Limb Girdle Muscular Dystrophy

Limb girdle muscular dystrophies (LGMD) are genetically heterogeneous dystrophies with progressive proximal weakness of shoulder and pelvic girdle.

• Nomenclature: LGMD D (dominant) and R (recessive) with numbers, over 30 genes: CAPN3 (R1, commonest), DYSF (R2), sarcoglycans (R3 to R6), FKRP (R9), ANO5 (R12), LMNA (D?), TTN.

• Prevalence about 1 in 15,000.

• Cardiac involvement in sarcoglycanopathies, FKRP, LMNA (conduction disease, cardiomyopathy); respiratory in FKRP, sarcoglycan.

• Progressive symmetrical proximal weakness, waddling gait, scapular winging, difficulty climbing stairs.

• Calf hypertrophy (sarcoglycanopathy, FKRP), contractures.

• Dysferlinopathy: distal calf weakness, onset in 20s, markedly high CK.

• Cardiomyopathy, arrhythmia, respiratory failure.

• CK elevated (variable, over 10 times in dysferlinopathy).

• Next generation sequencing myopathy panel or exome (preferred first line).

• Muscle biopsy with immunohistochemistry/Western blot (dystrophin, sarcoglycan, dysferlin, calpain) if genetics unrevealing.

• Muscle MRI patterns; ECG, Holter, echocardiogram, spirometry.

• Exclude inflammatory myopathy, Pompe disease, FSHD, metabolic myopathy, acquired myopathy.

• Mostly supportive: physiotherapy, orthoses, stretching, mobility aids.

• Cardiac: annual ECG and echocardiogram; ACE inhibitor, beta blocker for cardiomyopathy; pacemaker or ICD for LMNA and conduction disease.

• Respiratory: spirometry annually, non invasive ventilation for hypoventilation, cough assist.

• Glucocorticoids are not helpful in most (may be harmful in dysferlinopathy).

• Gene therapy (SGCB, LGMD2E, delandistrogene) in trials.

• Genetic counselling.