X-linked Emery-Dreifuss muscular dystrophy caused by a novel FHL1 mutation: A case report

This study characterizes a multigenerational family with X-linked Emery-Dreifuss muscular dystrophy associated with a novel FHL1 mutation (c.746G>A, p.Cys249Tyr). Among 21 family members, 5 were affected and 3 had died. The affected individuals exhibited progressive limb weakness and muscle atrophy; classical joint contractures were absent or minimal. The proband presented with mild muscle wasting and sinus tachycardia without structural cardiac abnormalities. Electromyography revealed myopathic changes with preserved nerve conduction. Thigh magnetic resonance imaging demonstrated bilateral reduction of muscle volume with fatty infiltration, and muscle biopsy confirmed variable fiber size, degeneration, and mild fibrosis consistent with a myogenic pattern. Genetic testing identified six affected members carrying the hemizygous FHL1 c.746G>A variant, resulting in a cysteine-to-tyrosine substitution at codon 249. These findings expand the genotypic and phenotypic spectrum of FHL1-related X-linked Emery-Dreifuss muscular dystrophy, highlight the marked clinical and genetic heterogeneity of the disorder, and provide important insights into early diagnosis, phenotype prediction, and genetic counseling of the affected families.