Fukuyama congenital muscular dystrophy (FCMD) is characterized by hypotonia, symmetric generalized muscle weakness, and CNS migration disturbances that result in changes consistent with cobblestone (previously type II) lissencephaly with cerebral and cerebellar cortical dysplasia. Mild, typical, and severe phenotypes are recognized. Onset typically occurs in early infancy, with a poor suck, weak cry, and floppiness. Affected individuals have contractures of the hips, knees, and interphalangeal joints. Later features include myopathic facial appearance; pseudohypertrophy of the calves and forearms; motor and speech retardation and intellectual disability; convulsions; ophthalmologic abnormalities including visual impairment and retinal dysplasia; and progressive cardiac involvement in individuals over age ten years. Swallowing disturbance occurs in individuals with severe FCMD and in individuals over age ten years, leading to recurrent aspiration pneumonia and death.
The diagnosis of FCMD is established by clinical findings and characteristic findings on neuroimaging, electromyography, measurement of serum creatine kinase concentration, muscle biopsy, and molecular genetic testing. FKTN (formerly FCMD) is the only gene known to be associated with FCMD. Molecular genetic testing of FKTN is available on a clinical basis
FCMD is inherited in an autosomal recessive manner. At conception, the sibs of an affected individual have a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once an at-risk sib is known to be unaffected, the risk of his/her being a carrier is 2/3. When the mutations have been identified in the proband, carrier testing for at-risk family members and prenatal diagnosis for pregnancies at increased risk are possible.