Muscular Dystrophy — Symptoms, Causes & Treatment | MyMedicPlus

Muscular dystrophy (MD) is a heterogeneous group of over 30 hereditary genetic diseases characterised by progressive muscle weakness and wasting due to mutations affecting structural and functional muscle proteins. The underlying defect causes ongoing degeneration of skeletal muscle fibres with incomplete regeneration, leading to replacement of muscle tissue with fibrous and fatty tissue. Duchenne muscular dystrophy (DMD) is the most severe and most common childhood-onset form, affecting approximately 1 in 3,500 male births globally and arising from mutations in the DMD gene that abolish dystrophin production — resulting in rapid muscle degeneration from early childhood. Becker muscular dystrophy (BMD) is a milder allelic variant with partial dystrophin production. Myotonic dystrophy (DM1 and DM2) is the most prevalent adult-onset form, characterised by multisystem involvement beyond muscle. Other types include limb-girdle muscular dystrophy (LGMD), facioscapulohumeral muscular dystrophy (FSHD), Emery-Dreifuss MD, oculopharyngeal MD, and congenital MDs. The clinical course, severity, inheritance pattern, organs affected, and life expectancy vary substantially between subtypes, making genetic diagnosis essential for prognosis and treatment planning.

All forms of muscular dystrophy are caused by mutations in genes encoding proteins essential for muscle structure, membrane stability, or function. Duchenne and Becker MD: mutations in the DMD gene on the X chromosome (Xp21), encoding the rod-shaped cytoskeletal protein dystrophin which links the intracellular cytoskeleton to the extracellular matrix — providing mechanical stability to muscle fibres during contraction. In DMD, out-of-frame deletions, duplications, or point mutations abolish dystrophin production entirely; in BMD, in-frame mutations allow production of a truncated, partially functional dystrophin. DMD/BMD is X-linked recessive — affecting males almost exclusively; female carriers have a 50% chance of an affected son. Approximately one-third of DMD cases arise from de novo mutations with no family history. Myotonic dystrophy type 1 (DM1): caused by expansion of CTG trinucleotide repeats in the 3' untranslated region of the DMPK gene (chromosome 19q13); DM2: CCTG repeat expansion in the CNBP gene (chromosome 3q21). Both are autosomal dominant with genetic anticipation (worsening of disease in successive generations due to further repeat expansion). Facioscapulohumeral MD (FSHD): deletion of the D4Z4 repeat region on chromosome 4q35, causing aberrant expression of the DUX4 transcription factor in muscle. Emery-Dreifuss MD: mutations in EMD (emerin) or LMNA (lamin A/C) genes affecting nuclear envelope integrity. Genetic counselling and mutation analysis guide family planning and prenatal testing.

Clinical manifestations differ by MD subtype. Duchenne MD: presents in boys aged 2-5 years with delayed motor milestones, frequent falls, difficulty running, climbing stairs, or rising from the floor. Classic signs include Gowers' manoeuvre (using hands to climb up the thighs when rising from a seated floor position — indicating proximal hip and limb girdle weakness), waddling gait (positive Trendelenburg sign), toe walking (equinus gait), pseudohypertrophy of the calf muscles (replacement of muscle by fat and connective tissue gives a deceptively enlarged appearance), and lumbar lordosis. Progressive proximal muscle weakness leads to loss of independent ambulation by age 10-12 years. Cardiomyopathy (dilated) develops in virtually all DMD patients from adolescence — causing heart failure and arrhythmias. Respiratory failure from progressive intercostal and diaphragmatic muscle weakness is the leading cause of death. Cognitive and behavioural difficulties (ADHD, ASD, anxiety) occur in approximately one-third of DMD patients due to dystrophin isoforms in the brain. Becker MD: similar but milder presentation, with preserved ambulation into adulthood; cardiomyopathy may be more prominent than skeletal muscle weakness. Myotonic dystrophy (DM1): myotonia (sustained, difficulty relaxing grip after handshake — demonstrated clinically by percussion of the thenar eminence), distal limb weakness (in contrast to DMD's proximal weakness), facial muscle weakness (ptosis, dysarthria, dysphagia), cataracts (slit-lamp visible by fourth decade in virtually all), cardiac conduction defects (bradycardia, heart block — risk of sudden death), and multi-system involvement including endocrine (diabetes, hypogonadism), CNS (hypersomnolence, cognitive), and respiratory problems. Facioscapulohumeral MD: slowly progressive weakness of facial muscles (inability to close eyes fully, difficulty smiling), shoulder girdle (scapular winging), and upper arms — asymmetric pattern is characteristic.

