Mutations in the FKRP gene may cause a wide spectrum of disorders known as limb-girdle muscular dystrophy-dystroglycanopathy, but has primarily been associated with limb-girdle muscular dystrophy type 2I (LGMD2I). LGMD2I causes muscle weakness as a result of a deficiency of the fukutin-related protein (FKRP) found in skeletal and cardiac muscle. Symptoms of the disease vary greatly from person to person, even among people in the same family. Some people with the disease can have a mild course where they are nearly asymptomatic, while others may have severe symptoms that can be fatal.
People with LGMD2I develop symptoms at variable ages, though symptoms tend to first present in adolescence. LGMD2I does not typically affect intelligence or mental function though some studies have shown rare brain abnormalities and cognitive dysfunction; the most common symptom is progressive muscle weakness of the hip, shoulder, and abdomen. The rate at which the muscles weaken can vary, but many experience progressive weakness to a point where a wheelchair becomes necessary. Other possible features include enlarged calf muscles, contractures, winging of the shoulder blade, and scoliosis. Respiratory complications (~30-50% of individuals) or heart complications (>50% of individuals) are also associated with these conditions, and may be a cause of death.
Mutations in the FKRP gene also cause other forms of muscular dystrophy including merosin-deficient congenital muscular dystrophy type1C (MDC1C), muscle-eye brain disease (MEB) and Walker-Warburg syndrome (WWS).
Individuals with MDC1C have most often have an early age of onset (although it can vary), an inability to walk, enlarged calf muscles, intellectual disability, and often have brain abnormalities.
Individuals with MEB and WWS are born with muscle weakness and structural abnormalities of the brain and eyes.
Mutations in the FKRP gene are most often associated with LGMD2I. Autosomal recessive LGMD has an estimated prevalence of 1 in 15,000 individuals. The percentage of LGMD that is attributed to LGMD2I is approximately 10%. Rarely, mutations in the FKRP gene are associated with other disorders such as MDC1C, WWS, and MEB.
There is no cure for any of the FKRP-related disorders and there are few effective treatments. Physical therapy is often recommended to retain muscle strength and mobility for as long as possible. Stretching, mechanical aids, or surgery may aid in that goal. As muscles deteriorate, a ventilator may be required to aid breathing. Cardiac surveillance is recommended, and those who develop heart problems should consult with a cardiologist for symptomatic treatments.
The outlook for a person with LGMD2I varies. Generally speaking, the earlier symptoms begin, the faster they progress. However, because symptoms and onset can be variable, prognosis can be variable. People with more severe symptoms can become wheelchair bound in their early teens and die in early adulthood with death usually being due to respiratory and/or cardiac complications.
Individuals with MDC1C have a range of outcomes. Some are never able to walk and die as a result of respiratory complications in the second decade of life, while others have been reported to retain the ability to walk into their fifth decade of life.
The prognosis for individuals with WWS/MEB is poor. Some individuals with MEB may survive until their teens, whereas individuals with WWS usually do not survive past early childhood.
Explanations of an extensive number of genetic diseases written for the public by the U.S. government's National Institutes of Health.
This group organizes Limb Girdle Muscular Dystrophy Awareness Day and aims to increase awareness of the condition globally.
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