Fukuyama Type Congenital Muscular Dystrophy

Introduction

Fukuyama-type congenital muscular dystrophy is characterized by symmetric generalized muscle weakness, hypotonia, and central nervous system migration disturbances that lead to changes consistent with cobblestone lissencephaly with cerebellar and cerebral cortical dysplasia. Severe, typical, and mild subtypes are identified.

Onset is frequently seen in early infancy presenting with a weak cry, poor suck, and floppiness. Individuals affected have contractures of the knees, hips, and interphalangeal joints. Other features include pseudohypertrophy of the calves and forearms, myopathic facial appearance, intellectual disability, motor and speech disabilities, seizures, ophthalmologic abnormalities involving visual impairment, retinal dysplasia, and progressive cardiac involvement after the age of ten.

What Are the Clinical Characteristics of Fukuyama-Type Congenital Muscular Dystrophy?

Fukuyama-type congenital muscular dystrophy involves dystrophic changes in the skeletal muscles and central nervous system migration disruptions leading to cerebral and cerebellar cortical dysplasia.

The clinical features include:

• Hypotonia.

• Weakness.

• Psychomotor retardation.

The phenotypic features range from Walker-Warburg syndrome in a severe form to the cases in which limb-girdle muscular dystrophy is seen. The onset of the disease is typical in early infancy. Symptoms include poor crying, weak suck, motor developmental delay, and floppiness. Hypotonia and symmetric muscle weakness may be present.

Some of the infants present poor weight gain. Proximal hypotonia presents as the extensibility of the trunk and shoulders. Limitations of hip abduction, hip extension, and knee extension are observed, which increase with time. Pseudohypertrophy of the calves, forearms, and ‘puffy cheeks’ are prominent in late infancy. Muscles may be hard in consistency with a fibrous texture. Myopathic facies (facial muscle involvement) occur from six to twelve months and are observed to increase with age.

More prominent features include:

• Prognathism (protrusion of the lower jaw).

• Open mouth.

• Macroglossia.

Developmental Delay:

Speech and developmental delays are seen in all individuals. Individuals affected may have an IQ range of 30 to 60. In mild Fukuyama-type congenital muscular dystrophy, the intelligence quotient (IQ) is greater than 35; in severe forms of Fukuyama-type congenital muscular dystrophy, Iq is less than 30.

Features of an individual with maximum development with Fukuyama-type congenital muscular dystrophy include:

• Dozens of spoken words.

• Sitting without help.

• Sliding along the floor with buttocks.

In mild cases, the individual may achieve standing and walking. In severe cases, the individual may lack head control and lose the ability to sit independently.

Social Development:

The social abilities are not affected by the range as to how it affects the physical and mental abilities of an individual with Fukuyama-type congenital muscular dystrophy. In severe Fukuyama-type congenital muscular dystrophy cases, the children can maintain eye contact, make demands through vocalization, and recognize family members. Autistic features are not seen.

Seizures:

Seizures are seen in 60 % of the cases. The age of onset for febrile or afebrile seizures is 5 and 6 years, respectively.

Ocular Abnormalities:

Ocular abnormalities involve myopia and hypermetropia in 40 % to 53 % of individuals. Retinal abnormalities are observed in 32 % of the cases with more severity of Fukuyama-type congenital muscular dystrophy. Retinal dysplasia is usually focal type and mild.

Cardiac Involvement:

Slow progressive cardiac involvement is a key feature of Fukuyama-type congenital muscular dystrophy. The progression is milder than in Duchenne muscular dystrophy. Individuals with Fukuyama-type congenital muscular dystrophy may experience fibrosis in the Myocardium. Occasionally individuals have decreased left ventricular systolic function.

Swallowing Dysfunction:

Swallowing dysfunction is observed in individuals with infantile Fukuyama-type congenital muscular dystrophy, especially in severe cases and children older than ten. Failure to swallow may lead to complications such as recurrent aspiration pneumonia and death.

Neurologic Findings:

Imaging studies show cobblestone lissencephaly with cerebellar and cerebral cortical dysplasia, which is caused due to defects in neuronal migration. Infants present with severe pachygyria on the cerebral hemispheres; this feature is more evident on the frontal and temporal lobes than on the occipital and parietal lobes. Cerebellar cysts may be present under the surface of the cerebellar cortex, which contains a molecular layer and lepto meningeal tissue. Juvenile cases are focal in occipital lobes.

How Is Fukuyama-Type Congenital Muscular Dystrophy Inherited?

Risks to the family members include:

Parents of the Affected: The parents will be heterozygous, usually asymptomatic, and do not risk developing the disease.

Siblings of the Affected: The siblings have a 25 % chance of developing the disease. 50 % chance of being an asymptomatic carrier, and the remaining 25 % is neither the carrier nor asymptomatic.

Offspring of the Affected: Individuals affected by Fukuyama-type congenital muscular dystrophy have children.

Other Family Members: Each progeny of the affected individual's parents has a 50 % chance of having the disease.

What Is the Management of Fukuyama-Type Congenital Muscular Dystrophy?

There is no cure for Fukuyama-type congenital muscular dystrophy yet, but manifestations can be provided with supportive therapy. Multidisciplinary management can reduce morbidity and mortality and provide a better quality of life for individuals with Fukuyama-type congenital muscular dystrophy.

Treatments include:

• Physical activities and stretching exercises that improve mobility and prevent contractures.

• For individuals with scoliosis, spinal fusion is used for preserving breathing function and enhancing sitting balance.

• Mechanical assistance may be used, which involves long leg braces to obtain a standing posture and wheelchairs for mobility.

• Respiratory aids involve a nasal intermittent positive pressure ventilator. Usually, noninvasive ventilation is advised, particularly at night.

• Treatment of acute respiratory tract infections as they are the leading cause of death in individuals with Fukuyama-type congenital muscular dystrophy.

• Anti-seizure medications may be prescribed if indicated.

• Gastroesophageal reflux disease may be treated medically or surgically.

What Are the Evaluations Conducted After the Diagnosis?

The evaluations include:

• A neurologic evaluation may include magnetic resonance imaging (MRI) and electroencephalogram (EEG).

• Developmental assessment involves cognition, speech, and motor skills.

• Joint range of motion evaluation.

• Individuals with a lack of head control are assessed for feeding and swallowing.

• Calorie intake and nutrition assessment.

• Genetic counseling.

Conclusion

Fukuyama-type congenital muscular dystrophy is characterized by symmetric muscle weakness, hypotonia, and central nervous system disturbances. Treatment focuses on manifestations. Families affected are advised to undergo genetic counseling.