Expanding the Genotypic Spectrum of POMGNT1-Related Muscle-Eye-Brain Disease: A Case Report.

backgroundMuscle-Eye-Brain disease (MEB) is a rare autosomal recessive dystroglycanopathy caused by defective glycosylation of α-dystroglycan, leading to a multisystem disorder involving the central nervous system, skeletal muscle, and eyes. It represents an important cause of developmental and epileptic encephalopathy, with variable clinical severity and genetic heterogeneity, most commonly associated with variants in the POMGNT1 gene.

methodsClinical, neurophysiological, neuroimaging, histopathological, and genetic investigations were performed, including targeted next-generation sequencing for congenital muscular dystrophy-associated genes.

resultsThe patient presented with early-onset hypotonia, global developmental delay, progressive motor regression, intellectual disability, and ocular abnormalities. Epilepsy onset occurred in childhood and evolved into drug-resistant epilepsy with status epilepticus in adulthood. Brain MRI revealed lissencephaly, ventriculomegaly, and brainstem and cerebellar hypoplasia. EEG demonstrated features consistent with epileptic encephalopathy. Genetic testing identified compound heterozygosity for the POMGNT1 variants c.1282C>T, p.(Gln428*) and c.793C>T, p.(Arg265Cys). Seizure control was eventually achieved with polytherapy including four antiseizure medications.

conclusionThis case expands the genotypic and phenotypic spectrum of POMGNT1-related MEB, highlighting the potential for severe epilepsy and status epilepticus in adulthood. It also underscores the importance of long-term clinical follow-up and suggests that aggressive antiseizure treatment may achieve seizure control even in advanced stages of the disease.