Muscular Dystrophy — Causes, Symptoms, Diagnosis & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Muscular dystrophies are a heterogeneous group of inherited genetic diseases characterised by progressive skeletal muscle weakness and degeneration due to defects in genes encoding structural muscle proteins. Over 30 types have been identified, varying in inheritance pattern, age of onset, muscles affected, rate of progression, and systemic involvement. The most common and severe forms include: Duchenne muscular dystrophy (DMD — most common childhood form; X-linked recessive; caused by dystrophin gene mutations, onset ages 2-5, typically wheelchair-dependent by teenage years), Becker muscular dystrophy (BMD — similar to DMD but milder; partially functioning dystrophin produced), myotonic dystrophy (most common adult form; autosomal dominant; CTG trinucleotide repeat expansion in DMPK gene — causes myotonia and multisystem involvement), limb-girdle muscular dystrophies (LGMD — a genetically diverse group), facioscapulohumeral MD (FSHD), and congenital muscular dystrophies. No cure exists for most forms, but disease-modifying therapies are transforming outcomes in DMD.

Muscular dystrophies are caused by mutations in genes encoding structural proteins of the muscle fibre and its membrane complex. DMD and BMD: mutations in the dystrophin gene (DMD gene on the X chromosome — Xp21; encoding the largest human gene) — deletions (68%), duplications (11%), or point mutations. Absence of dystrophin (DMD) leads to membrane fragility, calcium influx, muscle fibre necrosis, and replacement by fibrotic and fatty tissue. Myotonic dystrophy type 1: CTG repeat expansion in the 3' UTR of DMPK gene; type 2: CCTG repeat in CNBP gene — both cause aberrant splicing of multiple mRNAs. LGMDs: mutations in calpain-3, dysferlin, gamma-sarcoglycan, anoctamin-5, and dozens of other proteins. FSHD: contraction of the D4Z4 macrosatellite repeat array at chromosome 4q35 leading to aberrant DUX4 expression in muscle. Many cases have no family history — de novo mutations in DMD account for approximately 30% of cases.

Duchenne MD: typically diagnosed between ages 2-5, presenting with delayed motor milestones, waddling gait, difficulty climbing stairs and rising from the floor (Gowers' sign — using hands to walk up the body from a squat position), frequent falls, calf pseudohypertrophy (enlarged but weak calves from replacement of muscle with fat and connective tissue), and learning difficulties (cognitive involvement due to dystrophin in neurons). Wheelchair dependence typically by age 10-13. Cardiac involvement (dilated cardiomyopathy) and respiratory failure (from diaphragm and intercostal muscle weakness) develop in teens and early adulthood. Without treatment, median survival was 19 years; with corticosteroids and modern respiratory/cardiac management, many DMD patients now survive into the 30s-40s. Myotonic dystrophy: muscle weakness and myotonia (delayed relaxation after grip — difficulty releasing a handshake), ptosis, facial weakness, dysarthria, cataracts, cardiac conduction defects (potentially fatal arrhythmias), glucose intolerance, sleep apnoea, daytime somnolence, cognitive and personality changes, and male hypogonadism. FSHD: slowly progressive weakness of facial (inability to whistle, smile fully), shoulder girdle (scapular winging), upper arm, and later hip girdle muscles — highly asymmetric.

Serum creatine kinase (CK): markedly elevated in DMD (20-100 times normal) and Becker MD from the earliest age (even before symptoms); also elevated in other myopathies. Genetic testing: panel-based gene testing or next-generation sequencing identifies mutations in the relevant MD gene — DMD gene deletion/duplication analysis (MLPA) is first-line; point mutations detected by sequencing. Muscle biopsy: histology shows muscle fibre degeneration, necrosis, inflammatory infiltrate, and fibrofatty replacement; immunohistochemistry demonstrates absent (DMD) or reduced (BMD) dystrophin protein on the muscle fibre membrane; Western blotting quantifies dystrophin protein. Cardiac assessment: echocardiography (dilated cardiomyopathy in DMD) and ECG (myotonic dystrophy — PR prolongation, complete heart block risk) at diagnosis and regular intervals. Respiratory function tests (FVC, peak cough flow) — guide ventilation timing. MRI skeletal muscle: characterises the pattern of muscle involvement — useful in LGMD diagnosis and monitoring. EMG (electromyography): distinguishes myopathic from neuropathic pattern. Genetic counselling and carrier testing for female relatives of X-linked MDs.

