Muscular dystrophy and myotonic dystrophy

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

The term muscular dystrophy describes chronic genetically determined muscle fibre loss and replacement by fat and connective tissue. It does not specify inheritance or organ risk. Dystrophinopathies are X linked; facioscapulohumeral dystrophy is usually autosomal dominant; limb-girdle disorders may be dominant or recessive; and myotonic dystrophy is autosomal dominant with anticipation. A three-generation family history is useful, but de novo variants, variable expression and small families mean absence of family history does not exclude disease.

Myotonic dystrophy is multisystem rather than simply a myopathy. In type 1, a CTG repeat expansion in DMPK can enlarge between generations, particularly through maternal transmission, producing congenital disease. Adults may first present with cataract, infertility, diabetes, excessive sleepiness or atrioventricular conduction disease before muscle weakness is recognised. Type 2 has a different repeat expansion and more proximal pain or weakness. Routine serum genetic methods may not detect repeat expansions unless the correct assay is requested.

Care should be delivered by a neuromuscular multidisciplinary service. Respiratory muscle weakness may first appear during sleep, so symptoms and overnight testing matter before daytime saturation falls. Cardiomyopathy and conduction block can be clinically silent. Physiotherapy preserves range without eccentric overloading; contracture and scoliosis care supports ventilation and seating. Current disease-specific medicines and gene approaches have strict variant, age and commissioning criteria, so no general textbook regimen should be applied outside the specialist pathway.

Key points

Muscular dystrophies are genetically diverse disorders causing progressive muscle degeneration; age at onset, distribution, contractures, cardiac involvement and inheritance guide the initial differential.
Duchenne muscular dystrophy usually presents in early childhood with delayed motor milestones, calf pseudohypertrophy, Gowers manoeuvre and very high creatine kinase due to absent dystrophin.
Becker dystrophy results from partially functional dystrophin and is often milder or later, but cardiomyopathy can be disproportionate to skeletal weakness.
Facioscapulohumeral dystrophy produces facial weakness, scapular winging and humeral involvement, often asymmetrically, with hearing and retinal surveillance needed in selected patients.
Limb-girdle muscular dystrophies are genetically heterogeneous and may preferentially involve pelvic or shoulder girdles with variable cardiac and respiratory risk.
Myotonic dystrophy type 1 causes delayed muscle relaxation, distal and facial weakness, early cataract, conduction disease, sleepiness, respiratory failure, gastrointestinal dysmotility and endocrine features.
Percussion or grip myotonia is best demonstrated by asking the patient to release a sustained hand grip or tapping thenar muscle, while cold can accentuate delayed relaxation.
Creatine kinase may be strikingly raised in dystrophinopathy but only mildly abnormal in myotonic or facioscapulohumeral disease; a normal result does not exclude inherited muscle disease.
Genetic testing should confirm the diagnosis and guide family counselling before muscle biopsy whenever a recognised molecular pathway is available.
Management is anticipatory: corticosteroid and mutation-specific treatment for selected dystrophinopathy, cardiac and ventilatory surveillance, stretching, bone health, vaccination, rehabilitation and planned transition to adult services.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Dystrophinopathy

Pathogenic DMD variants reduce or abolish dystrophin, producing Duchenne or Becker phenotypes with X-linked skeletal and cardiac muscle disease.

Limb-girdle and facioscapulohumeral disease

Diverse dominant or recessive variants affect sarcolemmal, repair and structural proteins, creating patterned shoulder, pelvic, facial or scapular weakness.

Myotonic dystrophy

Repeat expansions cause toxic RNA effects in myotonic dystrophy, producing multisystem disease as well as distal or proximal weakness and delayed relaxation.

Other inherited muscle disease

Congenital, metabolic and mitochondrial variants can resemble a dystrophy and require phenotype-led genomic testing rather than assumption from weakness distribution alone.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Structural protein failure
Defective sarcolemmal or supporting proteins make muscle fibres vulnerable to contraction-related injury and calcium dysregulation over time.
2
Repeated degeneration and repair
Cycles of fibre necrosis, inflammation and incomplete regeneration progressively replace muscle with fat and fibrous tissue.
3
Loss of force and contracture
Declining functional fibres cause patterned weakness, while fibrosis and muscle imbalance shorten joints and deform the skeleton.
4
Toxic RNA mis-splicing
In myotonic dystrophy, expanded-repeat RNA sequesters regulatory proteins, disrupting splicing in muscle, heart, lens, endocrine and nervous systems.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Dystrophinopathy child

Delayed running, frequent falls, toe walking, calf enlargement and using hands to climb up the thighs when rising are classic early Duchenne features.

Scapulofacial pattern

Inability to whistle or close eyes firmly, a transverse smile and asymmetric scapular winging with preserved forearm strength suggests facioscapulohumeral dystrophy.

Grip myotonia

After forceful hand closure the fingers open slowly, while percussion of thenar or tongue can trigger a prolonged contraction without pain.

