Nelson Textbook of Pediatrics 22nd Edition — Heterogeneous group of >30 genes. LGMD2 (AR) more common than LGMD1 (AD). Key forms: sarcoglycanopathies (LGMD2C-2F, Duchenne-like), calpainopathy (CAPN3, LGMD2A), dysferlinopathy (DYSF, LGMD2B/Miyoshi), FKRP (LGMD2I, cardiomyopathy), anoctaminopathy (ANO5, LGMD2L). Proximal limb-girdle weakness, variable CK, muscle biopsy for protein defects.
🌐 paeds.online — Pakistan's Pediatric Platform| LGMD Type | Gene | Protein | Inheritance | Key Features | CK | Cardiac |
|---|---|---|---|---|---|---|
| LGMD2A (R1) | CAPN3 | Calpain-3 | AR | Onset 8-15y, scapular winging, variable progression | Very high | Sparred |
| LGMD2B (R2) | DYSF | Dysferlin | AR | Adolescent/young adult; LGMD or Miyoshi myopathy (calf weakness) | Very high | Sparred |
| LGMD2C (R5) | SGCG | γ-Sarcoglycan | AR | Duchenne-like, onset 4-7y, loss of ambulation teenage | Very high | + |
| LGMD2D (R3) | SGCA | α-Sarcoglycan (adhalin) | AR | Onset 2-15y, quadriceps weakness, Duchenne-like | Very high | Rare |
| LGMD2E (R4) | SGCB | β-Sarcoglycan | AR | Onset first decade, loss of ambulation 10-25y | Very high | Occasional |
| LGMD2F (R6) | SGCD | δ-Sarcoglycan | AR | Onset 2-10y, dilated cardiomyopathy, loss of ambulation 1st-2nd decade | Very high | Dilated CM |
| LGMD2I (R9) | FKRP | Fukutin-related protein | AR | Variable (CMD to LGMD), cardiomyopathy common, muscle cramps | High | Common |
| LGMD2L (R12) | ANO5 | Anoctamin-5 | AR | Northern European, onset 2nd-3rd decade, LGMD or Miyoshi phenotype, PVCs reported | High | Rare (PVCs) |
| LGMD1B | LMNA | Lamin A/C | AD | Contractures, axial weakness, cardiac arrhythmias (life-threatening) | Normal-mild | High risk |
Step 1: Clinical: proximal limb-girdle weakness (hip and shoulder girdles), usually symmetric. CK often elevated (varies by subtype).
Step 2: Muscle biopsy: dystrophic changes. Immunohistochemistry for sarcoglycans, dysferlin, calpain-3, dystrophin, merosin, α-dystroglycan.
Step 3: Genetic testing: targeted panels for known LGMD genes (CAPN3, DYSF, SGCA-SGCG, FKRP, ANO5, LMNA, etc.) or whole exome sequencing.
Step 4: Cardiac evaluation: ECG/echo in all LGMD patients (especially FKRP, sarcoglycanopathies, LMNA).