Facioscapulohumeral Muscular Dystrophy (FSHD) in India: Genetic Insights & Recent Advances in Diagnostics and Therapeutics

Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent skeletal muscle disorder characterized by progressive, asymmetric muscle weakness, particularly affecting the face, shoulders, and upper arms. Although estimates in India are unavailable, it is fairly common in the Caucasian population, with prevalence rates ranging from 1 in 8000 to 1 in 20,000. The typical age of onset of symptoms is in the second decade of life, with some severe cases exhibiting symptoms before the age of 5 years; however, there is a wide variation in the order and progression rate of affected muscles. Classical features, such as scapular winging and foot drop, affect the patient’s quality of life. FSHD is an autosomal dominant inherited disease caused by epigenetic derepression of the 4q35 D4Z4 macrosatellite array, leading to the expression of the toxic DUX4 protein in adult muscles. Contraction of the D4Z4 array to <10 repeats is believed to cause the derepression of this region. Its unique etiology, the large size of the repeats (~3.2 kb), and significant clinical variability make diagnosis and care challenging. Diagnosis is based on characteristic clinical features and confirmed by DNA testing using Southern blotting. Underdiagnosis due to the nonavailability of diagnostic testing in the country is only now being addressed by the availability of newer techniques, such as optical genome mapping. In this context, this review provides an overview of clinical presentation, disease mechanisms, and recent developments in research and diagnostics worldwide in FSHD and focuses on providing an Indian perspective based on the limited information available.