Myotonic systemic clues

Frontal balding, ptosis, early cataracts, daytime sleepiness, infertility, diabetes and gastrointestinal dysmotility accompany distal and facial weakness.

Cardiorespiratory warningRed flag

Syncope, palpitations, orthopnoea, recurrent chest infection, morning headache or daytime somnolence can signal conduction disease or nocturnal hypoventilation.

Limb-girdle pattern

Pelvic or shoulder weakness with preserved sensation and variable calf hypertrophy, contracture or cardiomyopathy suggests a genetically heterogeneous limb-girdle dystrophy.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Creatine kinase, liver enzymes and metabolic profileFirst step
Why
Detect muscle membrane injury and common mimics.
Interpretation and limitations
Dystrophinopathy often produces very high CK and muscle-derived transaminases; check GGT and clinical context before mislabelling isolated ALT or AST as liver disease.
02
Genomic testing
Why
Confirm the causal variant or repeat expansion and enable accurate family counselling.
Interpretation and limitations
Use the NHS Genomic Test Directory pathway, requesting deletion or duplication, sequence or repeat-expansion methods appropriate to the phenotype; a broad negative panel may need specialist reinterpretation.
03
ECG, ambulatory monitoring and echocardiography
Why
Detect silent conduction disease, arrhythmia and cardiomyopathy.
Interpretation and limitations
Myotonic dystrophy conduction intervals and dystrophinopathy ventricular function require scheduled surveillance; syncope or new abnormalities need expedited electrophysiology or cardiology review.
04
Forced vital capacity and respiratory pressures
Why
Measure respiratory-muscle reserve in sitting and supine positions.
Interpretation and limitations
A marked supine fall suggests diaphragmatic weakness; symptoms, cough flow and overnight carbon-dioxide assessment may reveal disease before daytime spirometry becomes severe.
05
Overnight oximetry or sleep study with carbon dioxide
Why
Detect nocturnal hypoventilation and coexisting obstructive sleep apnoea.
Interpretation and limitations
Oximetry alone may miss hypoventilation; transcutaneous carbon dioxide and respiratory specialist interpretation guide non-invasive ventilation.
06
Swallow and nutritional assessment
Why
Identify aspiration, prolonged meals, weight loss or obesity-related respiratory burden.
Interpretation and limitations
Clinical examination may need videofluoroscopy or endoscopy; recurrent pneumonia can be the presenting consequence of silent aspiration.
07
Endocrine, eye and bone assessment
Why
Detect cataract, diabetes, hypogonadism, osteoporosis and corticosteroid complications.
Interpretation and limitations
Select surveillance by genotype, age and treatment, ensuring bone protection and puberty or fertility support are not postponed behind motor care.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Inflammatory myopathy

Subacute proximal weakness, inflammatory skin or lung features and active muscle oedema favour immune myositis over a longstanding inherited pattern.

Metabolic or endocrine myopathy

Episodic exertional symptoms, endocrine signs or a biochemical trigger supports a metabolic cause that may be treatable.

Neuropathy or motor neurone disease

Sensory loss, reduced nerve responses, fasciculation or upper motor-neurone signs localise outside muscle despite apparent weakness and wasting.

Myasthenia gravis

Fluctuating ocular-bulbar weakness with normal muscle enzymes and fatigable transmission supports junctional disease rather than fibre degeneration.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Pattern recognitionMove from weakness distribution to genomic diagnosisFirst stepProgressive muscle weakness, myotonia or a suggestive family history is identified.

1Map facial, scapular, axial, proximal and distal weakness, contractures, calf size and myotonia while checking sensation, reflexes, cardiac and respiratory symptoms.
2Construct a three-generation pedigree and obtain CK, ECG and targeted systemic tests, referring to a neuromuscular and clinical genetics service.
3Use the phenotype-directed NHS genomic test, explaining uncertain variants and avoiding irreversible predictive testing in relatives without genetic counselling.

02Cardiorespiratory surveillanceFind silent organ disease earlyAn inherited dystrophy is confirmed or strongly suspected.

1EscalationEstablish baseline ECG, echocardiography and ambulatory rhythm assessment at the genotype-specific interval, escalating syncope or conduction change urgently.
2Measure sitting and supine vital capacity, cough effectiveness and sleep symptoms, arranging carbon-dioxide-inclusive overnight assessment when hypoventilation is possible.
3Introduce cardioprotective treatment, cough augmentation or non-invasive ventilation through specialist protocols before a crisis rather than waiting for daytime hypoxaemia.

03Function preservationSupport mobility without overwork injuryWeakness, contracture or fatigue begins to limit participation.

1Provide regular stretching, orthoses and low-to-moderate aerobic or submaximal resistance activity, avoiding high-load eccentric exercise that provokes prolonged damage.
2Review seating, powered mobility, transfers, home and school or workplace access early, presenting equipment as energy conservation rather than treatment failure.
3Monitor scoliosis, pain, bone density, nutrition and corticosteroid effects with orthopaedic, endocrine, dietetic and rehabilitation colleagues.

