that spastic quadriplegia was also present in the patient of Chagnon et al. (1985) and patient 4 of Menger et al. (1989). In addition, Frydman et al. (1990) suggested that mental retardation, which was found in their patient 5 as well as patient 3 of Sauvegrain et al. (1980) and patient 1 of Menger et al. (1989), might be another variable manifestation of the syndrome.

Menger et al. (1989) reported 4 patients, 3 of whom were members of 1 family containing complex consanguinity. They pointed to the 2 cases reported by Gustavson e...

Symptoms

Skel: Enchondromatosis; Kyphoscoliosis; Increased lumbar lordosis

Neuro: Variable mental retardation; Spasticity; Progressive spastic quadriparesis

Growth: Short stature; Short trunk; Short limbs

Radiology: Platyspondyly; Posterior vertebral body radiolucencies; Symmetric radiolucencies in long bone metaphyses; CNS calcifications, esp. basal ganglia, on CT scan

Inheritance: Autosomal recessive

Chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: hdac6

Clinical features

A number sign (#) is used with this entry because of evidence that this form of X-linked dominant chondrodysplasia is caused by heterozygous mutation in the HDAC6 gene (300272) on Xp11.23. One such family has been reported.Chassaing et al. (2005) reported a 4-generation family segregating an apparent X-linked dominant chondrodysplasia, in which 4 males and 6 females were affected. Features seen in the affected males included intrauterine growth retardation and hydrocephaly, macrocephaly, frontal bossing, microphthalmia, small low-set ears, and short flat nose. Radiography revealed macrocephaly with poor mineralization of the skull, severe platyspondyly, thin ribs, with only 11 rib pairs in 2 of the male patients, hypoplasia of the iliac wings, poor ossification of the pubis, distinctive metaphyseal cupped metacarpals, metatarsals, and phalanges, and hypoplastic calcaneus. Microscopic examination of the bones in 3 male patients showed similar anomalies, including severe flattening of the anlage of vertebral bodies, which were poorly delimited and under-ossified, whereas the intervertebral disks were thick with abnormal craniocaudal orientation of the fibroblasts. Resting cartilage showed sparse matrix and increased density of chondrocytes, which were irregular in size and shape and often had a fibroblastic appearance. The chondrocyte columns of the growth plate were small and rather irregular, with large cores of mineralized cartilage persisting among the primarily osseous trabeculae. Endochondral, diaphyseal, and endomembranous ossification of the cranium led to thickening of the trabecular bone, res...

Symptoms

INHERITANCE: X-linked dominant

GROWTH: [Height]; Short stature; [Other]; Intrauterine growth retardation

HEAD AND NECK: [Head]; Hydrocephaly; Macrocephaly; [Face]; Frontal bossing; [Ears]; Low-set ears; [Eyes]; Microphthalmia; [Nose]; Short nose; Flat nose

CHEST: [External features]; [Ribs, sternum, clavicles, and scapulae]; Thin ribs; 11 rib pairs in some male patients

SKELETAL: [Skull]; Macrocephaly; Poor mineralization of skull; [Spine]; Platyspondyly, severe; [Pelvis]; Hypoplasia of iliac wings (mild in carrier females); Poor ossification of pubis; [Limbs]; Rhizomelic shortening (in carrier females); [Hands]; Metaphyseal cupping of metacarpals; Metaphyseal cupping of phalanges; [Feet]; Hypoplastic calcaneus; Metaphyseal cupping of metatarsals; Metaphyseal cupping of phalanges

NEUROLOGIC: [Central nervous system]; Mental retardation, mild (in some females)

MISCELLANEOUS: Carrier females are less affected (short stature with rhizomelic shortening of limbs, mild body asymmetry, and mild mental retardation); Based on one report of a 4-generation family with 4 affected males and 6 affected females

MOLECULAR BASIS: Caused by mutation in the histone deacetylase 6 gene (HDAC6, 300272.0001)
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Platyspondylic dysplasia, Torrance type

