Ataxia, and Asthma

CHOREA, BENIGN HEREDITARY; BHC Is also known as hereditary progressive chorea without dementia|bch

• Ataxia
• Cognitive impairment
• Motor delay
• Dysarthria
• Gait disturbance

SOURCES: OMIM MENDELIAN

Brain-lung-thyroid syndrome is a rare disorder characterized by congenital hypothyroidism (CH), infant respiratory distress syndrome (IRDS) and benign hereditary chorea (BHC; see these terms).

BRAIN-LUNG-THYROID SYNDROME Is also known as choreoathetosis-hypothyroidism-neonatal respiratory distress syndrome|brain-lung-thyroid syndrome

• Global developmental delay
• Generalized hypotonia
• Ataxia
• Muscular hypotonia
• Motor delay

SOURCES: OMIM MESH ORPHANET MENDELIAN

PGM3-CDG is a rare congenital disorder of glycosylation caused by mutations in the PGM3 gene and characterized by neonatal to childhood onset of recurrent bacterial and viral infections, inflammatory skin diseases, atopic dermatitis and atopic diatheses, and marked serum IgE elevation. Early neurologic impairment is evident including developmental delay, intellectual disability, ataxia, dysarthria, sensorineural hearing loss, myoclonus and seizures.

PGM3-CDG Is also known as cid due to pgm3 deficiency|immunodeficiency with hyper ige and cognitive impairment|pgm3-related congenital disorder of glycosylation|combined immunodeficiency due to pgm3 deficiency|immunodeficiency-vasculitis-myoclonus syndrome|ivms

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

SOURCES: OMIM ORPHANET 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

Gamma-glutamyl transpeptidase deficiency is characterized by increased glutathione concentration in the plasma and urine.

GAMMA-GLUTAMYL TRANSPEPTIDASE DEFICIENCY Is also known as glutathionuria|gtg deficiency|ggt deficiency|gamma-glutamyltransferase deficiency|gamma-glutamyltranspeptidase deficiency

• Intellectual disability
• Seizures
• Hypertelorism
• Strabismus
• Low-set ears

SOURCES: OMIM ORPHANET MESH MENDELIAN

Mucopolysaccharidosis II is a rare X-linked recessive disorder caused by deficiency of the lysosomal enzyme iduronate sulfatase, leading to progressive accumulation of glycosaminoglucans in nearly all cell types, tissues, and organs. Patients with MPS II excrete excessive amounts of chondroitin sulfate B (dermatan sulfate) and heparitin sulfate (heparan sulfate) in the urine (McKusick, 1972; Wraith et al., 2008).

MUCOPOLYSACCHARIDOSIS, TYPE II; MPS2 Is also known as hunter syndrome|sulfoiduronate sulfatase deficiency|sids deficiency|mps ii|ids deficiency|iduronate 2-sulfatase deficiency

• Intellectual disability
• Seizures
• Global developmental delay
• Hearing impairment
• Ptosis

SOURCES: OMIM MENDELIAN

Maternal phenylketonuria (PKU) is a rare disorder of phenylalanine metabolism (see this term), an inborn error of amino acid metabolism, characterized by the development of microcephaly, growth retardation, congenital heart disease, facial dysmorphism and intellectual disability in nonphenylketonuric offspring of mothers with excess phenylalanine (Phe) concentrations.

MATERNAL PHENYLKETONURIA Is also known as phenylalanine hydroxylase deficiency|phenylketonuric embryopathy|maternal pku|pah deficiency|folling disease|maternal hyperphenylalaninemia|hyperphenylalaninemic embryopathy|oligophrenia phenylpyruvica

• Intellectual disability
• Seizures
• Global developmental delay
• Microcephaly
• Growth delay

SOURCES: ORPHANET OMIM MENDELIAN

Alström syndrome (AS) is a multisystemic disorder characterized by cone-rod dystrophy, hearing loss, obesity, insulin resistance and hyperinsulinemia, type 2 diabetes mellitus, dilated cardiomyopathy (DCM; see this term), and progressive hepatic and renal dysfunction.

ALSTRÖM SYNDROME Is also known as alss

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Hearing impairment

SOURCES: OMIM ORPHANET MESH MENDELIAN

Mitochondrial DNA depletion syndrome-4B is an autosomal recessive progressive multisystem disorder clinically characterized by chronic gastrointestinal dysmotility and pseudoobstruction, cachexia, progressive external ophthalmoplegia (PEO), axonal sensory ataxic neuropathy, and muscle weakness (van Goethem et al., 2003).For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (OMIM ).

MITOCHONDRIAL DNA DEPLETION SYNDROME 4B (MNGIE TYPE); MTDPS4B Is also known as mngie, polg-related|mitochondrial neurogastrointestinal encephalopathy syndrome, polg-related

• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia
• Hearing impairment

SOURCES: OMIM MENDELIAN

Myotonia permanens is a very rare, persistent and more severe form of potassium-aggravated myotonia (PAM, see this term).

• Intellectual disability
• Short stature
• Muscle weakness
• Epicanthus
• Gait disturbance

SOURCES: ORPHANET MENDELIAN