Subject(s)
Central Nervous System Cysts/diagnosis , Craniofacial Abnormalities/diagnosis , Hereditary Central Nervous System Demyelinating Diseases/diagnosis , Prenatal Diagnosis , Base Sequence , Central Nervous System Cysts/congenital , Central Nervous System Cysts/genetics , Cephalometry , Child , Child Development , DNA Mutational Analysis/methods , Female , Hereditary Central Nervous System Demyelinating Diseases/congenital , Hereditary Central Nervous System Demyelinating Diseases/genetics , Humans , Infant , Membrane Proteins/genetics , Pedigree , PregnancyABSTRACT
BACKGROUND AND PURPOSE: Hypomyelination and congenital cataract (HCC) is an autosomal recessive white matter disease caused by deficiency of hyccin, a membrane protein implicated in both central and peripheral myelination. We aimed to describe the neuroimaging features of this novel entity. MATERIALS AND METHODS: A systematic analysis of patients with unclassified leukoencephalopathies admitted to our institutions revealed 10 children with congenital cataract, slowly progressive neurologic impairment, and diffuse white matter abnormalities on neuroimaging. Psychomotor developmental delay was evident after the first year of life. Peripheral neuropathy was demonstrated by neurophysiologic studies in 9 children. The available neuroimaging studies were retrospectively reviewed. RESULTS: In all patients, neuroimaging revealed diffuse involvement of the supratentorial white matter associated with preservation of both cortical and deep gray matter structures. Supratentorial white matter hypomyelination was detected in all patients; 7 patients also had evidence of variably extensive areas of increased white matter water content. Deep cerebellar white matter hypomyelination was found in 6 patients. Older patients had evidence of white matter bulk loss and gliosis. Proton MR spectroscopy showed variable findings, depending on the stage of the disease. Sural nerve biopsy revealed hypomyelinated nerve fibers. Mutations in the DRCTNNB1A gene on chromosome 7p15.3, causing complete or severe deficiency of hyccin, were demonstrated in all patients. CONCLUSIONS: HCC is characterized by a combined pattern of primary myelin deficiency and secondary neurodegenerative changes. In the proper clinical setting, recognition of suggestive neuroimaging findings should prompt appropriate genetic investigations.
Subject(s)
Brain/pathology , Cataract/congenital , Cataract/diagnosis , Hereditary Central Nervous System Demyelinating Diseases/congenital , Hereditary Central Nervous System Demyelinating Diseases/diagnosis , Image Enhancement/methods , Magnetic Resonance Imaging/methods , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Nerve Fibers, Myelinated/pathology , Retrospective Studies , SyndromeABSTRACT
Congenital hypomyelinating neuropathy (CHN; MIM# 605253) is a severe neuropathy with early infancy onset inherited as an autosomal dominant or recessive trait. Sural nerve biopsy shows a characteristic picture of nonmyelinated and poorly myelinated axons with basal lamina onion bulbs and lack of myelin breakdown products. Several mutations in the MTMR2, PMP22, EGR2, and MPZ genes have been found in patients with CHN. The authors describe the clinical and morphologic features of a patient with CHN and the identification of a novel Thr124Lys mutation in the MPZ gene.