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: col2a1

Platyspondylic lethal skeletal dysplasia (PLSD), Torrance type (PLSD-T) is a skeletal dysplasia characterised by severe limb shortening (short and broad long bones), platyspondyly with wafer-like vertebral bodies, short ribs with anterior cupping, severe hypoplasia of the lower ilia and radial bowing. Histological findings include slightly enlarged chondrocytes and hypercellularity. The prevalence is unknown. The disorder is transmitted as an autosomal dominant trait and is caused by mutations in the C-propeptide domain of the COL2A1 gene. Although PLSD-T is generally lethal, survival to adulthood has been reported in two families. Last update: June 2007
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Kniest-like dysplasia with pursed lips and ectopia lentis

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

Clinical features

Burton et al. (1986) described a skeletal dysplasia in 2 sibs, a male and female. The clinical and x-ray features resembled those observed in Kniest dysplasia (156550) and in Rolland-Desbuquois syndrome (see 224400) but important differences were noted, specifically, microstomia, pursed lips, and ectopia lentis. Histologically, scattered, dense patches consisting of collagen fibers 10 to 30 times broader than normal were seen throughout the cartilage matrix; the 'Swiss cheese' appearance characteristic of Kniest dysplasia was not observed. The lenses were dislocated downward in both patients. The parents were not related. The mouth resembled that of the whistling face syndrome (277720) but other features were different.

Lo et al. (1998) reported this disorder in a 2-year-old girl with characteristic clinical findings of short stature, joint stiffness, microstomia, and pursed lips. Platyspondyly with cervical kyphosis, but no coronal clefts, and bowing of the long bones were distinctive radiographic findings.

Spranger et al. (2000) restudied the sister and brother (then teenagers) reported by Burton et al. (1986). Both had developed severe myotonia and characteristic facial and skeletal features of Schwartz-Jampel syndrome (SJS1; 255800). The disorder in the sibs mapped to the SJS1 locus on chromosome 1p34-p36, supporting the claim that they had SJS1. Spranger et al. (2000) suggested that Burton disease may not exist as a nosologic entity.

Symptoms

INHERITANCE: Isolated cases

GROWTH: [Height]; Short stature

HEAD AND NECK: [Face]; Deep philtrum; [Eyes]; Ptosis; Ectopia lentis (in some patients); [Mouth]; Microstomia; Pursed lips; High-arched palate; [Neck]; Short neck

CHEST: [Ribs, sternum, clavicles, and scapulae]; Pectus carinatum; Lateral curving of inferior scapular angle; Normal ribs

SKELETAL: Joint stiffness (neck, shoulder, elbow, hips); Joint contractures (elbows and knees); [Spine]; Platyspondyly; Cervical kyphosis; No coronal clefts; [Pelvis]; Absent ossification of femoral capital epiphyses; [Limbs]; Large ossification centers; Femoral bowing; Tibial bowing

MISCELLANEOUS: Initial cases reclassified as having Schwartz-Jampel syndrome (SJS1, 255800)
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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

Retrieved: 27-07-2015
Source: Orphanet (original)
Associated genes: fkbp10, plod2, col1a1

Bruck syndrome is characterised by the association of osteogenesis imperfecta and congenital joint contractures. Prevalence is unknown but less than 40 cases have been reported in the literature so far. Features include osteoporosis and bone fragility, progressive joint contractures sometimes associated with pterygia, wormian bones, scoliosis due to vertebral deformities and short stature. Mental development is normal. The syndrome is genetically heterogeneous: the locus was mapped to chromosome 17p12 in one family (Bruck syndrome 1) but mutations in the PLOD2 gene (3q24) encoding telopeptide lysyl hydroxylase (Bruck syndrome 2) have been identified in other affected individuals. Transmission is autosomal recessive. Last update: July 2008


