Dysferlinopathy encompasses a range of disorders causing muscle weakness due to a deficiency in the dysferlin protein.
Symptoms vary widely, with some individuals having a mild course and others experiencing severe, potentially fatal symptoms. One form, Limb-Girdle Muscular Dystrophy Type 2B (LGMD2B), manifests with progressive weakness in hip, shoulder, and abdomen muscles, often requiring a wheelchair in later stages. Most individuals with LGMD2B live into adulthood, with respiratory failure as the common cause of death. Another type, Miyoshi Muscular Dystrophy Type 1 (MMD1), affects distal muscles, especially in the legs, and progresses more slowly. Other presentations include distal myopathy with anterior tibial onset (initially distal muscle weakness that progressives to the proximal muscles) and scapuloperoneal syndrome (distal muscle weakness with weakness in the shoulder muscles). There is no cure for dysferlinopathy, but physical therapy, stretching, mechanical aids, and, in severe cases, ventilators can assist with symptom management. Heart problems may require consultation with a cardiologist for appropriate treatments.
This group of conditions is caused by pathogenic (disease-causing) variants in the DYSF gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background. For example, individuals of Sephardic Jewish descent have a 1 in 10 chance to be a carrier.