Nelson Textbook of Pediatrics 22nd Edition — Myasthenia gravis (autoimmune AChR/MuSK), congenital myasthenic syndromes (CMS), infantile botulism, spinal muscular atrophy (SMA, SMN1, nusinersen, risdiplam, Zolgensma), SMA-plus syndromes, SMARD1 (IGHMBP2), Brown-Vialetto-Van Laere (riboflavin transporter SLC52A2/A3).
🌐 paeds.online — Pakistan's Pediatric Platform| Disorder | Mechanism | Key Features | Diagnosis | Treatment |
|---|---|---|---|---|
| Autoimmune myasthenia gravis (MG) | Anti-AChR (70-80%) or MuSK antibodies | Fatigable ptosis, diplopia, bulbar weakness, proximal weakness | AChR/MuSK antibodies, RNS decrement | Pyridostigmine, prednisone, IVIG, thymectomy |
| Transient neonatal myasthenia | Maternal AChR antibodies | Hypotonia, poor feeding, respiratory distress in first 1-3 days, resolves by 2 months | Mother with MG, response to pyridostigmine | Supportive, pyridostigmine short-term |
| Congenital myasthenic syndromes (CMS) | Genetic (CHRNE, RAPSN, DOK7, COLQ, etc.) | Onset birth/early childhood, ptosis, ophthalmoparesis, episodic apnea (CHAT, RAPSN) | Genetic testing, RNS decrement | Pyridostigmine (some), ephedrine/salbutamol (DOK7), avoid AChE inhibitors (COLQ, slow-channel) |
| Infantile botulism | C. botulinum toxin (cleaves SNARE proteins) | Constipation, weak cry, ptosis, descending paralysis, dilated pupils | Stool toxin, EMG incremental response | Botulism immune globulin (BabyBIG), supportive |
| Tick paralysis | Neurotoxin from wood/dog tick | Ascending paralysis, areflexia, sensory symptoms | Find tick, remove | Tick removal, supportive |
| Disorder | Gene | Key Features | Treatment |
|---|---|---|---|
| SMA type 1 (Werdnig-Hoffmann) | SMN1 deletion (5q) | Onset <6 mo, severe hypotonia, areflexia, tongue fasciculations, never sit, respiratory failure | Nusinersen, risdiplam, Zolgensma (gene therapy) |
| SMA type 2 | SMN1 deletion | Onset 6-18 mo, sit independently, never walk, scoliosis | Nusinersen, risdiplam |
| SMA type 3 (Kugelberg-Welander) | SMN1 deletion | Onset >18 mo, walk independently, slowly progressive | Nusinersen, risdiplam |
| SMARD1 | IGHMBP2 | Distal weakness, diaphragmatic palsy, respiratory failure, onset 6w-6mo | Supportive ventilation, genetic counseling |
| Brown-Vialetto-Van Laere (BVVL) | SLC52A2/A3 (riboflavin transporter) | Sensorineural deafness, bulbar palsy, facial weakness, respiratory insufficiency, optic atrophy | High-dose riboflavin (10-50 mg/kg/day) |
| Fazio-Londe syndrome | SLC52A2/A3 (same as BVVL without deafness) | Progressive bulbar palsy without deafness | High-dose riboflavin |
| PCH type 1 (pontocerebellar hypoplasia) | EXOSC3, VRK1, TSEN54 | SMA + cerebellar hypoplasia, microcephaly, seizures | Supportive |
Nusinersen (Spinraza): Intrathecal ASO, promotes SMN2 exon 7 inclusion. All SMA types. Loading doses then q4mo maintenance.
Risdiplam (Evrysdi): Oral small molecule splice modifier. For SMA ≥2 months. Increases SMN2 exon 7 inclusion.
Onasemnogene abeparvovec (Zolgensma): IV gene therapy (AAV9) delivering SMN1. For SMA <2 years (≤21 kg). One-time dose.
Brown-Vialetto-Van Laere: Riboflavin transporter deficiency — treatable! High-dose riboflavin (10-50 mg/kg/day).