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: GARD (original)
Associated genes: pparg, htn1, tnfsf13b, apol2

Frontal fibrosing alopecia

Frontal fibrosing alopecia (FFA) is a form of lichen planus follicularis that is characterized primarily by slowly progressive hair loss (alopecia) and scarring on the scalp near the forehead. In some cases, the eyebrows, eye lashes and/or other parts of the body may be involved, as well. Although it has been suggested that FFA may be due to hormonal changes or an autoimmune response, the exact cause of this condition is not yet known. There is currently no cure for FFA; however, treatment with certain types of medications may stop or slow hair loss in some cases


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

Phaver syndrome is a very rare syndrome characterized by the association of limb Pterygia, Heart anomalies, Autosomal recessive inheritance, Vertebral defects, Ear anomalies and Radial defects. It has been described in two sibs. One of the sibs also had a myelomeningocele. The reported cases suggest the condition is hereditary with probable autosomal recessive inheritance. Last update: October 2010


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

Clinical features

Christian et al. (1975) described a mother and daughter with a syndrome of metacarpal and metatarsal asymmetry, platyspondyly, carpal and tarsal fusions, syndactyly, articular dysplasia, and platyspondyly. The most striking finding was asymmetry in length of the second metacarpals and metatarsals. For example, the daughter had short left second metacarpal and short right second metatarsal, their counterparts on the other side being abnormally long.

Garcia-Cruz et al. (1995) reported a mother and daughter with a similar syndrome characterized by proximal and distal flexion contractures in the phalanges and by brachydactyly, clinodactyly, and ulnar and radial subdislocations of the fingers. Radiologically, the second metacarpal in the daughter was longer than the other metacarpals, with bone-carpal fusion and flexion contractures of the fingers of both hands. Thoracolumbar kyphoscoliosis and malformed vertebrae with dyssegmentation of L2-L3, cuneiform shape of T12 and L1, asymmetry of the pelvic bones, and exostotic lesions in the proximal third of the tibia and the distal third of the femur were also noted. The authors referred to the disorder as Christian spondylodigital syndrome.

Symptoms

Skel: Metacarpal and metatarsal asymmetry; Carpal and tarsal fusions; Platyspondyly

Inheritance: Autosomal recessive


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)

Clinical features

Verloes et al. (1996) described an apparently 'new' form of skeletal dysplasia with amelogenesis imperfecta and platyspondyly in a brother and sister born of consanguineous parents. Hallmarks were amelogenesis imperfecta (absence of the enamel cap) associated with short trunk and brachyolmia-like anomalies (platyspondyly with short pedicles, narrow intervertebral and interpedicular distances, rectangular-shaped vertebrae with posterior scalloping, herniation of the nuclei, and broad femoral necks). Inheritance appeared to be autosomal recessive. The girl was 141 cm tall at age 16, with an arm span of 142 cm, a sitting height of 72 cm, and short hands. She was completely edentulous, all teeth having to be removed within a year of eruption. At the age of 12 years, the brother was 133 cm tall with sitting height of 63 cm and arm span of 134 cm. The permanent teeth were yellowish and almost completely lacking in enamel cap.

Bertola et al. (2009) described 3 affected patients (2 sibs and 1 unrelated patient), from consanguineous matings, presenting with brachyolmia with enamel defects. In the first family, the older brother had oligodontia and enamel hypoplasia; the younger brother had widely spaced permanent teeth, enamel hypoplasia, agenesis of both inferior second premolars and retention of their deciduous. In the second family, the patient had retarded eruption of permanent teeth, amelogenesis imperfecta, and taurodontic pulp chambers.

Inheritance

Bertola et al. (2009) suggested autosomal recessive inheritance of this disorder because of consanguinity and a negative family history for any bone or dental abnormalities in their families.

