A child of congenital muscular dystrophy-dystroglycanopathy with a novel variant in the gene: a case report and literature review.

BACKGROUND

Dystroglycanopathy is a genetically heterogeneous group of rare muscular dystrophies that affect the brain, muscles, and eyes, primarily resulting from impaired glycosylation of α-dystroglycan. In this study, we identify and characterize a novel heterozygous gene variant causally associated with α-dystroglycanopathy.

CASE DESCRIPTION

We present a case of a 1-year and 5-month-old female with elevated creatine kinase (CK) levels and seizures, along with global developmental delay, microphthalmia, hypotonia, and myasthenia. Notably absent was ocular involvement. The serum CK levels typically fluctuated between 2,356 and 9,555 U/L. Video-electroencephalogram monitoring demonstrated abnormal discharge in the left anterior frontal region. Brain magnetic resonance imaging revealed numerous subcortical cysts in the bilateral cerebellar hemispheres and corpus callosum dysplasia. We performed whole-exome sequencing to identify compound heterozygous mutations in the gene [Online Mendelian Inheritance in Man (OMIM): 614643]. The identified mutations include the pathogenic variant c.1251G>A (p. Gln 417=) inherited from father, and the c.1119+2T>G variant inherited from mother. We confirm that c.1119+2T>G was a novel splice-site variant. Based on the clinical manifestations, ancillary tests, and genetic results, the patient was diagnosed with congenital muscular dystrophy with mental retardation (CMD-MR). Levetiracetam effectively controlled the seizures. However, the patient's motor and cognitive impairments remained unaddressed by pharmacological interventions and persisted backward.

CONCLUSIONS

We present a case of α-dystroglycanopathy caused by a novel splice site variant, c.1119+2T>G, in the gene. The patient presented with clinical features characteristic of CMD-MR, thus extending the phenotypic spectrum of α-dystroglycanopathy.