Mutations in the FKRP gene lead to a range of disorders collectively known as limb-girdle muscular dystrophy-dystroglycanopathy, primarily linked to limb-girdle muscular dystrophy type 2I (LGMD2I).
LGMD2I symptoms vary widely among individuals, with some experiencing mild or nearly asymptomatic cases, while others face severe and potentially fatal symptoms. In LGMD2I, symptoms typically begin in adolescence, affecting muscles in the hip, shoulder, and abdomen. Muscle weakness progresses, often necessitating wheelchair use. Enlarged calf muscles, contractures, shoulder blade winging, and scoliosis can also occur. Respiratory complications (in 30-50% of cases) and heart issues (in over 50% of cases) may lead to fatalities. Mutations in FKRP also cause other muscular dystrophies such as merosin-deficient congenital muscular dystrophy type 1C (MDC1C), muscle-eye brain disease (MEB), and Walker-Warburg syndrome (WWS).
MDC1C is characterized by early onset, an inability to walk, enlarged calf muscles, intellectual disability, and brain abnormalities. MEB and WWS present at birth with muscle weakness, brain, and eye abnormalities. Currently, there is no cure for FKRP-related disorders, and treatments are limited. Physical therapy is recommended to maintain muscle strength and mobility. Stretching, mechanical aids, and surgery can assist in preserving muscle function. As the condition progresses, breathing support like ventilators might be necessary. Regular cardiac monitoring is essential, and symptomatic treatments should be consulted with a cardiologist for those who develop heart problems.
These conditions are caused by pathogenic (disease-causing) variants in the FKRP 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. Carriers typically do not experience any symptoms.
Other names for this condition include muscular dystrophy-dystroglycanopathy and limb-girdle muscular dystrophy R9.
Resources:
Muscular Dystrophy Association
Limb Girdle Muscular Dystrophy Awareness Foundation
Revised October 2023