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Short stature

HEAD AND NECK: [Teeth]; Oligodontia; Amelogenesis imperfecta

SKELETAL: Delayed bone age; [Spine]; Platyspondyly; Thick, short pedicles; Narrow intervertebral spaces; Posterior scalloping; Herniated intervertebral nuclei; Narrow interpedicular space


Retrieved: 27-07-2015
Source: Orphanet (original)
Associated genes: gpc6, cd44



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

Brachyolmia type 1, Toledo type is an autosomal recessive form of brachyolmia (see this term), a group of rare genetic skeletal disorders, and is characterized by short stature, short trunk, and platyspondyly, as well as corneal opacities. Last update: January 2014


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

Description

Seller et al. (1996) described a sporadic case of lethal chondrodysplasia in a male fetus born of first-cousin Caucasian parents. The fetus manifested an absence of ossification of the skull vault and vertebral bodies in the cervical and thoracic regions, platyspondyly in the lumbar region, and short angulated ulnae, radii, femora, tibiae, and fibulae. The fetus also presented sclerosis of scapulae and iliac bones, and humeri with mixed sclerosis affecting the metaphyses and with lysis affecting predominantly the diaphyses. Seller et al. (1996) suggested that this fetus represents a 'new' autosomal recessive form of lethal chondrodysplasia.

Symptoms

Skel: Lethal chondrodysplasia

Limbs: Short angulated ulnae, radii, femora, tibiae, and fibulae

Radiology: Absent ossification of skull vault; Absent ossification of cervical and thoracic vertebral bodies; Lumbar platyspondyly; Sclerosis of scapulae and iliac bones; Mixed sclerosis of humeral metaphyses; Humeral diaphyseal lysis

Inheritance: Autosomal recessive


Retrieved: 27-07-2015
Source: Orphanet (original)
Associated genes: trpv4, papss2

Brachyolmia is a rare, clinically and genetically heterogeneous group of bone disorders characterized by short trunk, mild short stature, scoliosis and generalized platyspondyly without significant abnormalities in the long bones. The prevalence of brachyolmia is not known, but the disorder is probably under-recognized. Fewer than 100 cases have been reported to date. Cases have been reported in various ethnic groups. However, most cases with the Hobaek/Toledo type reported so far were of Turkish origin. Four types of brachyolmia have been described: autosomal recessive brachyolmia, Hobaek/Toledo type, autosomal recessive brachyolmia-amelogenesis imperfecta syndrome, autosomal dominant brachyolmia, and autosomal recessive brachyolmia, Maroteaux type (see these terms). The age of onset is generally in childhood with short stature becoming more evident with age. The clinical manifestations are generally mild to moderate, with minor physical functional repercussions. Some patients report non-specific back pain. The disorder is not associated with intellectual disability. AR brachyolmia, Hobaek/Toledo type is characterized by short-trunked short stature with platyspondyly and scoliosis. Corneal opacities and precocious calcification of costal cartilage occur in rare cases. In AR brachyolmia-amelogenesis imperfecta syndrome, short-trunked short stature is associated with platyspondyly and enamel abnormalities. AD brachyolmia is a more severe form with significant short-trunked short stature, platyspondyly and kyphoscoliosis. Lastly, presumably autosomal recessive brachyolmia, Maroteaux type is a vague entity that has not been well characterized but may involve short trunk/short stature, generalized platyspondyly and rounding vertebral bodies. Mutations in the PAPSS2 gene (10q24) have been found in patients with AR brachyolmia, Hobaek/Toledo type, and in the TRPV4 gene (12q24.1) in patients with AD brachyolmia. Precise pathogenesis is not well understood. Clinica...


