Limb-girdle muscular dystrophy
Limb-girdle muscular dystrophy is an inherited, slowly progressive dystrophy of the shoulder and pelvic girdle muscles caused by mutations in sarcolemmal and excitation-contraction coupling proteins such as caveolin and dysferlin. It is confirmed by genetic testing after an elevated creatine kinase and a myopathic EMG, and care centers on respiratory and cardiac surveillance, noninvasive ventilation once daytime hypercapnia appears, heart failure therapy for cardiomyopathy, and avoidance of succinylcholine.
- Topic reviewThe full article, organized the way the exam asks it.
- ABIM-format MCQsVignettes with an explanation for every wrong answer.
- Key factsThe numbers and thresholds worth memorizing, up front.
- AI tutorMedBrain answers the question you're stuck on.
What this article covers
- Overview
Definition: limb-girdle muscular dystrophy is an inherited muscular dystrophy, a progressive, genetically mediated myopathy with muscle tissue destruction, that produces weakness of the shoulder and…
- Epidemiology
Age at onset: onset is variable, from young childhood (where it can mimic Duchenne muscular dystrophy, including calf pseudohypertrophy) through adulthood.
- Risk factors
Pathogenic variant in a sarcolemmal or coupling gene: a mutation in a gene such as caveolin or dysferlin is the defining and necessary cause.
- Pathophysiology
Defective membrane and coupling proteins: mutant caveolin, dysferlin, and related proteins destabilize the sarcolemma and disrupt the transverse-tubule network.
- Clinical features
Symmetric proximal girdle weakness: the hallmark is weakness of the shoulder and pelvic girdles, legs more than arms, with neck flexor weakness and difficulty rising from a chair or raising the arms overhead.
- Differential diagnosis
Polymyositis and dermatomyositis: acute to subacute symmetric proximal weakness with a highly elevated creatine kinase, a pathognomonic rash in dermatomyositis, and inflammation on biopsy that responds to prednisone.
- Diagnosis
Basis of diagnosis: there is no clinical criteria set; the diagnosis is confirmed by genetic testing that identifies a pathogenic variant in a limb-girdle dystrophy gene (such as caveolin or…
- Management
First step, baseline respiratory and cardiac assessment: at diagnosis, obtain pulmonary function tests and an ECG with echocardiography; there is no disease-modifying drug, so care is organized around these two organ systems.
- Complications
Chronic hypercapnic respiratory failure: respiratory muscle weakness causes nocturnal hypoventilation that progresses to daytime hypercapnia.
- Prognosis
Slow course: progression is slow, measured in years, which separates it from the fulminant course of Duchenne muscular dystrophy.
- Prevention
No primary prevention: the disease is genetic; prevention means genetic counseling of the family and early detection of complications.
Read the whole article
Subscribing to Internal Medicine opens every article, the full question bank and MedBrain, on the web, iPhone and Android.
Related articles
- Becker muscular dystrophy
Becker muscular dystrophy is a milder, later-onset X-linked dystrophinopathy causing progressive proximal weakness and dilated cardiomyopathy from partially functional dystrophin. Diagnosis rests on elevated creatine kinase and confirmatory dystrophin genetic testing, and management centers on cardiac surveillance with ACE-inhibitor and beta-blocker therapy, physical therapy, and genetic counseling rather than the glucocorticoid regimen used in Duchenne muscular dystrophy.
- Duchenne muscular dystrophy
Duchenne muscular dystrophy is an X-linked recessive dystrophinopathy from absent dystrophin, causing early-onset, fulminant proximal weakness with loss of independent ambulation by the early teens and progressive cardiomyopathy. Diagnosis is by genetic testing for a DMD gene deletion/duplication; management is glucocorticoid therapy plus multidisciplinary cardiac, respiratory, and orthopedic surveillance.
- Myotonic dystrophy
Myotonic dystrophy is an autosomal dominant trinucleotide repeat disorder causing myotonia, progressive distal muscle weakness, and multisystem involvement including cataracts, cardiac conduction disease, and endocrinopathy. Diagnosis is clinical, confirmed by genetic testing for the DMPK (type 1) or CNBP (type 2) repeat expansion; management is multidisciplinary, with mexiletine for myotonia and mandatory cardiac screening given the risk of sudden death.
- Polymyositis
Polymyositis is an idiopathic inflammatory myopathy causing symmetric, subacute proximal muscle weakness with no rash, driven by endomysial CD8-positive T-cell invasion of non-necrotic, MHC class I-expressing muscle fibers. It is a diagnosis of exclusion confirmed by muscle biopsy, and first-line treatment is high-dose prednisone with a steroid-sparing agent such as methotrexate or azathioprine started concurrently.
- Inclusion body myositis
Inclusion body myositis is a sporadic inflammatory myopathy of older adults that breaks the pattern of the other myositides: it favors men, causes insidious, often asymmetric weakness of the finger flexors and quadriceps plus dysphagia, and raises creatine kinase only mildly. Biopsy shows endomysial inflammation with rimmed vacuoles and congophilic amyloid inclusions. It does not respond to glucocorticoids or immunosuppression, so treatment centers on structured exercise and physical therapy, dysphagia evaluation and swallowing therapy, and falls prevention.
- Drug-induced myopathy
Drug-induced myopathy spans a spectrum from asymptomatic creatine kinase elevation to rhabdomyolysis and is caused by statins (most common), glucocorticoids, colchicine, hydroxychloroquine, zidovudine, amiodarone, alcohol, and cocaine, each with a distinct mechanism, time course, and presentation. The critical distinction is toxic myopathy that resolves with drug withdrawal versus statin-associated anti-HMGCR necrotizing myopathy, which persists after discontinuation and requires immunosuppression.
- Dilated cardiomyopathy
Dilated cardiomyopathy is left ventricular (often biventricular) dilation with systolic dysfunction not explained by loading conditions or coronary disease, from genetic, viral, toxic, or peripartum causes, presenting as heart failure with reduced ejection fraction. Diagnosis is by echocardiography with a workup for reversible causes, and treatment is guideline-directed heart-failure therapy with device therapy for high-risk patients.