Beighton (1981) reported a kindred in which 20 members in at least 3 generations had opalescent teeth, blue sclerae, wormian bones, and normal height. In the 6 affected individuals who had skeletal surveys, moderate generalized osteoporosis was noted; the older individuals had mild flattening and biconcavity of the vertebral bodies. Only 1 affected individual, an adolescent male, had pronounced platybasia and had sustained 10 femoral fractures on mild trauma. Only the proband had hearing loss. No individuals had joint hyperextensibility. It is not known whether the syndrome is the same as OI type I (166200).
A number sign (#) is used with this entry because OI type I (OI1) is caused by heterozygous mutation in the COL1A1 gene (120150) or the COL1A2 gene (120160). Description Osteogenesis imperfecta type I is a dominantly inherited, generalized connective tissue disorder characterized mainly by bone fragility and blue sclerae. In most cases, 'functional null' alleles of COL1A1 on chromosome 17 or COL1A2 on chromosome 7 lead to reduced amounts of normal collagen I. Clinical Features Osteogenesis imperfecta (see Byers, 1993) is characterized chiefly by multiple bone fractures, usually resulting from minimal trauma. Affected individuals have blue sclerae, normal teeth, and normal or near-normal stature (for growth curves, see Vetter et al., 1992).
Osteogenesis imperfecta (OI) comprises a heterogeneous group of genetic disorders characterized by increased bone fragility, low bone mass, and susceptibility to bone fractures with variable severity. Epidemiology Prevalence is estimated at between 1/10,000 and 1/20,000. Clinical description Age at diagnosis depends on the severity of the disease. Five clinically distinct types of OI have been identified. The most clinically relevant characteristic of all types of OI is bone fragility, which manifests as multiple spontaneous fractures. Osteogenesis imperfecta type II is lethal, type III is severe, types IV and V are moderate, and type I is mild (see these terms).
Osteogenesis imperfecta (OI) is a group of genetic disorders that mainly affect the bones. The term "osteogenesis imperfecta" means imperfect bone formation. People with this condition have bones that break easily, often from mild trauma or with no apparent cause. Multiple fractures are common, and in severe cases, can occur even before birth. Milder cases may involve only a few fractures over a person's lifetime. There are at least eight recognized forms of osteogenesis imperfecta, designated type I through type VIII.
Osteogenesis imperfecta (OI) is a group of genetic disorders that mainly affect the bones. Osteogenesis imperfecta type 1 is the mildest form of OI and is characterized by bone fractures during childhood and adolescence that often result from minor trauma. Fractures occur less frequently in adulthood. People with mild forms of the condition typically have a blue or grey tint to the part of the eye that is usually white (the sclera), and may develop hearing loss in adulthood. Affected individuals are usually of normal or near normal height. Most of the mutations that cause osteogenesis imperfecta type 1 occur in the COL1A1 gene. These genetic changes reduce the amount of type I collagen produced in the body, which causes bones to be brittle and to fracture easily.
Osteogenesis imperfecta type I is a mild type of osteogenesis imperfecta (OI; see this term), a genetic disorder characterized by increased bone fragility, low bone mass and susceptibility to bone fractures. Epidemiology The overall prevalence of OI is estimated at between 1/10,000 and 1/20,000 but the prevalence of type I is unknown. Clinical description OI type I is nondeforming with normal height or mild short stature, blue sclera, and no dentinogenesis imperfecta (DI; see this term). Etiology OI type I is caused by mutations in the COL1A1 and COL1A2 genes (17q21.31-q22 and 7q22.1 respectively). Genetic counseling Transmission is autosomal dominant.
Silicosis is a respiratory disease caused by breathing in (inhaling) silica dust. There are three types of silicosis: Simple chronic silicosis, the most common type of silicosis, results from long-term exposure (usually more than 20 years) to low amounts of silica dust. Simple chronic silicosis may cause people to have difficulty breathing. Accelerated silicosis occurs after 5 to 15 years of exposure of higher levels of silica. Swelling of the lungs and other symptoms occur faster in this type of silicosis than in the simple chronic form.
A rare, aggressive, malignant, neoplastic disease characterized by a usually ill-defined, solid, multilobulated mass, frequently having necrosis, located on any site of the body (except the central nervous system), composed of small, round, poorly differentiated cells, with or without Homer-Wright rosettes, showing varying degrees of neuroectodermal differentiation. Manifestations are variable depending on location, with osteolytic destruction being common when arising from bone.
