Phenotypic characterization of hypomyelination and congenital cataract.

OBJECTIVE: To define the clinical and laboratory findings in a novel autosomal recessive white matter disorder called hypomyelination and congenital cataract, recently found to be caused by a deficiency of a membrane protein, hyccin, encoded by the DRCTNNB1A gene located on chromosome 7p21.3-p15.3.

METHODS: We performed neurological examination, neurophysiological, neuroimaging, and neuropathological studies on sural nerve biopsy in 10 hypomyelination and congenital cataract patients from 5 unrelated families.

RESULTS: The clinical picture was characterized by bilateral congenital cataract, developmental delay, and slowly progressive neurological impairment with spasticity, cerebellar ataxia, and mild-to-moderate mental retardation. Neurophysiological studies showed a slightly to markedly slowed motor nerve conduction velocity in 9 of 10 patients, and multimodal evoked potentials indicated increased central conduction times. Neuroimaging studies demonstrated a diffuse supratentorial hypomyelination, with in some patients, additional areas of more prominent signal change in the frontal region. Sural nerve biopsy showed a slight-to-severe reduction in myelinated fiber density, with several axons surrounded by a thin myelin sheath or devoid of myelin.

INTERPRETATION: Hypomyelination and congenital cataract is a novel autosomal recessive white matter disorder characterized by the unique association of congenital cataract and hypomyelination of the central and peripheral nervous system.