Muscle-Eye-Brain disease

Abstract

A term female infant was evaluated for global developmental delay, hypotonia, hyporeflexia, diffuse weakness including facial muscles, and visual impairment with optic nerve hypoplasia. In the absence of family history or perinatal concerns, an extensive investigation was performed, including lab studies, muscle biopsy, brain MRI and focused genetic testing. This revealed elevated serum CK, a structurally abnormal brain, and a dystrophic-appearing muscle biopsy with evidence of a glycosylation defect in the alpha-dystroglycan complex. Of the 6 known related genes, testing of the POMGnT1 gene showed three heterozygous missense mutations. Thus her history, examination, biopsy specimen, imaging, laboratory, and genetic studies are all consistent with the diagnosis of Muscle-Eye-Brain (MEB) disease. MEB is one of an emerging spectrum of congenital disorders that involve both central and peripheral nervous systems, described further in this case report.

FIGURE 1

A, Quadriceps biopsy (magnification, 40×) with staining for alpha-dystroglycan for normal control compared with our patient. B, Western blot testing showed decreased abundance of glycosylated alpha-dystroglycan compared with control (arrow) (expected molecular weight 156 kDa).

FIGURE 2

Magnetic resonance imaging of patient’s brain. A, Axial T2 image showing diffuse symmetric cortical malformation characterized by nodular appearing cortex or “cobblestone cortex.” There is also abnormal myelination with diffuse hyperintensities involving deep periventricular and subcortical white matter. B, Sagittal T1 image showing hypoplastic mesencephalon, pons, cerebellum, and medulla. Tectum is thickened. C, Coronal FLAIR image showing multiple cerebellar cysts (arrow).