Paediatrics chapters
Duchenne muscular dystrophy
The commonest inherited muscle disease of boys: X-linked loss of dystrophin, calf pseudohypertrophy, Gowers sign, a very high CK, and supportive care with steroids.
- Duchenne muscular dystrophy is an X-linked recessive disease of boys caused by absent dystrophin; about one third of cases are new mutations.
- Boys present at about 2 to 5 years with clumsy, waddling gait, lordosis, difficulty with stairs, calf pseudohypertrophy and a positive Gowers sign; most stop walking by about 12 years.
- CK is hugely raised; genetic testing or muscle biopsy (no dystrophin) confirms; there is no cure, but steroids slow decline and heart and lung care prolong life.
On this page
Overview
Duchenne muscular dystrophy (DMD) is a genetic, progressive disease of muscle in which the muscle fibres break down and are slowly replaced by fibrous and fatty tissue. It is the most common muscular dystrophy and one of the commonest inherited disorders of childhood. It almost always affects boys, starts in the preschool years, takes away walking by early adolescence and later involves the heart and breathing muscles. The exam focus is the inheritance, the signs (Gowers sign, calf enlargement) and the role of CK.
Genetics and pathogenesis
- X-linked recessive inheritance; the gene lies at Xp21.
- The faulty gene cannot make dystrophin, a protein that anchors the inside of the muscle cell membrane to the surrounding matrix through a glycoprotein complex.
- Without dystrophin the membrane is fragile, fibres are damaged with each contraction, die, and are replaced by connective tissue and fat.
- About one third of cases arise from new mutations (Akbar gives about 30%), so a negative family history does not exclude it.
- Incidence is about 1 in 3,500 to 3,600 male births.
- Female carriers usually have no symptoms.
- Dystrophin is also present in the brain, which explains the mild learning problems.
Inheritance from a carrier mother
| Child | Chance |
|---|---|
| Son affected | 50% of sons |
| Son unaffected | 50% of sons |
| Daughter carrier | 50% of daughters |
| Daughter non-carrier | 50% of daughters |
Across all four children this means a 25% chance for each outcome.
Duchenne = Deleted Dystrophin, a Disease of boys.
Becker muscular dystrophy
Becker muscular dystrophy (BMD) is caused by a defect in the same gene at the same locus, but some working dystrophin is still made. It is milder, starts later and progresses more slowly.
Clinical features
Early course
- Newborn and young infant boys seldom show any problem.
- Early motor milestones are normal or mildly delayed; some have poor head control or late walking.
- From about 2 to 3 years, the boy becomes clumsy, falls often, cannot run properly and has trouble climbing stairs.
Signs on examination
- Waddling gait with exaggerated lumbar lordosis (hip girdle weakness).
- Proximal weakness, legs first; arm weakness is clear by about 6 years.
- Gowers sign: to get up from the floor the child turns prone, then walks his hands up his legs to push himself upright, because the hip and thigh muscles are weak.
- Calf pseudohypertrophy: firm, bulky calves; the bulk is fat and fibrous tissue, not strong muscle. After the calves, the tongue and forearm muscles are the next commonest sites of enlargement.
- No fasciculations of the tongue (unlike spinal muscular atrophy).
- Distal muscles are relatively spared, so the boy can still hold a pen and feed himself late into the illness.
- Muscle breakdown is painless: there are no myalgias or cramps.
- Sensation is normal.
Gowers sign shows proximal pelvic girdle weakness. It is classic for DMD but is seen in any disease with weak hip extensors.
Later course
| System | What happens |
|---|---|
| Mobility | Most lose walking between 8 and 12 years and are wheelchair users by about 12 |
| Joints | Contractures at ankles (heel cords), knees, hips and elbows |
| Spine | Scoliosis is common, worse once in a wheelchair |
| Lungs | Weak cough, repeated chest infections, falling reserve, then respiratory failure |
| Heart | Cardiomyopathy in roughly half or more (Akbar: 50 to 80%), with persisting tachycardia and heart failure |
| Brain | Mild intellectual impairment is common; a minority (Akbar: 20 to 30%) have an IQ below 70; some have behavioural problems |
Investigations
| Test | Finding and meaning |
|---|---|
| Serum creatine kinase (CK) | Very high (Akbar quotes many thousands of IU/L against a normal under 160). Raised from birth, before weakness appears. A normal CK practically excludes DMD |
| Other muscle enzymes | Aldolase and AST are also raised (less specific) |
| Genetic testing (PCR / DNA) | Detects the dystrophin gene mutation; the main confirmatory test today; allows carrier testing and prenatal diagnosis |
| Muscle biopsy | Fibre degeneration and regeneration, increased connective tissue; immunostaining shows absent dystrophin |
| EMG | Myopathic pattern, no denervation (not specific) |
| Nerve conduction | Normal (motor and sensory) |
| Heart | ECG, echocardiography and chest X-ray to look for cardiomyopathy |
A raised AST or ALT in a young boy with no liver signs may come from muscle. Check the CK before ordering liver work-up.
