Cataract, and Hirsutism

Congenital generalized lipodystrophy, also known as Berardinelli-Seip syndrome, is an autosomal recessive disorder characterized by marked paucity of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis, and early onset of diabetes (Garg, 2004).For a general description and a discussion of genetic heterogeneity of congenital generalized lipodystrophy, see CGL1 (OMIM ).See also partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome (LCCNS ), which is associated with heterozygous mutation in the CAV1 gene.

LIPODYSTROPHY, CONGENITAL GENERALIZED, TYPE 3; CGL3 Is also known as berardinelli-seip congenital lipodystrophy, type 3|bscl3|lipodystrophy, berardinelli-seip congenital, type 3

• Short stature
• Cataract
• Diabetes mellitus
• Hepatosplenomegaly
• Congenital cataract

SOURCES: OMIM MESH MENDELIAN

The erythrokeratodermias are a clinically variable and genetically heterogeneous group of inherited disorders characterized by widespread erythematous plaques, stationary or migratory, associated with nonmigratory hyperkeratoses (summary by Ishida-Yamamoto et al., 1997). The condition is usually present at birth or occurs during the first year but may begin later in childhood or even in early adulthood. Lesions preferentially affect the face, buttocks, and extensor surfaces of the limbs. Palmoplantar keratoderma occurs in about half the cases, but hair, nails, and teeth are not affected (summary by Macfarlane et al., 1991). Genetic Heterogeneity of Erythrokeratodermia Variabilis et ProgressivaSee EKVP2 (OMIM ), caused by mutation in the GJB4 gene (OMIM ); EKVP3 (OMIM ), caused by mutation in the GJA1 gene (OMIM ); EKVP4 (OMIM ), caused by mutation in the KDSR gene (OMIM ); and EKVP5 (OMIM ), caused by mutation in the KRT83 gene (OMIM ).

ERYTHROKERATODERMIA VARIABILIS Is also known as psek|erythrokeratodermia variabilis et progressiva|ekvp|ekv|erythrokeratodermia variabilis, mendes da costa type|erythrokeratodermia figurata, congenital familial, in plaques|erythrokeratodermia, progressive symmetric|erythrokeratodermia variabilis with e

• Intellectual disability
• Short stature
• Hearing impairment
• Microcephaly
• Cataract

SOURCES: OMIM ORPHANET MENDELIAN

Curry-Jones syndrome is a form of syndromic craniosynostosis characterized by unilateral coronal craniosynostosis or multiple suture synostosis associated with complete or partial agenesis of the corpus callosum, preaxial polysyndactyly and syndactyly of hands and/or feet, along with anomalies of the skin (characteristic pearly white areas that become scarred and atrophic, abnormal hair growth around the eyes and/or cheeks, and on the limbs), eyes (iris colobomas, microphthalmia,) and intestine (congenital short gut, malrotation, dysmotility, chronic constipation, bleeding and myofibromas). Developmental delay and variable degrees of intellectual disability may also be observed. Multiple intra-abdominal smooth muscle hamartomas, trichoblastoma of the skin, occipital meningoceles and development of desmoplastic medulloblastoma have been reported.

CURRY-JONES SYNDROME Is also known as corpus callosum agenesis-polysyndactyly syndrome|craniofacial malformations, asymmetric, with polysyndactyly and abnormal skin and gut development

• Intellectual disability
• Global developmental delay
• Microcephaly
• Hypertelorism
• Nystagmus

SOURCES: OMIM ORPHANET MESH MENDELIAN

Cushing disease (CD) is the most common cause of endogenous Cushing syndrome (CS; see this term) and is due to pituitary chronic over-secretion of ACTH by a pituitary corticotroph adenoma.

CUSHING DISEASE Is also known as corticotroph pituitary adenoma|pituitary-dependent cushing syndrome|pituitary corticotroph micro-adenoma

• Failure to thrive
• Cataract
• Visual impairment
• Hypertension
• Fatigue

SOURCES: ORPHANET MENDELIAN

Micro syndrome is an autosomal recessive disorder caracterised by ocular and neurodevelopmental defects and by microgenitalia. It presents with severe intellectual disability, microcephaly, congenital cataract, microcornea, microphthalmia, agenesis/hypoplasia of the corpus callosum, and hypogenitalism.

