Nemaline myopathy (NM) comprises a set of myopathic disorders characterized by hypotonia, weakness, and absent or decreased deep tendon reflexes.
NM is considered a rare disease because of its low prevalence. A Finnish study and other recent research conducted in the U.S. Ashkenazi Jewish population, estimated an incidence of 1:50,000 live births. However, there seems to be ethnic segregation, being more common in the Amish community (1:500).
Muscle weakness is seen most severe in the neck flexors, facial and proximal limb muscles.
NM has been classified into six types according to the time of onset and severity of respiratory and motor complications.
The most common is congenital nemaline myopathy, which is associated with mutations in the gene ACTA1 and appears in 46% of cases. NM intermediate is characterized by a delay in the acquisition of basic motor skills. NM severe congenital affects 16% of all individuals with NM, and it is characterized by hypotonia and the inability to perform spontaneous movements.
Adult onset NM can occur sporadically (4%), arising from 20-50 years old. NM childhood-onset (13%) is characterized by progressive weakness, affecting ankle dorsiflexion. The symptom of foot drop is observed around 10 years old. Weakness is slowly progressive. Amish type NM appears in newborns and it has a life expectancy of no more than two years.
Genetic diagnosis is useful for the detection of the disease. Pathology is associated with mutations in 7 different genes: ACTA1 (1q42.13), NEB (2q22), TNNT1 (19q13.4), TPM2 (9p13), TPM3 (1q21.2), KBTBD13 (15q22.31) and CFL2 (14q12). Alterations can be inherited in an autosomal recessive, autosomal dominant or arise spontaneously.
Bioarray has a NGS panel for full sequencing of the genes associated with disease.