Proximal predicament: A clinical journey to limb-girdle muscular dystrophies type 2B

Abstract

Limb-girdle muscular dystrophies (LGMDs) represent a heterogeneous group of genetically inherited myopathies characterized by progressive proximal muscle weakness. LGMD Type R2 (formerly 2B), caused by mutations in the DYSF gene encoding dysferlin, often presents with insidious lower limb weakness and elevated creatine kinase (CK) levels. This report highlights a case with characteristic clinical features and a confirmatory genetic diagnosis. We present a 41-year-old right-handed male with progressive lower limb weakness over 8 years and upper limb involvement for the past 3 years. Clinical examination revealed proximal muscle wasting with preservation of distal strength, especially in hand and foot muscles. Notable signs included wasting of bilateral biceps and quadriceps with the presence of “lumpy-bumpy” biceps and a “diamond sign” in the thighs. Serum CK levels were elevated. Whole-exome sequencing identified a homozygous missense mutation (p.Tyr1014Cys) in exon 29 of the DYSF gene, consistent with a diagnosis of LGMD R2 (dysferlinopathy). Supportive management with physiotherapy and multivitamin supplementation was initiated.