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

Spondyloepiphyseal dysplasia tarda, Kohn type is characterized by short trunk dwarfism, progressive involvement of the spine and epiphyses and mild-to-moderate intellectual deficit. The syndrome has been described in three daughters born to healthy consanguineous parents. The skeletal disorder usually manifests in late childhood. Typical radiographical features include platyspondyly, abnormal lumbar vertebrae and degenerative large joint changes. Autosomal recessive transmission has been suggested. Last update: September 2009


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

Cardiomyopathy - cataract - hip spine disease describes the extremely rare triad of dilated cardiomyopathy, premature cataract, and articular disease of the hips and spine characterized by hip joint degeneration, irregular intervertebral disks, and platyspondyly. The ocular abnormalities are often the first symptoms to arise. There have been no further descriptions in the literature since 1985. Last update: January 2014


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

Clinical features

Lizcano-Gil et al. (1995) reported a family in which 5 members in 3 generations had camptodactyly (see 114200) in association with flattened cervical vertebral bodies and scoliosis. They suggested that the inheritance was autosomal dominant; however, the 3 affected females in the third generation were the products of a consanguineous marriage. The possibility of earlier consanguinity makes autosomal recessive inheritance with pseudodominance a possibility.

Symptoms

Limbs: Camptodactyly. Flexion contractures of proximal interphalangeal joints.

Spine: Scoliosis.

Radiology: Flattened cervical vertebral bodies.

Inheritance: Autosomal dominant vs. autosomal recessive with pseudodominance.


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

Clinical features

Ehara et al. (1997) presented a previously undescribed, probably autosomal recessive skeletal dysplasia characterized by mild platyspondyly, small thorax with cupping of the anterior ends of the ribs, irregular proximal femoral metaphyses, and lacy appearance of the iliac wings. The 3 patients were a Korean brother and sister and an unrelated Japanese child. Retinitis pigmentosa and optic atrophy were associated findings. The lacy appearance of the iliac crest is a feature also of Dyggve-Melchior-Claussen syndrome (223800), but Ehara et al. (1997) pointed out that the severe epiphyseal dysplasia of the proximal femurs and marked platyspondyly with particular double-hump appearance of the vertebral bodies seen in DMC syndrome were not present in their patients. Other rare forms of SMD could be excluded, they thought. The parents in neither case were consanguineous.

Isidor et al. (2010) reported 2 unrelated boys with short stature, femoral metaphyseal abnormalities, platyspondyly, and retinitis pigmentosa. The first boy, born of consanguineous parents, was evaluated at 7.5 years of age for short stature and found to have frontal bossing, a narrow bell-shaped thorax with prominent sternum, and rhizomelic shortening of the limbs. Radiologic examination showed moderate platyspondyly with ovoid vertebral bodies and enlarged short ribs, irregular iliac crest, and very abnormal femoral metaphyses with short and enlarged femoral neck. Bone age was moderately delayed. By 14.8 years of age, he had developed photophobia; ophthalmoscopy showed bilateral pale papillae, normal maculae, and diffuse atrophy of the pigmentary epithelium. Goldman visual fields were normal, whereas electroretinography (ERG) showed a 50% decrease in scotopic white and red waves. Cerebral MRI showed slight bilateral optic nerve atrophy. The other boy, born of healthy nonconsanguineous parents, was evaluated at 6.5 years of age for growth failure and noted to have delayed bone age, telecanthus and hypertelorism with antimongoloid palpebral fissures, slight eversion of the inferior eyelids, and short nose with anteverted nares. The thorax was very narrow with a bell-shaped thoracic cage, and he had rhizomelic shortening of the limbs; radiography showed spondylometaphyseal dysplasia, predominating in the pelvis and femoral neck, with lacy iliac wings. Ophthalmologic examination revealed bila...

