Congenital neuromuscular disorders are a group of genetic diseases affecting nerves, muscles, and neuromuscular junctions (eg, congenital myopathies, congenital muscular dystrophies, congenital myasthenic syndromes, and congenital myotonic dystrophy).
ESSENTIALS OF DIAGNOSIS AND TYPICAL FEATURES
A heterogeneous group of early-onset muscle diseases
Characteristic myopathic findings on muscle biopsy
Clinically present with hypotonia and muscle weakness at birth or in infancy
Mutations in a heterogeneous group of genes have been identified
The congenital myopathies are a rare, heterogeneous group of hereditary genetic muscle diseases that are defined by architectural abnormalities in the muscle fibers. Besides the clinical features, muscle biopsy and genetic analyses are essential in the diagnosis. Based on the findings on muscle biopsy, congenital myopathies can be further classified into core myopathies, nemaline myopathies, centronuclear myopathies, congenital fiber-type disproportion myopathies, and myosin storage myopathies. Management is provided by a multidisciplinary neuromuscular team. To date, only supportive treatment is available.
Patients present with similar symptoms, with either a floppy infant at birth or later with muscle weakness. Polyhydramnios due to decreased swallowing function and reduced fetal movements in utero can be seen in patients with prenatal onset. Other clinical presentations include muscle weakness, delayed motor development milestones, respiratory insufficiency, feeding difficulties, and arthrogryposis. Severe infantile presentations are associated with marked weakness and may lead to death from respiratory failure in early life, whereas other affected children mostly have a relatively benign course with static weakness and hypotonia. Deep tendon reflexes are usually depressed or absent.
Serum creatine kinase (CK) levels may be normal or mildly elevated. Electromyography (EMG) is usually normal but may show mild and nonspecific myopathic features. Nerve conduction studies (NCSs) are normal. Histologically, muscle biopsy findings in most congenital myopathies demonstrate type 1 myofiber predominance and atrophy with superimposed characteristic morphologic features most commonly including nemaline body, central core, central nucleation, and multiple minicores. In addition to muscle biopsy, genetic testing that demonstrates mutations in causative genes will further aid in establishing the diagnosis.
Differential diagnoses include broad categories such as congenital muscular dystrophy, congenital myotonic dystrophy, congenital myasthenic syndrome, infantile-onset motor neuron diseases, and metabolic myopathy.
Feeding intolerance, respiratory deficiency, neuromuscular scoliosis, hip joint subluxations, and arthrogryposis are common complications. Cardiomyopathies can also be complications in some patients.
Supportive treatment managed through several medical disciplines is provided typically through a multidisciplinary pediatric neuromuscular care center. The management is typically orchestrated by a pediatric neurologist, in collaboration with other specialties, including cardiology, pulmonary, dietary, gastroenterology, orthopedics, genetics, rehabilitation medicine, physical therapy, occupational therapy, and speech therapy.