Duchenne MD — disease-modifying therapy: corticosteroids (deflazacort or prednisolone — first-line standard of care from age 4-5) slow disease progression by 2-3 years, preserve ambulation, and protect cardiac and respiratory function — mechanism incompletely understood but involves anti-inflammatory and possibly muscle fibre preservation effects. Exon skipping (antisense oligonucleotides — ASOs): eteplirsen (exon 51 skip — FDA-approved, UK under evaluation), viltolarsen, casimersen — restore the dystrophin reading frame in specific deletion mutations, enabling production of a shorter but functional dystrophin protein (applicable to approximately 15-30% of patients depending on exon). Ataluren (Translarna — NICE-approved for UK): for nonsense (stop-codon) mutations (approximately 13% of DMD) — allows ribosomal read-through. Delandistrogene moxeparvovec (Elevidys): mini-dystrophin gene therapy (AAV-delivered) — FDA-approved 2023 for DMD ages 4-5; under evaluation in UK. Cardiac: ACE inhibitors/ARBs (perindopril, losartan) started from age 10 for cardioprotection; beta-blockers. Respiratory: non-invasive ventilation (NIV — BiPAP) initiated when FVC falls below 50% predicted; cough-assist devices. Physio, orthotics, and scoliosis surgery. Myotonic dystrophy: mexiletine for myotonia; pacemaker for cardiac conduction defects; CPAP for sleep apnoea; no disease-modifying therapy currently approved (antisense oligonucleotide DMPK-targeting therapy in trials).

Respiratory failure is the leading cause of death in Duchenne MD — progressive weakness of the diaphragm, intercostal muscles, and accessory muscles of respiration causes nocturnal hypoventilation, then daytime respiratory failure, typically in the late teens to early 20s in untreated patients. Non-invasive ventilation (BiPAP) delays progression but tracheostomy is eventually required in some patients. Dilated cardiomyopathy develops in virtually all DMD patients by the late teens — reduced ejection fraction, left ventricular dilatation, and arrhythmias cause significant morbidity; ACE inhibitors and beta-blockers are cardioprotective but do not prevent eventual cardiac dysfunction. Myotonic dystrophy type 1 has high risk of fatal cardiac arrhythmias (complete heart block, ventricular tachycardia) — sudden cardiac death accounts for approximately 30% of DM1 mortality; prophylactic pacemaker implantation is indicated when PR interval exceeds 240 ms. Scoliosis develops in the majority of non-ambulatory DMD patients (70–90%) — progressive spinal curvature impairs respiratory mechanics and quality of life; posterior spinal fusion is performed when Cobb angle exceeds 20–25 degrees. Progressive joint contractures (particularly of ankles, hips, and knees) limit mobility and positioning — physiotherapy and orthoses slow progression. Aspiration pneumonia from pharyngeal weakness and impaired cough reflex is a major cause of hospitalisation and mortality. Cognitive and behavioural impairment from cerebellar dystrophin deficiency causes learning difficulties in approximately 30% of DMD patients. Osteoporosis from reduced mobility, corticosteroid use, and underlying metabolic abnormalities increases fracture risk.

Genetic counselling is essential for all families affected by muscular dystrophy. Carrier testing: females related to an X-linked MD patient (DMD, Becker) can be tested for carrier status — carriers have a 50% chance of passing the mutation to each son (who would be affected) and each daughter (who would be a carrier). Preimplantation genetic testing (PGT-M) during IVF enables selection of unaffected embryos for families who have chosen this option. Prenatal diagnosis (chorionic villus sampling at 11-14 weeks or amniocentesis at 15-17 weeks) is available for known familial mutations. Newborn screening for DMD is under implementation in several countries — early identification enables treatment initiation before irreversible muscle damage accumulates. Neonatal screening via dried blood spot CK measurement can detect DMD from birth.

Consult a paediatric neurologist promptly for: a child with delayed motor milestones (not walking by 18 months), frequent falls, difficulty climbing stairs, getting up from the floor (Gowers' sign), enlarged calves, or unexplained elevated CK on blood testing. Early diagnosis is critical — corticosteroid and disease-modifying therapy initiation should ideally begin before age 5 to maximise benefit. Contact your neuromuscular team urgently for: respiratory infection in DMD (can cause acute respiratory failure requiring hospital admission and ventilatory support), unexplained cardiac symptoms (palpitations, breathlessness, oedema), or rapid worsening of motor function. Adults with myotonic dystrophy should have annual cardiac monitoring (pacemaker needed if PR interval above 240 ms or second/third-degree AV block).