MedGen

Charcot-Marie-Tooth disease is a sensorineural peripheral polyneuropathy. Affecting approximately 1 in 2,500 individuals, Charcot-Marie-Tooth disease is the most common inherited disorder of the peripheral nervous system (Skre, 1974). Autosomal dominant, autosomal recessive, and X-linked forms have been recognized. Classification On the basis of electrophysiologic properties and histopathology, CMT has been divided into primary peripheral demyelinating (type 1, or HMSNI) and primary peripheral axonal (type 2, or HMSNII) neuropathies. The demyelinating neuropathies classified as CMT type 1 are characterized by severely reduced motor NCVs (less than 38 m/s) and segmental demyelination and remyelination with onion bulb formations on nerve biopsy. The axonal neuropathies classified as CMT type 2 are characterized by normal or mildly reduced NCVs and chronic axonal degeneration and regeneration on nerve biopsy (see CMT2A1; 118210). Distal hereditary motor neuropathy (dHMN) (see 158590), or spinal CMT, is characterized by exclusive motor involvement and sparing of sensory nerves (Pareyson, 1999). McAlpine (1989) proposed that the forms of CMT with very slow nerve conduction be given the gene symbol CMT1A (118220) and CMT1B, CMT1A being the gene on chromosome 17 and CMT1B being the gene on chromosome 1. CMT2 was the proposed symbol for the autosomal locus responsible for the moderately slow nerve conduction form of the disease (axonal). For a phenotypic description and discussion of genetic heterogeneity of the various subtypes of CMT, see CMTX1 (302800), CMT2A1 (118210), CMT3 (DSS; 145900), CMT4A (214400), and CMTDIB (606482). Genetic Heterogeneity of Autosomal Dominant Demyelinating CMT1 Autosomal dominant demyelinating CMT1 is a genetically heterogeneous disorder and can be caused by mutations in different genes; see CMT1A (118220), CMT1C (601098), CMT1D (607678), CMT1E (607734), CMT1F (607734), CMT1G (618279), CMT1H (619764), CMT1I (619742), and CMT1J (620111). See also 608236 for a related phenotype characterized by isolated slowed nerve conduction velocities (NCVs). [from OMIM]

Zellweger syndrome is an autosomal recessive systemic disorder characterized clinically by severe neurologic dysfunction, craniofacial abnormalities, and liver dysfunction, and biochemically by the absence of peroxisomes. Most severely affected individuals with classic Zellweger syndrome phenotype die within the first year of life (summary by Wanders, 2004). 'Zellweger syndrome' is the prototype of a large group of peroxisomal disorders, which can be classified into 2 main groups: (1) disorders of peroxisome biogenesis and (2) single peroxisomal enzyme deficiencies (see 264470). The peroxisome biogenesis disorders (PBDs) fall into 4 main phenotypic classes. Three of them, Zellweger syndrome, neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD), have multiple complementation groups and form a spectrum of overlapping features, with the most severe being the Zellweger syndrome and the least severe infantile Refsum disease. The fourth group, rhizomelic chondrodysplasia punctata (RCDP1; 215100), is a distinct PBD phenotype (summary by Moser et al., 1995, Wanders, 2004). Heimler syndrome, a rare autosomal recessive disorder encompassing sensorineural hearing loss, enamel hypoplasia of the secondary dentition, and nail abnormalities, represents a discrete phenotypic entity at the mildest end of the PBD spectrum (Ratbi et al., 2015). Genetic Heterogeneity of Zellweger Syndrome Zellweger syndrome (denoted by the suffix 'A' in the symbol) is a genetically heterogeneous disorder and can be caused by mutation in any one of several genes, known as pexins, involved in peroxisome biogenesis. The pexin (PEX) genes encode proteins essential for the assembly of functional peroxisomes (summary by Distel et al., 1996). Forms of Zellweger syndrome include PBD1A, caused by mutation in the PEX1 gene on chromosome 7q21; PBD2A (214110), caused by mutation in the PEX5 (600414) gene on chromosome 12p13; PBD3A (614859), caused by mutation in the PEX12 (601758) gene on chromosome 17; PBD4A (614862), caused by mutation in the PEX6 (601498) gene on chromosome 6p21; PBD5A (614866), caused by mutation in the PEX2 (170993) gene on chromosome 8q21; PBD6A (614870), caused by mutation in the PEX10 (602859) gene on chromosome 1p36; PBD7A (614872), caused by mutation in the PEX26 (608666) gene on chromosome 22q11; PBD8A (614876), caused by mutation in the PEX16 (603360) gene on chromosome 11p12; PBD10A (614882), caused by mutation in the PEX3 (603164) gene on chromosome 6q23-q24; PBD11A (614883), caused by mutation in the PEX13 (601789) gene on chromosome 2p15; PBD12A (614886), caused by mutation in the PEX19 (600279) gene on chromosome 1q22; and PBD13A (614887), caused by mutation in the PEX14 gene (601791) on chromosome 1p36.2. Mutation in the pexin genes also causes the less severe phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD); see PBD1B (601539) for a phenotypic description and discussion of genetic heterogeneity of these PBDs. Heimler syndrome-1 (HMLR1; 234580) and -2 (HMLR2; 616617) are caused by mutation in the PEX1 and PEX6 genes, respectively. The rhizomelic chondrodysplasia subtype of PBD (RCDP1, PBD9; 215100), and a PBD without rhizomelia (PBD9B; 614879), are caused by mutation in the PEX7 gene (601757) on chromosome 6q22-q24. In addition to the defects in peroxisome assembly, Distel et al. (1996) noted that peroxisomal disorders include a number of single peroxisomal enzyme deficiencies: X-linked adrenoleukodystrophy (ALD; 300100), acyl-coenzyme A oxidase deficiency (264470), DHAPAT deficiency (222765), alkyl-DHAP synthase deficiency (600121), glutaric aciduria type III (231690), classic Refsum disease (266500), hyperoxaluria type I (259900), and acatalasia (115500). A peroxisomal and mitochondrial fission defect results in a lethal encephalopathy (EMPF; 614388). [from OMIM]

Mutations in the CRYBB2 gene have been found to cause several types of cataract, which have been described as congenital cerulean, 'blue dot,' Coppock-like, sutural with punctate and cerulean opacities, pulverulent embryonal, pulverulent with cortical opacities, dense posterior star-shaped subcapsular with pulverulent opacities in the cortical and embryonal regions, and dense embryonal. Before it was known that mutations in the CRYBB2 gene cause several types of cataract, the preferred title of this entry was 'Cataract, Congenital, Cerulean Type 2,' with the symbol CCA2. [from OMIM]

Mutations in the CRYGC gene have been found to cause several types of cataract, which have been described as Coppock-like; embryonic, fetal, infantile nuclear; zonular pulverulent; and lamellar. Some patients also exhibit microcornea. Before it was known that mutations in the CRYGC gene cause several types of cataract, this entry was titled 'Cataract, Coppock-like,' with the symbol CCL. [from OMIM]