OMIM ID:
Cataracts, Congenital, and Hypomyelinating Leukodystrophy
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Bilateral cataracts may be present at birth or later in the first decade of life. The ERG and flash VEPs are normal.
Systemic Features
Psychomotor development is initially normal but signs of delay are usually present during the first year of life. Patients may be able to walk but only with support. Pyramidal and cerebellar dysfunction, muscle weakness and wasting, dysarthria, truncal hypotonia, intention tremor, and spasticity are evident during the first decade. Some have seizures. Cognitive impairment ranges from mild to moderate. Most patients become wheelchair-bound late in the first decade of life and some do not survive beyond childhood.
Hypomyelination and mild axonal loss may be seen in peripheral nerve biopsies while neuroimaging shows evidence of diffuse and progressive cerebral white matter atrophy.
Genetics
Inheritance
This is an autosomal recessive disorder caused by homozygous mutations in FAM126A (7p15.3) leading to a deficiency of the neuronal protein hyccin. The result is deficient myelination in both central and peripheral nervous systems. No symptoms are evident in heterozygotes.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.