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A number sign (#) is used with this entry because of evidence that hereditary sensory neuropathy type IF (HSN1F) is caused by heterozygous mutation in the ATL3 gene (609369) on chromosome 11q13. Description Hereditary sensory neuropathy type IF is an autosomal dominant sensory neuropathy affecting the lower limbs. Distal sensory impairment becomes apparent during the second or third decade of life, resulting in painless ulceration of the feet with poor healing, which can progress to osteomyelitis, bone destruction, and amputation. There is no autonomic involvement, spasticity, or cognitive impairment (summary by Kornak et al., 2014). For a discussion of genetic heterogeneity of HSN, see HSAN1A (162400).
Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. Epidemiology The exact prevalence is unknown, but is estimated as very low. Clinical description Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is a reduction of sensation sense, mainly distributed around the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic.
Hereditary sensory neuropathy type 1 (HSN1) is a neurological condition characterized by nerve abnormalities in the legs and feet. Many people with this condition have tingling, weakness, and a reduced ability to feel pain and sense hot and cold. Some affected people do not lose sensation, but instead feel shooting pains in their legs and feet. As HSN1 progresses, sensory problems can affect the hands, arms, shoulders, and abdomen. In rare cases, people with this condition develop sensorineural hearing loss.
A number sign (#) is used with this entry because hereditary sensory and autonomic neuropathy type IC (HSAN1C) is caused by heterozygous mutation in the SPTLC2 gene (605713) gene on chromosome 14q24. For a discussion of genetic heterogeneity of HSAN, see HSAN1A (162400). Clinical Features Rotthier et al. (2010) reported 4 unrelated probands with hereditary sensory neuropathy. Three probands had adult onset (ages 38, 37, and 52 years) of distal sensory loss. The presenting symptoms in these patients included loss of touch and vibration in the feet, dysesthesia and severe panmodal sensory loss in the upper and lower limbs, and distal lower limb sensory loss with ulceration and osteomyelitis necessitating amputation of the right great toe.
Summary Clinical characteristics. SPTLC1-related hereditary sensory neuropathy (HSN) is an axonal form of hereditary motor and sensory neuropathy distinguished by prominent early sensory loss and later positive sensory phenomena including dysesthesia and characteristic "lightning" or "shooting" pains. Loss of sensation can lead to painless injuries, which, if unrecognized, result in slow wound healing and subsequent osteomyelitis requiring distal amputations. Motor involvement is present in all advanced cases and can be severe. After age 20 years, the distal wasting and weakness may involve proximal muscles, possibly leading to wheelchair dependency by the seventh or eighth decade. Sensorineural hearing loss is variable. Diagnosis/testing. The diagnosis of SPTLC1-related HSN is established in a proband with characteristic clinical features and identification of a heterozygous pathogenic variant in SPTLC1 on molecular genetic testing.
A number sign (#) is used with this entry because hereditary sensory neuropathy type IA (HSAN1A) is caused by heterozygous mutation in the SPTLC1 gene (605712) on chromosome 9q22. Description The hereditary sensory and autonomic neuropathies (HSAN), which are also referred to as hereditary sensory neuropathies (HSN) in the absence of significant autonomic features, are a genetically and clinically heterogeneous group of disorders associated with sensory dysfunction. HSAN1 is a dominantly inherited sensorimotor axonal neuropathy with onset in the first or second decades of life. Genetic Heterogeneity of Hereditary Sensory and Autonomic Neuropathy See also HSAN1C (613640), caused by mutation in the SPTLC2 gene (605713) on 14q24; HSN1D (613708), caused by mutation in the ATL1 gene (606439) on 14q; HSN1E (614116), caused by mutation in the DNMT1 gene (126375) on 19p13; HSN1F (615632), caused by mutation in the ATL3 gene (609369) on 11q13; HSAN2A (201300), caused by mutation in the HSN2 isoform of the WNK1 gene (605232) on 12p13; HSAN2B (613115), caused by mutation in the FAM134B gene (613114) on 5p15; HSN2C (614213), caused by mutation in the KIF1A gene (601255) on 2q37; HSAN2D (see 243000), caused by mutation in the SCN9A gene (603415) on 2q24; HSAN3 (223900), caused by mutation in the IKBKAP gene (603722) on 9q31; HSAN4 (256800), caused by mutation in the NTRK1 gene (191315) on 1q23; HSAN5 (608654), caused by mutation in the NGF gene (162030) on 1p13; HSAN6 (614653), caused by mutation in the DST gene (113810) on 6p; HSAN7 (615548), caused by mutation in the SCN11A gene (604385) on 3p22; and HSAN8 (616488), caused by mutation in the PRDM12 gene (616458) on chromosome 9q34. Adult-onset HSAN with anosmia (608720) is believed to be another distinct form of HSAN, and HSAN1B (608088) with cough and gastroesophageal reflux maps to chromosome 3p24-p22.
