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. 2008 Feb;29(2):301-5.
doi: 10.3174/ajnr.A0792. Epub 2007 Nov 1.

Hypomyelination and congenital cataract: neuroimaging features of a novel inherited white matter disorder

A Rossi  1 , R Biancheri, F Zara, C Bruno, G Uziel, M S van der Knaap, C Minetti, P Tortori-Donati
Affiliations

Hypomyelination and congenital cataract: neuroimaging features of a novel inherited white matter disorder

A Rossi et al. AJNR Am J Neuroradiol. 2008 Feb.

Abstract

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.

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Figures

Fig 1.
Fig 1.
HCC: early stage (patient 8, 20 months of age). Axial (A) and coronal (B) T2-weighted images (4157/100/2, TR/TE/NEX) show diffuse hyperintensity of the deep, periventricular, and capsular white matter with local sparing of the subcortical white matter (arrows, A and B) and callosal genu (arrowheads, A). The cerebellum is fully myelinated (B).
Fig 2.
Fig 2.
HCC: intermediate stage (patient 6, 8 years of age). A, Axial T1-weighted image (513/12/2, TR/TE/NEX) shows diffuse mild hypointensity of the supratentorial white matter, resulting in blurred gray-white matter interface, consistent with hypomyelination. B, Axial T2-weighted image (4500/108/4, TR/TE/NEX) shows moderate diffuse white matter hyperintensity, also consistent with hypomyelination. Note that the signal intensity is significantly lower than that of CSF. C, Coronal T2-weighted image (4531/112/4, TR/TE/NEX) shows mild hyperintensity of the white cores of the cerebellar hemispheres as well as residual myelination of the medullary laminae (arrows).
Fig 3.
Fig 3.
HCC: intermediate and chronic stages (patient 7). A, Axial T1-weighted image (437/16/2, TR/TE/NEX) obtained at 8 years of age shows hypointense deep and periventricular white matter, with an anterior-to-posterior gradient of severity. B, Axial T2-weighted image (4000/96/2, TR/TE/NEX) obtained at 8 years of age shows marked white matter hyperintensity, paralleling that of CSF and prevailing in the frontal regions. C, Axial DWI obtained at 15 years of age shows shrunken white matter with markedly increased diffusivity. The ADC value in deep frontal white matter was 2.094 mm2/s. D, Axial T2-weighted image (4157/100/2, TR/TE/NEX) confirms shrinkage of affected white matter (compare with B).
Fig 4.
Fig 4.
MR spectroscopy findings (patient 8, 20 months of age). On the upper right image corners, axial T2-weighted images (4157/100/2, TR/TE/NEX) show localization of an 18 × 18 × 18 mm region of interest over the right posterior periventricular white matter. A, Short echo-time MR spectrum (PRESS; 2000/23 ms, TR/TE) shows elevation of mIns/Cr and Cho/Cr ratios, normal NAA/Cr ratio, and abnormally elevated lipid peak at 1.29 ppm. B, Intermediate echo-time MR spectrum (PRESS; 2000/144 ms, TR/TE) confirms elevated Cho/Cr and normal NAA/Cr.
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