Hypomyelination and congenital cataract: broadening the clinical phenotype

Objective: To further delineate the clinical spectrum of hypomyelination and congenital cataract (HCC), a rare autosomal recessive white matter disorder due to deficiency of a membrane protein, hyccin, encoded by FAM126A. Design: Case reports and literature review. Setting: University hospital. Patients: Nine additional patients with HCC. Results: Cataract was congenital in 5 patients; it was found at 4, 5, and 7 months in 3 patients, and only a mild lens opacity was noted at age 3 years in the remaining patient. Neurologic presentation was at birth in 1 child, was characterized by developmental delay at the end of the first year of life in 7 patients, and was characterized by sudden motor regression in the second year of life in the remaining patient. Three patients were able to walk with support only, 5 achieved the ability to walk without support, and theremaining patient was not able to stand at age 2 years. Mental retardation was present in all patients. Peripheral neuropathy was present in the 8 patients who underwent neurophysiological investigations. Brain magnetic resonance imaging showed hypomyelination associated with periventricular white matter abnormalities in all patients and brainstem pyramidal tract involvement in 8. Molecular analysis depicted 3 novel mutations and the previously reported IVS5 + 1G>T mutation. Conclusions: Our study broadens the clinical spectrum of HCC. The clinical variability ranges from severe early-onset neurologic impairment to a milder phenotype. In contrast to this clinical variability, the peculiar magnetic resonance pattern of hypomyelination combined with increased periventricular white matter water content allows distinction of HCC from other forms of hypomyelinating leukoencephalopathies. ©2011 American Medical Association. All rights reserved.