Hereditary sensory and autonomic neuropathy type IE (HSAN IE) is a disorder that affects the nervous system. It is characterized by three main features: hearing loss, a decline of intellectual function (dementia), and a worsening loss of sensation in the feet and legs (peripheral neuropathy). People with HSAN IE develop hearing loss that is caused by abnormalities in the inner ear (sensorineural hearing loss). The hearing loss, which affects both ears, gets worse over time and usually progresses to moderate or severe deafness between the ages of 20 and 35. Affected individuals experience dementia typically beginning in their thirties.
Hereditary sensory neuropathy type IA is a condition characterized by nerve abnormalities in the legs and feet (peripheral neuropathy). Many people with this condition experience prickling or tingling sensations (paresthesias), numbness, and a reduced ability to feel pain and sense hot and cold. Some affected individuals do not lose sensation, but instead feel shooting pains in their legs and feet. As the disorder progresses, the sensory abnormalities can affect the hands, arms, shoulders, joints, and abdomen. Affected individuals may also experience muscle wasting and weakness as they get older.
A number sign (#) is used with this entry because autosomal dominant hereditary sensory neuropathy type 1D (HSN1D) is caused by heterozygous mutation in the atlastin-1 gene (ATL1; 606439) on chromosome 14q. Description Autosomal dominant hereditary sensory neuropathy type 1D is characterized by adult onset of a distal axonal sensory neuropathy affecting all modalities, often associated with distal ulceration and amputation as well as hyporeflexia, although some patients may show features suggesting upper neuron involvement (summary by Guelly et al., 2011). For a discussion of genetic heterogeneity of HSAN, see HSAN1A (162400). Spastic paraplegia-3A (SPG3A; 182600) is an allelic disorder with a different phenotype. Clinical Features Guelly et al. (2011) reported a 4-generation family with hereditary sensory neuropathy inherited in an autosomal dominant pattern.
A number sign (#) is used with this entry because fragile X (FXS) is caused by mutation in the FMR1 gene (309550). The vast majority of cases are caused by a trinucleotide (CGG)n repeat expansion (309550.0004) of greater than 200 repeats. See also fragile X tremor/ataxia syndrome (FXTAS; 300623), which is caused by expanded FMR1 (CGG)n repeats that range in size from 55 to 200 repeats and are referred to as 'premutations.' Description Fragile X syndrome is characterized by moderate to severe mental retardation, macroorchidism, and distinct facial features, including long face, large ears, and prominent jaw. In most cases, the disorder is caused by the unstable expansion of a CGG repeat in the FMR1 gene and abnormal methylation, which results in suppression of FMR1 transcription and decreased protein levels in the brain (Devys et al., 1993).
Fragile X syndrome is a genetic condition involving changes in part of the X chromosome. This condition causes a range of developmental problems including learning disabilities and cognitive impairment. It is the most common form of inherited intellectual disability in males and a significant cause of intellectual disability in females. Other signs and symptoms may include symptoms of autism spectrum disorders, seizures, and characteristic physical features. Fragile X syndrome is caused by a change (mutation) in the FMR1 gene and is inherited in an X-linked dominant manner.
Fragile X syndrome is a genetic condition that causes a range of developmental problems including learning disabilities and cognitive impairment. Usually, males are more severely affected by this disorder than females. Affected individuals usually have delayed development of speech and language by age 2. Most males with fragile X syndrome have mild to moderate intellectual disability, while about one-third of affected females are intellectually disabled. Children with fragile X syndrome may also have anxiety and hyperactive behavior such as fidgeting or impulsive actions.
