Nelson Textbook of Pediatrics 22nd Edition — X-linked recessive (MTM1), severe congenital hypotonia, ptosis, ophthalmoplegia, respiratory failure, undescended testes. Muscle biopsy: central nuclei in >90% of fibers. Gene therapy in human trials.
🌐 paeds.online — Pakistan's Pediatric Platform| Gene | Inheritance | Protein | Clinical Features | Prognosis |
|---|---|---|---|---|
| MTM1 | X-linked recessive | Myotubularin | Severe neonatal hypotonia, ptosis, ophthalmoplegia, respiratory failure, undescended testes | ~75% die in first months; survivors severe disability |
| DNM2 | AD / sporadic | Dynamin 2 | Milder, later onset (childhood to adult), slowly progressive, pseudohypertrophy | Better prognosis, often ambulatory |
| BIN1 | AR | Amphiphysin 2 | Early or late onset, variable ophthalmoplegia | Variable |
| RYR1 | AR / sporadic | Ryanodine receptor | Centronuclear pattern with cores, MH risk | Variable |
| TTN | AR | Titin | Centronuclear myopathy with cardiomyopathy | Poor if cardiac involved |
Loss of myotubularin → defective T-tubule & sarcoplasmic reticulum organization → abnormal excitation-contraction coupling. MTM1, dynamin-2, and amphiphysin all localize to T-tubule wall in triads.
X-linked MTM1 accounts for ~80% of severe congenital cases. Female carriers may be symptomatic due to skewed X-inactivation.