Nemaline Myopathy

Nemaline myopathy is a genetically diverse congenital myopathy with rod shaped inclusions (nemaline bodies) in muscle fibres. Prevalence is about 1 in 50,000 live births. Causative genes include NEB (most common, recessive), ACTA1 (dominant and de novo), TPM2, TPM3, TNNT1 and CFL2.

Pathophysiology. Variants in thin filament proteins impair sarcomere assembly and force generation.

Severe neonatal form: hypotonia, respiratory failure, feeding difficulty and arthrogryposis, often fatal in infancy. Typical congenital form: hypotonia, facial and axial weakness, high arched palate, slow motor milestones, scoliosis and respiratory insufficiency. Childhood and adult onset forms present with milder proximal weakness, foot drop or cardiomyopathy. Facial weakness gives an elongated face.

Red flags.

• Respiratory failure and aspiration.
• Hypoventilation during sleep.

Creatine kinase is normal or mildly raised. Muscle biopsy shows nemaline rods (Gomori trichrome) and type 1 fibre predominance. Muscle MRI shows distinctive fatty replacement. Genetic testing with a congenital myopathy panel or exome sequencing is the key test. Assess respiratory function, sleep study, echocardiography and swallowing.

Differential diagnosis.

• Other congenital myopathies (core, centronuclear), congenital muscular dystrophies.
• Spinal muscular atrophy, congenital myasthenic syndromes and Pompe disease.
• Congenital myotonic dystrophy.

No cure exists. Care is multidisciplinary.

Respiratory care. Monitor forced vital capacity and overnight oximetry, offer non-invasive ventilation for hypoventilation, airway clearance (cough assist), and treat chest infections early. Vaccinate against influenza, pneumococcus and respiratory syncytial virus where available.

Feeding and nutrition. Speech and swallowing therapy, gastrostomy for unsafe swallow, and dietitian support.

Orthopaedic. Physiotherapy, orthoses and scoliosis monitoring, with spinal surgery in selected patients.

Cardiac. Echocardiography if respiratory or cardiac involvement is suspected, especially in ACTA1 disease.

Anaesthesia. Prior planning, with caution for respiratory depression. Malignant hyperthermia risk is not clearly raised.

Monitoring. Respiratory function every 6 to 12 months, scoliosis and growth.

Referral and escalation. Refer to paediatric neuromuscular and respiratory services and genetics.

Special groups. In pregnancy, assess respiratory reserve.