Limb-girdle muscular dystrophy (LGMD)

The limb-girdle muscular dystrophies present with symmetric weakness and wasting of the pelvic and shoulder girdle muscles, accompanied by elevated serum creatine kinase and dystrophic features on muscle biopsy. Disease onset ranges from early childhood to late adulthood with substantial clinical variability across subtypes. Initial manifestation typically include hip and proximal leg weakness, difficulty climbing stairs a waddling gait, and a positive Gowers’ sign, while early motor and intellectual development is usually normal. Additional features may include scapular winging, scoliosis, Achilles tendon and other joint contractures, hypertrophy of the calf, deltoid, or quadriceps muscles. Cardiac involvement, including dilated or hypertrophic cardiomyopathy and arrhythmias, occurs in several LGMD subtypes, and respiratory muscle weakness with nocturnal hypoventilation may develop during disease progression. Autosomal recessive forms generally present earlier and are associated with more severe respiratory involvement, whereas autosomal dominant forms typically present in adolescence or adulthood with slower disease progression and relatively preserved ambulation.

The estimated prevalence ranges from 0.8 to 6 per 100,000.

Several genes are associated with limb-girdle muscular dystrophies, grouped into autosomal recessive (LGMD R) and autosomal dominant (LGMD D) subtypes. The most common cause is calpainopathy (CAPN3-related LGMD R1). Other recessive forms include dysferlinopathy (DYSF, LGMD R2) and anoctaminopathy (ANO5, LGMD R12); dominant forms include DNAJB6-related LGMD D1 and TNPO3-related LGMD D2.

The genetic conditions associated with limb-girdle muscular dystrophies include both autosomal recessive forms (LGMD R) and autosomal dominant forms (LGMD D).

• Where limb-girdle muscular dystrophy is suspected to have a genetic cause, molecular genetic testing can identify the underlying condition and confirm a clinical suspicion.
• The identified entity guides further clinical management and is a prerequisite for targeted medical care; therapeutic options are evaluated individually by the treating physicians.
• Identification of the underlying pathogenic germline variant enables predictive testing of at-risk family members and provides information relevant to family planning.

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• Georganopoulou DG, Moisiadis VG, Malik FA, Mohajer A, Dashevsky TM, Wuu ST, et al. A Journey with LGMD: From Protein Abnormalities to Patient Impact. The protein journal. 2021;40(4):466-488. doi: 10.1007/s10930-021-10006-9. PMID: . PMCID: PMC8190568.
• Bouchard C, Tremblay JP, Limb-Girdle Muscular Dystrophies Classification and Therapies. J Clin Med. 2023;12(14):4769. Doi: 10.3390/jcm12144769. PMID: . PMCID: PMC10381329.