Authors:

Gaurang Sindhav, Mohammadfesal I. Ghanchi, Pooja G. Trivedi, Anil K. Shah

Abstract:

Limb-Girdle Muscular Dystrophy 1D (OMIM#603511) and Becker Muscular Dystrophy (OMIM#300376) represent distinct clinical and genetic paradigms: while LGMD1D manifests as an adult-onset, progressive form with an autosomal dominant inheritance, BMD typically presents as a milder, variable-onset phenotype arising from in-frame deletions in the DMD gene, inherit by X-linked recessive pattern. In the present case, in a clinically identified 25-year-old BMD proband, Next-Generation Sequencing (NGS) revealed a rare genomic co-occurrence of variants in DNAJB6 (exon 9, c.709G>C; p.Ala237Pro) and DMD (deletion of exons 45-47). This dual molecular diagnosis highlights the extreme genetic heterogeneity of Muscular Dystrophies (MDs). Physical examination revealed symptoms, including Gowers’ sign, calf hypertrophy, and toe walking, alongside frequent falls, dysarthria, and distal muscle weakness. Biochemical analysis confirmed severe myopathy, characterized by a 26-fold elevation in Creatine Phosphokinase (CPK) aligning with BMD and an 8-fold increase in urinary microprotein, indicating significant muscle fiber breakdown and secondary protein excretion.  To our knowledge, this case marks the first clinical report of a novel LGMD1D variant coexisting with BMD. This case expands the mutational spectrum of MDs by identifying a rare dual genetic pathology and emphasizes the importance of comprehensive molecular diagnostics, accurate genotype-phenotype correlation, and genetic counseling in managing complex neuromuscular disorders. The lack of muscle biopsy and Western blot analysis, however, limits direct evaluation of histopathological changes and protein expression.

Keywords:

LGMD1D, BMD, Genetic Diagnosis, Co-occurrence

Vol & Issue:

VOL.18, ISSUE No.1, March 2026