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Short stature

HEAD AND NECK: [Eyes]; Retinitis pigmentosa; Optic atrophy; Nystagmus

RESPIRATORY: [Lung]; Pneumonia, recurrent

CHEST: [External features]; Small chest; [Ribs, sternum, clavicles, and scapulae]; Anterior cupping of ribs; Widened anterior ribs

SKELETAL: Spondylometaphyseal dysplasia; [Spine]; Mild platyspondyly; [Pelvis]; Lacy iliac wings; Narrow sacrosciatic notch; Irregular proximal femoral metaphyses; Short femoral necks; Coxa vara


Retrieved: 27-07-2015
Source: Orphanet (original)
Associated genes: pcyt1a

This syndrome is characterised by the association of spondylometaphyseal dysplasia (marked by platyspondyly, shortening of the tubular bones and progressive metaphyseal irregularity and cupping), with postnatal growth retardation and progressive visual impairment due to cone-rod dystrophy. So far, it has been described in eight individuals. Transmission appears to be autosomal recessive. Last update: March 2007


Retrieved: 27-07-2015
Source: OMIM (original)
Associated genes: atp7a, lox, dnah8

Description

A number sign (#) is used with this entry because occipital horn syndrome (OHS) is caused by mutation in the gene encoding Cu(2+)-transporting ATPase, alpha polypeptide (ATP7A; 300011). Menkes syndrome (309400) is caused by mutation in the same gene.Occipital horn syndrome is a rare connective tissue disorder characterized by hyperelastic and bruisable skin, hernias, bladder diverticula, hyperextensible joints, varicosities, and multiple skeletal abnormalities. The disorder is sometimes accompanied by mild neurologic impairment, and bony abnormalities of the occiput are a common feature, giving rise to the name (summary by Das et al., 1995).

Clinical features

Lazoff et al. (1975) described an unusual syndrome in an 11-year-old male and 2 maternal uncles. Bony 'horns,' symmetrically situated on each side of the foramen magnum and pointing caudad, were demonstrable radiographically. A lifelong history of frequent loose stools, obstructive uropathy requiring in 1 uncle ileal loop diversion, and mild mental retardation were other features. Some suspicion that a relative through the maternal grandfather had the same condition (which could not be confirmed because of lack of cooperation) meant that autosomal dominant inheritance with reduced penetrance could not be excluded.

Byers et al. (1976) found deficiency of lysyl oxidase in affected males in a family with apparent X-...

Symptoms

INHERITANCE: X-linked recessive

HEAD AND NECK: [Head]; Persistent, open anterior fontanel; [Face]; Long, thin face; High forehead; Long philtrum; [Nose]; Hooked nose; [Mouth]; High-arched palate; [Neck]; Long neck

CARDIOVASCULAR: [Vascular]; Orthostatic hypotension; Elongated, tortuous carotid arteries; Intracranial arterial narrowing

CHEST: [External features]; Narrow shoulders; Narrow chest; [Ribs, sternum, clavicles, and scapulae]; Short, broad clavicles; Pectus excavatum; Pectus carinatum; Short, broad ribs

ABDOMEN: [Gastrointestinal]; Chronic diarrhea; Hiatal hernia

GENITOURINARY: [Kidneys]; Hydronephrosis; [Ureters]; Ureteral obstruction; [Bladder]; Bladder diverticula; Bladder rupture

SKELETAL: Joint laxity; Osteoporosis; [Skull]; Occipital horn exostoses; [Spine]; Kyphosis; Mild platyspondyly; [Pelvis]; Coxa valga; Pelvic exostoses; [Limbs]; Short humeri; Genu valgum; Limited elbow extension; Limited knee extension; [Hands]; Capitate-hamate fusion; [Feet]; Pes planus

SKIN, NAILS, HAIR: [Skin]; Soft skin; Mildly extensible skin; Loose, redundant skin; Easy bruisability; [Hair]; Coarse hair

NEUROLOGIC: [Central nervous system]; Low-normal IQ

NEOPLASIA: Bladder carcinoma

LABORATORY ABNORMALITIES: Decreased serum copper; Decreased ceruloplasmin

MOLECULAR BASIS: Caused by mutation in the ATPase, Cu++ transporting, alpha polypeptide gene (ATP7A, 300011.0002)


