Variability in Disease Severity in Siblings With Homozygous Missense Variant of ADSSL1: Clinical Genetic Study and Review of Literatures.

Background: Distal myopathies are genetic muscle disorders caused by mutations in various genes. A study found that mutations in adenylosuccinate synthetase-like 1 (ADSSL1) are associated with distal myopathy in nine patients from six unrelated families in South Korea. Previous research showed that affected individuals experienced distal muscle weakness starting in adolescence, along with mild facial muscle weakness, slightly elevated or normal serum creatine kinase (CK) levels, and the presence of a few rimmed vacuoles in muscle fibers or minimal chronic myopathic damage. Previously reported patients in this category exhibited an early age of symptom onset and severe muscle weakness. In this study, we present a case of two sisters who share the same mutation locus but display distinct disease phenotypes.

Methods: A literature review was conducted on distal myopathies in patients with ADSSL1 mutations, alongside a retrospective analysis of disease severity variability among siblings with a homozygous missense variant of ADSSL1.

Results: The study focuses on two sisters with differing disease manifestations despite carrying the same genetic mutation. The older sister showed lower ability in running and jumping compared to her peers at age 7 and experienced notable muscle weakness and atrophy by age 27, whereas the younger sister remained free of symptoms at age 30.

Conclusion: These findings suggest that mutations at the same locus can result in varying disease outcomes, emphasizing the complexity of predicting disease progression based solely on genetic mutations.