Serum creatine kinase (CK) is markedly elevated in DMD — typically 10-100x the upper limit of normal at diagnosis (often above 10,000 IU/L), reflecting active muscle membrane damage and necrosis. CK elevation may be detectable before clinical symptoms appear and is used for neonatal and newborn screening. In myotonic dystrophy, CK is mildly elevated or normal. Genetic testing is now the definitive and first-line diagnostic test for most MDs: multiplex ligation-dependent probe amplification (MLPA) detects deletions and duplications in the DMD gene (present in 70-80% of DMD/BMD); gene sequencing detects point mutations and small indels. Accurate molecular characterisation of the specific mutation and exon(s) involved determines eligibility for exon-skipping therapies (e.g., exon 51 skipping is applicable to approximately 13% of DMD patients). For myotonic dystrophy, triplet repeat sizing by Southern blot or PCR quantifies CTG repeat length — predicting severity and anticipation. Muscle biopsy with haematoxylin and eosin staining, immunohistochemistry for dystrophin (absent in DMD, reduced and abnormal in BMD), and Western blotting can confirm or characterise diagnosis when genetic testing is inconclusive. Electromyography (EMG) demonstrates myopathic features (brief, small-amplitude, polyphasic motor unit potentials) and myotonic discharges in myotonic dystrophy. Cardiac assessment: 12-lead ECG (arrhythmias in DM1/EDMD) and echocardiogram (dilated cardiomyopathy in DMD/BMD) at diagnosis and annually. Pulmonary function tests (FVC, FEV1) and overnight oximetry monitor respiratory decline. Brain MRI in symptomatic DMD patients evaluating cognitive or behavioural difficulties.

Management of muscular dystrophy is multidisciplinary, combining disease-modifying pharmacotherapy (where available), organ system surveillance, and supportive care. Corticosteroids for DMD: deflazacort (0.9 mg/kg/day) or prednisone (0.75 mg/kg/day) are the standard of care — delaying loss of ambulation by 2-3 years, slowing respiratory decline, and reducing scoliosis severity and cardiomyopathy risk; the CINRG DNHS trial confirmed long-term survival benefit of corticosteroid use. Side effects (weight gain, vertebral fractures, growth suppression, cushingoid features, cataracts) require active monitoring and management. Givinostat (histone deacetylase inhibitor) has received EU approval for ambulatory DMD patients regardless of corticosteroid use. Exon-skipping therapies for DMD (mutation-specific, aiming to restore the reading frame and produce truncated functional dystrophin): eteplirsen (exon 51 — Sarepta, FDA-approved); golodirsen and viltolarsen (exon 53); casimersen (exon 45) — these apply to approximately 30% of DMD patients cumulatively. Delandistrogene moxeparvovec (SRP-9001 — FDA accelerated approval 2023): AAV-mediated micro-dystrophin gene therapy delivering a shortened but functional dystrophin construct — applicable to ambulatory DMD patients aged 4-5. Cardiac management: all DMD patients require ACE inhibitors (perindopril or lisinopril) from age 10 (or at first evidence of cardiomyopathy) and beta-blockers (carvedilol) for dilated cardiomyopathy — shown to slow progression. Respiratory management: non-invasive positive pressure ventilation (BiPAP/NIV) when FVC drops below 50% or symptoms of nocturnal hypoventilation develop; tracheostomy in end-stage respiratory failure for those choosing invasive ventilation. Scoliosis: posterior spinal instrumented fusion when Cobb angle exceeds 20-30 degrees and FVC is adequate for anaesthesia. Myotonic dystrophy: mexiletine for symptomatic myotonia; pacemaker/ICD implantation for significant cardiac conduction disease. Physiotherapy, orthotics (ankle-foot orthoses), assistive technology, and rehabilitation are central to maintaining function at all stages.