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

Pseudodiastrophic dysplasia is characterized by rhizomelic shortening of the limbs and severe clubfoot deformity, in association with elbow and proximal interphalangeal joint dislocations, platyspondyly, and scoliosis. It has been described in about 10 patients. An autosomal recessive inheritance has been suggested. Pseudodiastrophic dysplasia differs from diastrophic dysplasia (see this term) on the basis of clinical, radiographic, and histopathologic findings. Clubfoot can be treated by surgical therapy, and neonatal contractures and scoliosis can be relieved by physical therapy. Several of the reported patients died in the neonatal period or during infancy. Last update: January 2007


Retrieved: 27-07-2015
Source: WIKIPEDIA (original)
Associated genes: papss2
Spondyloepimetaphyseal dysplasia, Pakistani type is a form of spondyloepimetaphyseal dysplasia involving PAPSS2 (also known as "ATPSK2"). The condition is rare.

Genetics

This condition is inherited in an autosomal recessive fashion. It is due to mutations in the Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 (PAPSS2) gene which is located on the long arm of chromosome 10 (10q22-q24).

Clinical features

This condition is a skeletal dysplasia characterized by short stature, mild brachydactyly, kyphoscoliosis, abnormal gait, enlarged knee joints, precocious osteoarthropathy, platyspondyly, delayed epiphyseal ossification, mild metaphyseal abnormalities, short stature and short and bowed legs. Intelligence is normal. Some patients may manifest premature pubarche and hyperandrogenism. Other features that may form part of the syndrome include precocious costal calcification, small iliac bones, short femoral necks, coxa vara, short halluces and fused vertebral bodies.

Radiology

Radiographic features include delayed epiphyseal ossification at the hips and knees, platyspondyly with irregular end plates and narrowed joint spaces, diffuse early osteoarthritic changes (in the spine and hands), mild brachydactyly and mild metaphyseal abnormalities which predominantly involve the hips and knees.

History

This condition was first described in a large eight generation consanguineous Pakistani family. The causative mutation was identified in 1998.


Retrieved: 27-07-2015
Source: Orphanet (original)
Associated genes: trpv4

Autosomal dominant brachyolmia is a relatively severe form of brachyolmia (see this term), a group of rare genetic skeletal disorders, characterized by short-trunked short stature, platyspondyly and kyphoscoliosis. Degenerative joint disease (osteoarthropathy) in the spine, large joints and interphalangeal joints becomes manifest in adulthood. The precise prevalence of this form of brachyolmia is not known. About 30 cases have been reported. Patients with Brachyolmia type 3 generally have a normal birth weight and length. Affected individuals present with moderately short trunk/short stature and mildly short limbs in childhood. Kyphoscoliosis is common and sometimes severe. Adult patients develop degenerative joint disease in the spine, large joints and small joints of the hands and feet, which may cause significant musculoskeletal morbidity, such as chronic pain in the extremities and spine, and paresthesia. Final adult height is reported to be 155-168 cm (males) and 136-150 cm (females). The radiographic features include severe platyspondyly particularly in the cervical spine, elongated vertebral bodies (overfaced pedicles), broad ilia, and mild metaphyseal irregularity in the proximal femora. Carpal ossification may be mildly delayed, and mild brachydactyly may exist. Heterozygous mutations in the TRPV4 gene (12q24.11) are responsible for autosomal dominant brachyolmia. TRPV4 mutations are associated with other skeletal dysplasias, including lethal and nonlethal metatropic dysplasia, spondyloepiphyseal dysplasia Maroteaux type, and spondylometaphyseal dysplasia Kozlowski type (see these terms). Autosomal dominant brachyolmia falls into the mildest end of the TRPV4-associated skeletal dysplasia group. TRPV4 encodes a Ca-permeable, non-selective cation channel that participates in the regulation of osmotic sensitivity and mechanosensitivity. It remains to be explained how dysregulation of the cation channel causes the skeletal abnormalities. Genetic counse...