Nelson Textbook of Pediatrics 22nd Edition โ Duchenne MD (Xp21 dystrophin), Becker MD, myotonic dystrophy (CTG repeat), Emery-Dreifuss (LMNA/emerin), limb-girdle MD, facioscapulohumeral MD (D4Z4 contraction), congenital MD. Genetic diagnosis, corticosteroids, exon skipping, gene therapy, cardiac surveillance.
๐ paeds.online โ Pakistan's Pediatric Platform| Disorder | Gene / Locus | Inheritance | Protein | Key Features | CK |
|---|---|---|---|---|---|
| Duchenne MD | DMD (Xp21) | XR | Dystrophin (absent) | Proximal weakness, calf hypertrophy, Gowers sign, loss of ambulation ~12y, cardiomyopathy, intellectual impairment | Very high (15,000-35,000) |
| Becker MD | DMD (Xp21) | XR | Dystrophin (reduced/abnormal) | Milder, onset >5-7y, ambulatory into adulthood, cardiomyopathy, cramps | High (1,000-15,000) |
| Myotonic dystrophy type 1 (DM1) | DMPK (19q13) CTG repeat | AD | DMPK (RNA toxicity) | Distal weakness, myotonia, cataracts, cardiac conduction defects, intellectual impairment, anticipation | Normal-mild elevation |
| Emery-Dreifuss MD | EMD (Xq28) or LMNA (1q21) | XR, AD | Emerin, lamin A/C | Early contractures (elbows, neck), humeroperoneal weakness, life-threatening cardiac arrhythmias (atrial standstill, VT) | Mild-moderate |
| Facioscapulohumeral MD (FSHD) | D4Z4 contraction (4q35) | AD | DUX4 derepression | Facial weakness (horizontal smile), scapular winging, asymmetric weakness, retinal vasculopathy, hearing loss | Normal-elevated |
| Limb-girdle MD (LGMD) | >30 genes (CAPN3, DYSF, SGCA-SGCG, FKRP, ANO5, etc.) | AD/AR | Various (calpain, dysferlin, sarcoglycans, etc.) | Proximal limb-girdle weakness, variable progression, cardiomyopathy in some | Normal-very high |
| Congenital MD (CMD) | LAMA2, COL6A1-3, FKRP, FKTN, POMT1, etc. | AR | Merosin, collagen VI, glycosylation enzymes | Severe hypotonia at birth, contractures, brain malformations (dystroglycanopathies), white matter changes (LAMA2) | Elevated |
Corticosteroids: Prednisone 0.75 mg/kg/day or deflazacort 0.9 mg/kg/day โ prolong ambulation, slow scoliosis, preserve pulmonary function.
Exon skipping: Eteplirsen (exon 51), golodirsen (exon 53), viltolarsen (exon 53) โ ~13% and ~8% of DMD patients.
Gene therapy: Elevidys (delandistrogene moxeparvovec) โ AAV-delivered micro-dystrophin for children 4-5 years old.
Ataluren: Readthrough for nonsense mutations (10-15% of DMD).