04Procedure planningMake anaesthesia and sedation saferA person with muscular or myotonic dystrophy needs surgery, endoscopy, dental sedation or childbirth planning.

1Alert an experienced anaesthetic team well in advance with the genotype, respiratory tests, cardiac findings, swallowing risk and complete medicine list.
2Avoid assumptions about malignant hyperthermia while addressing the genuine risks of succinylcholine, hyperkalaemia, myotonia, respiratory depressants and prolonged postoperative weakness.
3Plan warming, airway, cough support, non-invasive ventilation and monitored recovery or critical care, avoiding same-day discharge when multisystem risk is substantial.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Prolongs motor function and may support respiratory and cardiac outcomes in eligible Duchenne muscular dystrophy.

Prednisolone or deflazacort in Duchenne dystrophy

A paediatric neuromuscular specialist chooses the current daily or intermittent weight-based regimen, titrating for function, growth and adverse effects.

Monitor growth, weight, blood pressure, glucose, cataract, behaviour, infection, adrenal suppression, puberty and bone; never stop long-term corticosteroid abruptly.

Sodium-channel blockade can reduce grip and percussion myotonia, improving hand and jaw function.

Mexiletine

For disabling myotonia, specialists select a divided oral dose after baseline cardiac assessment and titrate according to the current BNF and local protocol.

Review structural heart disease, conduction intervals, arrhythmia, liver function, interactions and gastrointestinal adverse effects; it does not treat progressive weakness.

Treats or delays cardiomyopathy complications in dystrophinopathy and selected other muscular dystrophies.

Cardioprotective therapy

ACE inhibitor, angiotensin-receptor blocker, beta-blocker or mineralocorticoid-antagonist dosing follows cardiology assessment, ventricular function and current heart-failure guidance.

Monitor blood pressure, kidney function, potassium, conduction and pregnancy; beta-blockade may worsen fatigue and requires individual titration.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Cardiomyopathy and conduction disease

Dystrophin and myotonic disorders can cause heart failure, atrioventricular block and sudden arrhythmic death despite modest skeletal symptoms.

Respiratory failure

Diaphragm weakness, scoliosis and sleep hypoventilation reduce ventilatory reserve and cough, promoting infection and perioperative risk.

Dysphagia and anaesthetic risk

Bulbar weakness causes aspiration and malnutrition, while respiratory, cardiac and myotonic responses complicate sedation, surgery and recovery.

Endocrine, visual and mobility disability

Cataract, diabetes, fatigue, contracture and progressive weakness can affect education, work, fertility, independence and family planning.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Use genotype-specific scheduled ECG, ambulatory rhythm and ventricular imaging, acting on syncope or conduction change between routine visits.
Measure respiratory function, cough flow, sleep quality, morning headache and infection burden regularly, including carbon dioxide when hypoventilation is suspected.
Track swallowing, meal duration, weight and aspiration, involving speech therapy and dietetics before nutrition or chest infections deteriorate.
Review contractures, scoliosis, falls, pain, mobility equipment and participation with physiotherapy and occupational therapy at each disease transition.
During corticosteroid therapy monitor growth, puberty, adrenal safety, bone density, vitamin D, cataract, blood pressure, weight, glucose and vaccination.
Update genetic counselling for reproductive decisions and cascade testing, respecting autonomy and special consent issues for predictive testing in children.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Transaminases may be muscle

Marked ALT and AST with high CK and normal GGT can arise from muscle, preventing an unnecessary liver pathway while weakness remains unrecognised.

Heart can lead limbs

Dystrophinopathy or myotonic conduction disease may be clinically important before skeletal disability becomes severe, so surveillance cannot be symptom triggered alone.

Sleep reveals breathing

Diaphragmatic weakness first causes nocturnal hypercapnia, morning headache and somnolence while daytime oxygen saturation still appears normal.

Myotonia is delayed release

The complaint may be inability to let go rather than weakness; repeated action often warms the muscle and shortens relaxation in myotonic dystrophy.

Anaesthetic risk is specific

Myotonic dystrophy is not simply synonymous with malignant hyperthermia, but respiratory depression, aspiration, conduction problems and drug-triggered myotonia demand planning.

11Common pitfallsFrequent interpretation and management errors.

01
Excluding inherited dystrophy because no relative is known to be affected.
02
Attributing muscle-derived transaminases to primary liver disease without CK.
03
Waiting for daytime hypoxia before investigating nocturnal hypoventilation.
04
Ignoring cardiac surveillance when skeletal weakness seems mild.
05
Using a general gene panel that cannot detect repeat expansions appropriately.
06
Stopping chronic corticosteroid abruptly during illness or surgery.
07
Allowing unplanned sedation without neuromuscular anaesthetic assessment.