Nemaline myopathy (NM) encompasses a large spectrum of congenital myopathies characterized by hypotonia, weakness and depressed or absent deep tendon reflexes, with pathologic evidence of nemaline bodies (rods) on muscle biopsy.
Annual incidence has been estimated at 1/50,000 live births in a Finnish study but the disease is more common in the Amish community.
The age of onset varies from birth to adulthood. The main clinical manifestations include weakness (usually most severe in the face, the neck flexors and the proximal limb muscles), hypotonia and depressed or absent deep tendon reflexes. Facial weakness may lead to sucking, swallowing and speech difficulties. Respiratory muscles are frequently involved. NM is divided into 6 clinically overlapping subtypes depending on the age at onset and the severity of motor and respiratory involvement. Typical NM (approximately 50% of patients, see this term) is a moderate form of the disease with onset in the neonatal period. Most patients are able to live an independent, active life. Severe congenital NM (10-20% of patients; see this term) is characterized by severe hypotonia and little spontaneous movement. Survival after infancy is rare. Intermediate NM (20% of patients; see this term) is characterized by slow achievement of gross motor milestones, and loss of ambulation and/or independent respiration by age 11 years. Adult-onset NM is usually sporadic (<5% of patients; see this term). Onset is between 20 and 50 years of age. This form is characterized by rapid progression. Mild NM or childhood onset NM (10-15% of patients; see these terms) is characterized by the development of symmetric weakness of ankle dorsiflexion and foot drop around 10 years of age. Weakness is slowly progressive. An Amish NM (see this term) has been observed in several families. It has a neonatal onset and life expectancy rarely exceeds 2 years.
Seven genes involved in muscle thin filament structure and function, have been linked to NM: NEB (2q22), TPM2 (9p13), TPM3 (1q21.2), ACTA1 (1q42.13), TNNT1 (19q13.4), CFL2 (14q12) and KBTBD13 (15q22.31). Clear genotype/phenotype correlations have not been established.
Diagnosis is based on clinical examination and histopathological findings on muscle biopsy, which may reveal a change in fiber type proportion and size and, if combined with the Gomori trichrome staining method, show rod-shaped structures (nemaline bodies) in the sarcolemma and more rarely in the nucleus. Muscle imaging studies such as ultrasonography, computed tomography or magnetic resonance imaging (MRI), may help selecting muscles to biopsy and can guide genetic testing. Muscle enzymes are generally normal or mildly increased. Molecular genetic testing may confirm the diagnosis.
The differential diagnosis includes other neuromuscular diseases displaying nemaline bodies: dermatomyositis, myotonic dystrophy type 1 and mitochondrial myopathy.
Antenatal diagnosis is feasible since genetic tests are available to detect mutations in ACTA1, NEB, TPM3, TPM2,TNNT1, CFL2 and KBTBD13. It requires prior identification of the familial causative mutation(s).
A multidisciplinary approach is needed to handle respiratory insufficiency (permanent or intermittent use of mechanical ventilation and treatment of lower respiratory tract infections) and feeding difficulties (feeding techniques and calorie-enriched diets). Scoliosis, joint contractures or speech anomalies must be managed as usual. Cardiac function must be monitored.
Prognosis depends on the NM type, and life expectancy ranges from few months to a near-normal lifespan.
Last update: October 2011