Fukuyama Congenital Muscular Dystrophy

Excerpt

Clinical characteristics: Fukuyama congenital muscular dystrophy (FCMD) is characterized by hypotonia, symmetric generalized muscle weakness, and CNS migration disturbances that result in changes consistent with cobblestone lissencephaly with cerebral and cerebellar cortical dysplasia. Mild, typical, and severe phenotypes are recognized. Onset typically occurs in early infancy with 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 delays, intellectual disability, seizures, ophthalmologic abnormalities including visual impairment and retinal dysplasia, and progressive cardiac involvement after age ten years. Swallowing disturbance occurs in individuals with severe FCMD and in individuals older than age ten years, leading to recurrent aspiration pneumonia and death.

Diagnosis/testing: The diagnosis of FCMD is established in a proband by identification of biallelic pathogenic variants in FKTN on molecular genetic testing.

Management: Treatment of manifestations: Physical therapy and stretching exercises, treatment of orthopedic complications, assistance devices such as long leg braces and wheelchairs, use of noninvasive respiratory aids or tracheostomy, prompt treatment of acute respiratory tract infections, anti-seizure medication, medical and/or surgical treatment for gastroesophageal reflux, gastrostomy tube placement when indicated to assure adequate caloric intake, cardiomyopathy treatment as per cardiologist.

Surveillance: Monitor:

1. Respiratory function in individuals with advanced disease;

2. For myocardial involvement by chest radiography, EKG, and echocardiography in individuals older than age ten years;

3. Gastrointestinal function, and for signs/symptoms of gastroesophageal reflux;

4. For foot deformities and scoliosis.

Genetic counseling: FCMD is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has 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. Carrier testing for at-risk family members and prenatal diagnosis for pregnancies at increased risk are possible if the pathogenic variants in the family are known.