Congenital Muscular Dystrophy with Severe Central Nervous System Involvement in a Patient with aHomozygous Mutation in the POMGNT1 Gene

Abstract

Congenital muscular dystrophies involving the central nervous system are genetically and clinically heterogeneous group of diseases, with clinical presentation ranging from isolated muscle involvement to severe central nervous system and eye involvement. Congenital muscular dystrophies may be due to defects in the glycosylation of α-dystroglycan because of mutations in genes encoding specific glycosyltransferases: POMT1, POMT2, POMGnT, FCMD, FKRP, LARGE. Mutations in the same gene may cause different variants of CMD.

 The aim of this report is to present a case of congenital muscular dystrophy – „ muscle- eye-brain disease” in a patient with pathological variant in the POMGNT1 gene (protein O-mannose beta 1,2-N-acetylglucosaminyltransferase) with central nervous system and eye involvement.

The patient is a 5-year-old girl with hydrocephalus, detected prenatally by ultrasound and confirmed in 8 lunar month by fetal magnetic resonance imaging. . The child is unable to walk alone and is severely mentally retarded, with pronounced hypotonia, symptomatic epilepsy, bilateral convergent strabismus, myopia (-8D), astigmatism and dysmorphic facial features. Biochemical studies showed high creatine phosphokinase (6014 U/l), electromyography revealed evidence for myopathy and neuroimaging showed severe involvement of central nervous system – ventriculomegaly and congenital cortical brain malformations. Whole exome sequencing was performed and homozygous pathological variant in the PОMGNT1 gene was detected.

Key words: pathological variant in POMGNT1 gene, congenital muscular dystrophy,  „muscle-eye-brain disease”, cortical brain malformations, ocular involvement.

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Address for correspondence:

Clinic for nervous diseases for children,
UMBALNP “Sv. Naum”
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