CK is the screening test for brothers and other at-risk relatives of an affected boy; DNA testing confirms and identifies carriers.
Differential diagnosis
| Condition | Key difference |
|---|---|
| Becker dystrophy | Same gene, partly working dystrophin; milder, more protracted course |
| Limb-girdle dystrophy | Usually autosomal recessive; affects both sexes; hip and shoulder girdles |
| Spinal muscular atrophy | Tongue fasciculations, absent reflexes, CK normal or only mildly raised, neurogenic EMG |
| Myotonic dystrophy | Autosomal dominant; myotonia (slow release of grip), distal wasting, facial weakness |
| Cerebral palsy | Non-progressive, upper motor neuron signs, CK normal |
Myotonic dystrophy in brief
- Autosomal dominant; an expanding CTG triplet repeat on chromosome 19; shows anticipation (earlier and worse in each generation).
- Facial weakness, ptosis, hollow temples, an inverted V-shaped upper lip, distal wasting, and myotonia (the hand cannot let go after a handshake).
- Also cataracts, heart conduction problems, endocrine disease (diabetes, hypothyroidism) and gut smooth muscle problems.
- A congenital form occurs in babies of affected mothers: a floppy, weak newborn with feeding and breathing problems.
Management
There is no curative treatment. Care aims to keep the boy walking as long as possible, prevent complications and improve quality of life, ideally through a multidisciplinary team.
Drugs
- Corticosteroids slow the loss of strength and delay disability. Akbar describes an intermittent plan: prednisolone 0.75 mg/kg/day, given on days 1 to 10 of every month, a schedule chosen to reduce long-term steroid side effects.
- Heart failure from cardiomyopathy: Akbar starts with digoxin; other heart failure drugs are used as needed.
Supportive care
- Physiotherapy, stretching, bracing and good seating to delay contractures; suitable wheelchair when walking is lost.
- Orthopaedic care for contractures and scoliosis.
- Treat chest infections early; avoid contact with children who have respiratory infections; give influenza vaccine.
- Breathing support when respiratory muscles fail.
- Diet: enough calcium (steroids and immobility weaken bone) and a balanced intake to avoid obesity.
- Genetic counselling, carrier testing of female relatives and prenatal diagnosis.
Boys with DMD are at risk of a malignant hyperthermia-like reaction with some anaesthetic agents; the anaesthetist must know the diagnosis.
Prognosis and causes of death
- Life expectancy has improved with steroids and better respiratory and cardiac care. Akbar gives death at about 17 to 20 years; Nelson notes many now live into their 20s or early 30s.
- Main causes of death: respiratory failure, pneumonia, aspiration and airway obstruction, and intractable heart failure.
Expect: X-linked recessive inheritance with dystrophin absence at Xp21; one third new mutations; boy aged 3 to 5 with waddling gait, lordosis, frequent falls, stair difficulty; Gowers sign; calf pseudohypertrophy; no tongue fasciculations; very high CK as the screening test (normal CK excludes); confirmation by DNA testing or biopsy showing no dystrophin; myopathic EMG with normal nerve conduction; loss of walking by about 12; cardiomyopathy and respiratory failure as causes of death; steroids to slow decline; Becker as the milder form; and myotonic dystrophy as the autosomal dominant contrast.
Quick revision
- X-linked recessive, Xp21, no dystrophin; one third new mutations; boys.
- Onset 2 to 5 years: clumsy, falls, waddling gait, lordosis, stairs difficult.
- Gowers sign; calf pseudohypertrophy; distal function kept; no fasciculations.
- CK hugely raised from birth; normal CK excludes DMD.
- DNA testing or biopsy (no dystrophin) confirms; EMG myopathic; NCV normal.
- Wheelchair by about 12; contractures and scoliosis follow.
- Cardiomyopathy and respiratory failure kill.
- No cure: steroids, physiotherapy, chest and heart care, counselling.
- Becker: same gene, milder; myotonic dystrophy: autosomal dominant, CTG repeat.
Written by The House Job from standard references (Basis of Paediatrics by Pervez Akbar; Nelson Essentials of Paediatrics).
FAQ
Why are the calves big if the muscles are weak?
The enlargement is pseudohypertrophy: damaged muscle is replaced by fat and fibrous tissue, so the calves look bulky but are weak.
Which test should be done first in a boy suspected of DMD?
Serum creatine kinase. It is very high even before symptoms, and a normal value almost rules the disease out; genetic testing then confirms it.
Can girls have Duchenne muscular dystrophy?
Girls are usually healthy carriers because the disease is X-linked recessive; affected boys inherit the faulty X from a carrier mother or have a new mutation.
Do steroids cure DMD?
No. They slow the loss of strength and delay disability, but the disease still progresses, so physiotherapy, heart and lung care remain essential.