Hypomyelination and congenital cataract: Identification of novel mutations in two unrelated families

Background: Hypomyelination and congenital cataract (HCC) is a rare autosomal recessive white matter disorder characterized by congenital cataract, progressive neurologic impairment, and myelin deficiency in the central and peripheral nervous system, caused by mutations in the FAM126A gene. Aims: To report three patients of two unrelated families segregating novel mutations. Methods: clinical, neurophysiological, neuroradiologic and molecular investigations were carried out. Results: All patients show bilateral congenital cataract and progressive neurological impairment with peripheral neuropathy. The clinical phenotype is consistent with the severe form of HCC. Brain magnetic resonance imaging show the combination of a diffuse hypomyelination with superimposed periventricular white matter signal abnormalities. Conclusions: this study describes three additional HCC patients indicating that this recently defined leukoencephalopathy should be included in the differential diagnosis of hypomyelination in childhood. The peculiar clinical and neuroradiologic findings are useful to properly address molecular investigations and allow the differential diagnosis between HCC and other hypomyelinating forms.