Fragile X syndrome (FXS) is a rare genetic disease associated with mild to severe intellectual deficit that may be associated with behavioral disorders and characteristic physical features. Epidemiology Prevalence is estimated at approximately 1/4000-1/5000 although the prevalence may vary, depending on where the screening is carried out in the world. Clinical description FXS presents with a variable clinical phenotype. In males, the disease presents during childhood with delayed developmental milestones. Intellectual deficit can be of variable severity and may include problems with working and short-term memory, executive function, language, mathematics and visuospatial abilities.
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Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism and is characterized by mild to severe mental disability in untreated patients. Epidemiology The prevalence of PKU shows considerable geographic variation. It is estimated to be 1/10,000 live births in Europe with a higher rate in some countries (Ireland, Italy). Prevalence is particularly high in Turkey: 1/4,000 live births. PKU is far rarer in the Finnish, African and Japanese populations. Clinical description In the absence of neonatal diagnosis, symptoms develop within a few months of birth, may be very mild to severe and include gradual developmental delay, stunted growth, microcephaly, seizures, tremors, eczema, vomiting, and musty odor.
Phenylketonuria (PKU) is a genetic metabolic disorder that increases the body's levels of phenylalanine. Phenylalanine is one of the building blocks (amino acids) of proteins. Humans cannot make phenyalanine, but it is a natural part of the foods we eat. However, people do not need all the phenyalanine they eat, so the body converts extra phenylalanine to another harmless amino acid, tyrosine. People with PKU cannot properly break down the extra phenylalanine to convert it to tyrosine.
Phenylketonuria (commonly known as PKU) is an inherited disorder that increases the levels of a substance called phenylalanine in the blood. Phenylalanine is a building block of proteins (an amino acid) that is obtained through the diet. It is found in all proteins and in some artificial sweeteners. If PKU is not treated, phenylalanine can build up to harmful levels in the body, causing intellectual disability and other serious health problems. The signs and symptoms of PKU vary from mild to severe. The most severe form of this disorder is known as classic PKU. Infants with classic PKU appear normal until they are a few months old.
(eds.). Gene Expression in Muscle. Plenum Press. pp. 3–5. ISBN 978-1-4684-4907-5 . ^ a b c d MedlinePlus Encyclopedia Duchenne muscular dystrophy ^ Online Mendelian Inheritance in Man (OMIM) Muscular Dystrophy, Duchenne Type; DMD -310200 ^ "Duchenne Muscular Dystrophy: Pathophysiological Implications of Mitochondrial Calcium Signaling and ROS Production". 2012-05-02.
Duchenne muscular dystrophy (DMD) is a neuromuscular disease characterized by rapidly progressive muscle weakness and wasting due to degeneration of skeletal, smooth and cardiac muscle. Epidemiology DMD primarily affects males with an estimated incidence of 1/3,300 male births. Females are usually asymptomatic but a small percentage of female carriers manifest milder forms of the disease (symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers; see this term). Clinical description Onset occurs in early childhood, and affected boys may show a delay in motor milestones or global developmental delay. Children with DMD generally never achieve the ability to run or jump.
Duchenne muscular dystrophy (DMD) is a progressive form of muscular dystrophy that occurs primarily in males, though in rare cases may affect females. DMD causes progressive weakness and loss (atrophy) of skeletal and heart muscles. Early signs of DMD may include delayed ability to sit, stand, or walk and difficulties learning to speak. Muscle weakness is usually noticeable by 3 or 4 years of age and begins in the hips, pelvic area, upper legs, and shoulders. The calves may be enlarged. Children with DMD may have an unusual walk and difficulty running, climbing stairs, and getting up from the floor.
A number sign (#) is used with this entry because Duchenne muscular dystrophy is caused by mutation in the gene encoding dystrophin (DMD; 300377). Description Dystrophin-associated muscular dystrophies range from the severe Duchenne muscular dystrophy (DMD) to the milder Becker muscular dystrophy (BMD; 300376). Mapping and molecular genetic studies indicate that both are the result of mutations in the huge gene that encodes dystrophin, also symbolized DMD. Approximately two-thirds of the mutations in both forms are deletions of one or many exons in the dystrophin gene. Although there is no clear correlation found between the extent of the deletion and the severity of the disorder, DMD deletions usually result in frameshift.