Cardiorespiratory failure is the leading cause of death in DMD — dilated cardiomyopathy develops in virtually all DMD patients by age 18 and causes heart failure and life-threatening arrhythmias; respiratory muscle weakness leads to nocturnal hypoventilation, chronic hypercapnic respiratory failure, and death from respiratory failure in the second to third decade without ventilatory support. Corticosteroid-related complications are near-universal with long-term use: vertebral compression fractures (osteoporotic — bisphosphonate prophylaxis is recommended), excessive weight gain causing obesity (exacerbating mobility loss), cataracts, hypertension, glucose intolerance, and growth suppression. Scoliosis develops in 60-90% of non-ambulatory DMD patients — severely impairing pulmonary function, causing pain, and complicating respiratory management. Contractures (shortening of muscles and tendons) at the ankles, hips, and knees cause pain, loss of functional positioning, and accelerate loss of ambulation — regular physiotherapy and nighttime splinting are preventive. Swallowing difficulties (dysphagia) in advanced DMD and oculopharyngeal MD cause aspiration, aspiration pneumonia, and malnutrition — modified diet and percutaneous gastrostomy may be required. Sudden cardiac death from arrhythmia is a major risk in myotonic dystrophy (DM1/DM2) and Emery-Dreifuss MD — cardiac monitoring and prophylactic pacemaker or ICD implantation are life-saving. Fractures from osteoporosis, falls, and immobility are common and may be the first presenting feature of advanced disease in ambulatory patients.

Primary prevention of muscular dystrophy focuses on genetic counselling, carrier testing, and reproductive planning for families with a known history. Female carriers of DMD gene mutations have a 50% risk of an affected son per pregnancy — molecular carrier testing identifies at-risk women who may not have been diagnosed. Prenatal diagnosis via chorionic villus sampling (CVS) at 10-13 weeks or amniocentesis at 15-20 weeks enables definitive genetic diagnosis of the foetus in families with a known pathogenic variant. Preimplantation genetic testing (PGT-M) during IVF allows selection of unaffected embryos — an option for carrier couples seeking a pregnancy unaffected by DMD or other hereditary MDs. Newborn screening for DMD using dried blood spot CK measurement followed by genetic confirmation is now implemented in several countries (Scotland, US state pilots), enabling pre-symptomatic diagnosis and initiation of corticosteroid therapy before irreversible muscle damage accumulates. Annual surveillance for all established DMD patients includes cardiac assessment (ECG, echocardiogram), pulmonary function tests (FVC, peak cough flow, overnight oximetry), orthopaedic review (scoliosis, contractures), bone health (DEXA scan, vitamin D, calcium), nutritional assessment, and neurodevelopmental support. Bone protection during corticosteroid therapy: calcium (1000mg/day) and vitamin D (800-1000 IU/day) supplementation, bisphosphonate therapy (zoledronic acid) for established vertebral fracture or low BMD.

Parents should seek paediatric assessment for: a boy aged 3-5 who has difficulty running, climbing stairs, or rising from the floor; walking on tiptoes; frequent falls; enlarged calf muscles (pseudohypertrophy); or unexplained delay in walking (beyond 18 months). Elevated serum CK in a symptomatic child should prompt urgent referral to a paediatric neurologist. Adults with suspected Becker MD or LGMD who develop progressive muscle weakness, high CK, or cardiac arrhythmias should be referred urgently to a neuromuscular specialist. Seek emergency care for: acute respiratory failure in a person with known muscular dystrophy (respiratory muscle weakness — emergency NIV required); new-onset significant cardiac symptoms (palpitations, syncope, breathlessness at rest — cardiomyopathy and arrhythmia are common causes of death in DMD and EDMD); or fractures from minor trauma (osteoporosis from steroids and immobility). All patients with DMD should be enrolled in a specialist neuromuscular centre for multidisciplinary care from diagnosis — including cardiac monitoring (annual ECG and echocardiogram), respiratory assessment (spirometry and overnight oximetry), bone health management, and orthopaedic review.