KLHL9-linked distal myopathy: a second family suggesting broad phenotypic variability

Distal myopathies comprise a clinically and genetically diverse group of muscle disorders characterized by initial involvement of the distal extremities. We describe siblings who developed progressive weakness in the ankle plantar flexors from adolescence to early adulthood. By their 50s, the lower legs exhibited severe fatty degeneration with pronounced involvement of the gastrocnemius and soleus. Genetic analysis identified a heterozygous p.L95F variant in KLHL9, previously associated with an early-onset autosomal dominant form of distal myopathy featuring tibialis anterior atrophy and sensory deficits. Though considering himself unaffected, the father harbored the same variant and exhibited an extremely mild phenotype. Muscle biopsy revealed chronic myopathic changes with normal expression of KLHL9. This may represent the second reported family with a KLHL9 variant, and is worth establishing KLHL9-linked distal myopathy. The combination of shared and distinct findings from the original family broadens the clinical phenotype and provides insight into the disease.