MICRO SYNDROME Is also known as warbm|warburg micro syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: OMIM ORPHANET MENDELIAN

Zankl et al. (2007) defined what they considered to be a continuous clinical spectrum involving Torg syndrome, Winchester syndrome (OMIM ), and NAO syndrome. Torg syndrome is characterized by the presence of multiple, painless, subcutaneous nodules and mild to moderate osteoporosis and osteolysis that is usually limited to the hands and feet. Radiographically, the osteolysis is accompanied by a characteristic widening of the metacarpal and metatarsal bones. Winchester syndrome presents with severe osteolysis in the hands and feet and generalized osteoporosis and bone thinning, similar to NAO, but subcutaneous nodules are characteristically absent. Various additional features including coarse face, corneal opacities, gum hypertrophy, and EKG changes have been reported. NAO syndrome, which has only been described in patients from Saudi Arabia, is generally more severe, with multiple prominent and painful subcutaneous nodules, massive osteolysis in the hands and feet, and generalized osteoporosis. Coarse face and body hirsutism are additional features.

MULTICENTRIC OSTEOLYSIS, NODULOSIS, AND ARTHROPATHY; MONA Is also known as osteolysis, hereditary multicentric|torg syndrome|al-aqeel sewairi syndrome|nodulosis-arthropathy-osteolysis syndrome|torg-winchester syndrome, formerly|nao syndrome

• Short stature
• Scoliosis
• Hypertelorism
• Micrognathia
• Cataract

SOURCES: ORPHANET OMIM MENDELIAN

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is an endogenous form of adrenal Cushing syndrome characterized by multiple bilateral adrenocortical nodules that cause a striking enlargement of the adrenal glands. Although some familial cases have been reported, the vast majority of AIMAH cases are sporadic. Patients typically present in the fifth and sixth decades of life, approximately 10 years later than most patients with other causes of Cushing syndrome (Swain et al., 1998; Christopoulos et al., 2005).Approximately 10 to 15% of adrenal Cushing syndrome is due to primary bilateral ACTH-independent adrenocortical pathology. The 2 main subtypes are AIMAH and primary pigmented nodular adrenocortical disease (PPNAD, see {610489}), which is often a component of the Carney complex (OMIM ) and associated with mutations in the PRKAR1A gene (OMIM ) on chromosome 17q23-q24. AIMAH is rare, representing less than 1% of endogenous causes of Cushing syndrome (Swain et al., 1998; Christopoulos et al., 2005).See also ACTH-independent Cushing syndrome (OMIM ) due to somatic mutation in the PRKACA gene (OMIM ).Cushing 'disease' (OMIM ) is an ACTH-dependent disorder caused in most cases by pituitary adenomas that secrete excessive ACTH. Genetic Heterogeneity of ACTH-Independent Macronodular Adrenal HyperplasiaAIMAH2 (OMIM ) is caused by germline mutation of 1 allele of the ARMC5 gene (OMIM ) coupled with a somatic mutation in the other allele.

ACTH-INDEPENDENT MACRONODULAR ADRENAL HYPERPLASIA; AIMAH1 Is also known as acth-independent macronodular adrenocortical hyperplasia|cushing syndrome, adrenal, due to aimah|corticotropin-independent macronodular adrenal hyperplasia|adrenocorticotropic hormone-independent macronodular adrenal hyperplasia

• Neoplasm
• Failure to thrive
• Muscle weakness
• Cataract
• Visual impairment

SOURCES: OMIM MESH MENDELIAN

Cerebrooculofacioskeletal syndrome is an autosomal recessive progressive neurodegenerative disorder characterized by microcephaly, congenital cataracts, severe mental retardation, facial dysmorphism, and arthrogryposis (summary by Jaakkola et al., 2010). Genetic Heterogeneity of Cerebrooculofacioskeletal SyndromeSee also COFS2 (OMIM ), caused by mutation in the ERCC2 gene (OMIM ); COFS3 (OMIM ), caused by mutation in the ERCC5 gene (OMIM ); and COFS4 (OMIM ), caused by mutation in the ERCC1 gene (OMIM ).

CEREBROOCULOFACIOSKELETAL SYNDROME 1; COFS1 Is also known as cofs syndrome|cofs|pena-shokeir syndrome, type ii

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment

SOURCES: ORPHANET OMIM MENDELIAN

ADNP syndrome is a rare, syndromic intellectual disability characterized by intellectual disability of various severity, hypotonia, global developmental delay, severely delayed speech, behavioral problems, pain insensitivity, sleep problems, seizures, structural brain anomalies, dysmorphic features, visual problems and autism.

