The portal for rare diseases and orphan drugs

The disease has a high prevalence in the Japanese population due to an ancestral mutation, and is extremely uncommon elsewhere. The prevalence of Fukuyama type muscular dystrophy (FCMD) in Japan is estimated at 1/25,000-50,000 live births.

Disease onset typically occurs in early infancy. Initial symptoms include a poor suck, weak cry, floppiness and developmental delay. Symmetrical generalized muscle weakness and hypotonia are present. With time, patients develop retractile phenotype and show contractures of the hips, knees and interphalangeal joints. Later features include myopathic facial appearance, pseudohypertrophy of the calves and forearms, and ophthalmologic abnormalities (visual impairment and retinal dysplasia). Progressive cardiac involvement, respiratory failure and swallowing and feeding disturbances (leading to recurrent aspiration pneumonia and death) occur in infants with severe FCMD and in patients over ten years of age. Seizures (generalized tonic-clonic convulsions, complex partial seizures and partial seizures with secondary generalization, infantile spasms, tonic seizures and myoclonic seizures) occur in over 50% of affected individuals (median age of seizure onset 1-3 years of age). All patients with the Japanese ancestral mutation show severe intellectual deficit and the intelligence quotient (IQ) is usually between 30 and 60.

It is caused by mutations in the fukutin gene (FKTN; 9q31-q33). Of note, FKTN variants are responsible for a clinical spectrum ranging from CMD without brain involvement to isolated, dilated cardiomyopathy.

The diagnosis is based on the clinical picture, characteristic neuroimaging and electromyography findings, muscle biopsy results, and molecular genetic testing.

Differential diagnoses include Duchenne and Becker muscular dystrophies, and other muscular dystrophies associating a type II lissencephaly (known as dystroglycanopathies). Brain, cerebellar and ocular abnormalities observed in most FCMD patients are similar to and would be diagnosed out of Japan as MEB syndrome. Therefore, there is an increasing tendency to use the global term MEB/FCMD syndrome.

Prenatal diagnosis is possible where the pathogenic variant has previously been identified in a family member.

Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them that there is a 25% risk of having an affected child at each pregnancy.

Management includes physiotherapy, treatment of orthopedic, respiratory and cardiac complications, respiratory aid, and medical or surgical treatment for nutritional and gastrointestinal problems. Control of seizures requires antiepileptic drugs. Surveillance includes monitoring for respiratory and cardiac function.

Prognosis depends on the severity of complications, mainly neurologic, cardiac or respiratory.