Myriad Genetics provides the following resources in select languages:

Myriad Foresight® Carrier Screen

Diseases

FKRP-related disorders

What are FKRP-related Disorders?

Harmful genetic changes (mutations) in the FKRP gene can cause a wide spectrum of disorders known as limb-girdle muscular dystrophy-dystroglycanopathies (LGMD). The primary association of LGMD is limb-girdle muscular dystrophy R9 (LGMDR9), which causes muscle weakness as a result of fukutin-related protein (FKRP) deficiency 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.

Limb-Girdle Muscular Dystrophy R9

Individuals with LGMDR9 develop symptoms at variable ages, although symptoms tend to present first in adolescence. LGMDR9 does not typically affect intelligence or mental function, but some studies have shown rare brain abnormalities and cognitive dysfunction in patients. The most common symptom is muscle weakness of the hip, shoulder, and abdomen that gets worse over time. The rate at which the muscles weaken can vary, but muscle weakening often results in a wheelchair becoming necessary. Other possible features include enlarged calf muscles, shortening and hardening of muscles leading to rigid joints (contractures), prominence (winging) of the shoulder blades, and curvature of the spine (scoliosis). Respiratory complications (seen in approximately 30-50% of individuals) or heart complications (seen in over 50% of individuals) are also associated with these conditions and may lead to death.

Other FKRP-related Disorders

Mutations in the FKRP gene also cause other, more severe forms of muscular dystrophy including merosin-deficient congenital muscular dystrophy type 1C (MDC1C), muscle-eye brain disease (MEB) and Walker-Warburg syndrome (WWS). Individuals with MDC1C most often have an early age of onset (although the age of onset can vary), an inability to walk, enlarged calf muscles, and intellectual disability, and can often have brain abnormalities. Individuals with MEB and WWS are born with muscle weakness and structural abnormalities of the brain and eyes.

How common are FKRP-related Disorders?

Mutations in the FKRP gene are most often associated with LGMDR9. Autosomal-recessive LGMD has an estimated prevalence of 1 in 15,000 individuals. The percentage of LGMD that is attributed to LGMDR9 is approximately 10%. The mutations in the FKRP gene associated with other disorders, such as MDC1C, WWS, and MEB, are underrepresented in the global FKRP registry due to their severity and early onset. The exact contribution of FKRP mutations to these rarer conditions is not known.

How are FKRP-related Disorders treated?

There is no cure for any of the FKRP-related disorders, and there are few effective treatments. Physical therapy helps retain muscle strength and mobility for as long as possible. Stretching, mechanical aids, or surgery may aid in that goal. If muscle weakness begins to affect the ability to breathe, a machine that assists with breathing (a ventilator) may be needed. Cardiac surveillance is recommended, and those who develop heart problems will need to see a heart specialist (cardiologist) for treatment.

What is the prognosis for an individual with an FKRP-related Disorder?

The outlook for an individual with LGMDR9 varies. Often the earlier symptoms begin, the faster they progress; however, symptoms, onset, and prognosis can be variable. People with more severe symptoms can become wheelchair bound in their early teenage years and die in early adulthood, with death usually due to respiratory and/or cardiac complications.

Individuals with MDC1C have varied outcomes. Some die as a result of respiratory complications in the second decade of life and are never able to walk. Others retain the ability to walk into their fifth decade of life.

The prognosis for individuals with WWS/MEB is poor. Some individuals with MEB have survived into their teens, whereas individuals with WWS usually do not survive past early childhood.