ADNP SYNDROME Is also known as adnp-related syndromic intellectual disability-autism spectrum disorder|hvdas|mental retardation, autosomal dominant 28|mrd28|helsmoortel-van der aa syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: ORPHANET OMIM MENDELIAN

Bardet-Biedl syndrome is an autosomal recessive and genetically heterogeneous ciliopathy characterized by retinitis pigmentosa, obesity, kidney dysfunction, polydactyly, behavioral dysfunction, and hypogonadism (summary by Beales et al., 1999). Eight proteins implicated in the disorder assemble to form the BBSome, a stable complex involved in signaling receptor trafficking to and from cilia (summary by Scheidecker et al., 2014). Genetic Heterogeneity of Bardet-Biedl SyndromeBBS1 is caused by mutation in a gene on chromosome 11q13 (OMIM ); BBS2 (OMIM ), by mutation in a gene on 16q13 (OMIM ); BBS3 (OMIM ), by mutation in the ARL6 gene on 3q11 (OMIM ); BBS4 (OMIM ), by mutation in a gene on 15q22 (OMIM ); BBS5 (OMIM ), by mutation in a gene on 2q31 (OMIM ); BBS6 (OMIM ), by the MKKS gene on 20p12 (OMIM ), mutations in which also cause McKusick-Kaufman syndrome (OMIM ); BBS7 (OMIM ), by mutation in a gene on 4q27 (OMIM ); BBS8 (OMIM ), by mutation in the TTC8 gene on 14q32 (OMIM ); BBS9 (OMIM ), by mutation in a gene on 7p14 (OMIM ); BBS10 (OMIM ), by mutation in a gene on 12q (OMIM ); BBS11 (OMIM ), by mutation in the TRIM32 gene on 9q33 (OMIM ); BBS12 (OMIM ), by mutation in a gene on 4q27 (OMIM ); BBS13 (OMIM ), by mutation in the MKS1 gene (OMIM ) on 17q23, mutations in which also cause Meckel syndrome-1 (OMIM ); BBS14 (OMIM ), by mutation in the CEP290 gene (OMIM ) on 12q21, mutations in which also cause Meckel syndrome-4 (OMIM ) and several other disorders; BBS15 (OMIM ), by mutation in the C2ORF86 gene (OMIM ), which encodes a homolog of the Drosophila planar cell polarity gene 'fritz,' on 2p15; BBS16 (OMIM ), by mutation in the SDCCAG8 gene (OMIM ) on 1q43, mutations in which also cause Senior-Loken syndrome-7 (OMIM ); BBS17 (OMIM ), by mutation in the LZTFL1 gene (OMIM ) on 3p21; BBS18 (OMIM ), by mutation in the BBIP1 gene (OMIM ) on 10q25; BBS19 (OMIM ), by mutation in the IFT27 gene (OMIM ) on 22q12; BBS20 (OMIM ), by mutation in the IFT74 gene (OMIM ) on 9p21; and BBS21 (OMIM ), by mutation in the C8ORF37 gene (OMIM ).The CCDC28B gene (OMIM ) modifies the expression of BBS phenotypes in patients who have mutations in other genes. Mutations in MKS1, MKS3 (TMEM67 ), and C2ORF86 also modify the expression of BBS phenotypes in patients who have mutations in other genes.Although BBS had originally been thought to be a recessive disorder, Katsanis et al. (2001) demonstrated that clinical manifestation of some forms of Bardet-Biedl syndrome requires recessive mutations in 1 of the 6 loci plus an additional mutation in a second locus. While Katsanis et al. (2001) called this 'triallelic inheritance,' Burghes et al. (2001) suggested the term 'recessive inheritance with a modifier of penetrance.' Mykytyn et al. (2002) found no evidence of involvement of the common BBS1 mutation in triallelic inheritance. However, Fan et al. (2004) found heterozygosity in a mutation of the BBS3 gene ({608845.0002}) as an apparent modifier of the expression of homozygosity of the met390-to-arg mutation in the BBS1 gene ({209901.0001}).Allelic disorders include nonsyndromic forms of retinitis pigmentosa: RP51 (OMIM ), caused by TTC8 mutation, and RP55 (OMIM ), caused by ARL6 mutation.

• Intellectual disability
• Global developmental delay
• Hearing impairment
• Ataxia
• Nystagmus

SOURCES: OMIM MENDELIAN