First familial limb-girdle muscular dystrophy 2L in China: Clinical, imaging, pathological, and genetic features

Limb-girdle muscular dystrophy 2L (LGMD2L) is mainly characterized by late adult onset, atrophy of proximal muscles, chronic progressive and asymmetric weakness, accompanied by increased creatine kinase (CK) levels, dystrophic pathological changes and electromyography showing myogenic damage. To date, familial LGMD2L was reported in European countries and had not been reported in China. A careful investigation of the clinical manifestations, muscle performance imaging, biopsy, and target next-generation sequencing (NGS) technology was utilized to identify pathogenic genetic variants in a 4-generation pedigree that includes 6 affected individuals. The results revealed mild-to-moderate hypertrophy of bilateral gastrocnemii and slight weakness and atrophy in the proximal muscles of the lower limbs, with obviously increased serum creatine kinase levels. The symptoms were more serious in the male proband but were also observed in females. Obvious and symmetric atrophy and fat infiltration of posterior segments of the thigh was evident in muscle magnetic resonance imaging (MRI). The pathological changes included a small amount of atrophic and hypertrophic fibers, scattered necrotizing fibers, a small number of increased nuclei, inward migration, mild proliferation of interstitial connective tissue, and no inflammatory cell infiltration. The pathogenic allele was a c.220C > T mutation in the anoctamin 5 (ANO5) gene. The LGMD2L family was characterized by mild chronic myopathy and bilateral gastrocnemius hypertrophy with obviously increased CK levels. Pathological changes included atrophy of fibers with interstitial connective tissues hyperplasia. The pathogenic allele was a c.220C> T mutation in the ANO5 gene.