A neonate is born floppy with weak cry, poor feeding, and respiratory distress requiring ventilatory support. Facial weakness is prominent (myopathic face, tented upper lip). Muscle biopsy shows characteristic rod-shaped inclusions ("nemaline bodies") on Gomori trichrome stain. CK is normal or only mildly elevated.
Genetically heterogeneous; multiple genes encoding thin-filament proteins of skeletal muscle. The most common:
| Gene | Inheritance | Notes |
|---|---|---|
| NEB (nebulin) | AR | Most common; typically classic/severe forms |
| ACTA1 | AD (de novo) > AR | Severe and intermediate forms; many de novo |
| TPM2, TPM3 | AD/AR | Variable severity |
| TNNT1 | AR | Amish form |
| CFL2 | AR | Rare, severe |
Disease severity correlates loosely with gene and mutation type. About a third of cases lack a molecular diagnosis.
- Hypotonia and weakness, prominent facial and bulbar (feeding/speech) involvement
- Respiratory weakness is often severe and can be the dominant clinical issue, sometimes out of proportion to limb weakness (diaphragmatic and intercostal involvement)
- Normal-to-mildly elevated CK (contrasts with muscular dystrophies, where CK is markedly elevated)
- Slow progression in most subtypes; some forms are static or even mildly improving
- Cognition normal
Severity ranges from severe congenital (neonatal lethal without ventilation) to childhood/adult-onset mild forms.
- Muscle biopsy: nemaline rods on Gomori trichrome (red rods on blue-green background); rods are sub-sarcolemmal aggregates of α-actinin and thin-filament proteins
- EMG: myopathic pattern
- Genetic testing: multigene panel for congenital myopathies; NEB sequencing is technically demanding (huge gene)
- Pulmonary function testing (sitting + supine) crucial for management
- Congenital muscular dystrophies (CMD): high CK, muscle fibrosis on biopsy; biopsy distinguishes
- Spinal muscular atrophy (SMA): denervation pattern on EMG, SMN1 deletion
- Myotubular myopathy (X-linked, MTM1): central nuclei, severe respiratory failure in male infants
- Central core disease: RYR1, central cores on biopsy, malignant hyperthermia susceptibility
- Congenital myasthenic syndromes: fatigability, decremental EMG response, CHRNE/etc.
- Respiratory: non-invasive ventilation (BiPAP) often needed nocturnally; tracheostomy in severe cases. Pulmonary follow-up is the lifeline.
- Feeding: G-tube common in severe forms
- PT/OT: range of motion, contracture prevention
- Cardiac: generally not affected (unlike muscular dystrophies)
- Anesthesia: caution; succinylcholine and depolarizing agents avoided; some forms have malignant hyperthermia susceptibility (RYR1-overlap)
"Nemaline = thread-like rods on biopsy" (from Greek nēma = thread). Combined with normal CK and prominent facial/respiratory weakness, the biopsy + clinical picture is unmistakable.
"Floppy baby + nemaline rods + normal CK": the three-feature trio that points to the diagnosis in most clinical scenarios.