Muscular dystrophies

• Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by loss of the muscle protein dystrophin; it weakens the muscles of the hips and shoulders first, and most affected boys need a wheelchair by about 10 to 12 years of age.
• Becker muscular dystrophy (BMD) is a milder allelic condition: dystrophin is reduced or altered rather than absent, so people are usually diagnosed later and many retain walking into adulthood.
• Myotonic dystrophy type 1 (DM1) is a common adult-onset muscular dystrophy caused by an expanded CTG repeat in the DMPK gene; it gives myotonia, weakness, cataracts, frontal balding, heart conduction disease, and endocrine problems.
• DMD is confirmed by genetic testing (deletion/duplication testing first, then sequencing), and creatine kinase is markedly raised; in DM1 the creatine kinase is normal or only slightly raised.
• Care is multidisciplinary: glucocorticoids, stretching, respiratory and cardiac surveillance, bone health, nutrition, and, for DMD, mutation-specific drugs such as exon-skipping therapy; gene therapy is in active development.

By the end of this page you should be able to:

1. Explain why both DMD and BMD are dystrophinopathies, and how the type of mutation changes the severity.
2. Recognise DMD in a toddler (Gowers sign, calf pseudohypertrophy, proximal weakness, raised creatine kinase) and set out the diagnostic pathway.
3. Contrast DM1 with DMD in terms of inheritance, age of onset, pattern of weakness, and systemic features.
4. Describe the CTG repeat sizes that separate normal, variable and fully-variable DMPK alleles, and what anticipation means for counselling.
5. Plan multidisciplinary care for DMD across childhood, including glucocorticoid dosing, adrenal safety, respiratory and cardiac thresholds, and bone health.
6. Summarise the status of exon-skipping therapy, readthrough therapy, and gene replacement therapy for DMD and the targeted approaches being tested for DM1.

A muscular dystrophy is a group of inherited disorders in which muscle fibres break down and are replaced by fibrous and fatty tissue, leading to progressive weakness. This page covers three of the most important:

• Duchenne muscular dystrophy and Becker muscular dystrophy are caused by mutations in the same gene, DMD, which codes for the protein dystrophin. They form a continuous spectrum, split by whether functional dystrophin is essentially absent (Duchenne) or partly present (Becker).
• Myotonic dystrophy type 1 is caused by an expanded CTG trinucleotide repeat in the DMPK gene. It is the commonest muscular dystrophy with onset in adulthood and affects muscle, heart, eyes, brain, smooth muscle and endocrine organs.

Dystrophin is a large cytoskeletal protein that links the internal actin skeleton of a muscle fibre to the membrane and then to the surrounding matrix, so the membrane does not tear during contraction.^[3] In its absence the membrane becomes leaky, calcium enters, inflammation and fibrosis follow, and muscle is lost.^[3]

DMD occurs in about 15.9 per 100,000 live male births in the United States and 19.5 per 100,000 in the United Kingdom.^[1] Incidence estimates cluster around 1 in 5,000 boys worldwide.^[3][4] About one third of mutations arise de novo, so an affected boy may be born into a family with no history.^[3]

DM1 is the commonest muscular dystrophy that begins in adulthood. Clinical estimates place prevalence at about 1 in 6,000 to 1 in 10,000,^[7] whereas newer population-based genetic data suggest that up to about 1 in 2,100 people may carry an expansion, many with mild or unrecognised disease.^[7] Worldwide prevalence estimates are 1 in 5,000 to 1 in 20,000,^[5] and in parts of Quebec a founder effect raises it to about 1 in 550.^[5] Women and men are affected equally because DM1 is autosomal dominant.

Both conditions are X-linked recessive. A boy receives his single X chromosome from his mother; the father's Y chromosome carries no dystrophin gene. Each son of a carrier mother has a 1 in 2 chance of being affected, and each daughter a 1 in 2 chance of being a carrier.^[1] Approximately 60% of dystrophin mutations are deletions and 11% are duplications, with the rest being small mutations and splice changes.^[3] Mutations cluster in two hotspots, exons 3 to 9 and exons 45 to 55.^[3]

The difference between Duchenne and Becker is usually explained by the reading frame rule. Deletions or duplications that disrupt the reading frame abolish dystrophin production (Duchenne). Mutations that leave the reading frame intact produce a shorter but partly functional dystrophin protein (Becker), which is why Becker is milder.

Female carriers can be affected. Skeletal muscle involvement is uncommon but cardiomyopathy develops in a substantial minority; one study found that 47% of carriers had at least one abnormality on cardiac MRI.^[2] All carriers need a baseline cardiac assessment in early adulthood and then surveillance every 3 to 5 years.^[2]

DM1 is autosomal dominant, with nearly complete penetrance but variable expressivity.^[5] Some people are never diagnosed because their symptoms are mild. The mutation is an unstable expansion of a CTG repeat in the 3 untranslated region of DMPK on chromosome 19. Normal alleles have about 5 to 34 repeats. Alleles of 35 to 49 repeats (variable alleles) cause no symptoms in the carrier but are unstable and can grow in the next generation. Alleles of 50 or more repeats (fully-variable alleles) cause disease.^[5][6]

The expansion grows when transmitted, so later generations tend to be affected earlier and more severely. This is called anticipation. Congenital DM1, the severe neonatal form, is usually transmitted by the mother and involves very large expansions of 1,000 to 6,000 repeats.^[5][6] By contrast, a small proportion of inherited expansions are contractions (reverse alleles), which is one reason penetrance is not absolute.^[5]

Without dystrophin the link between cytoskeleton and membrane fails, so the sarcolemma tears during contraction and reseals badly.^[3] Calcium leaks in, inflammation is activated, muscle fibres necrose, and as regenerative capacity is exhausted fibrous and fatty tissue takes their place. Damage is greatest in muscle groups that work hardest, which explains the early pattern: limb girdle weakness first, then the respiratory and cardiac muscles.

This mechanism explains the bedside findings:

• Gowers sign arises because the hip extensors and quadriceps are weak; the child uses the hands to push up the thighs and "walks" the hands up the legs.
• Calf pseudohypertrophy is not true muscle growth: the gastrocnemius enlarges because dying muscle fibres are replaced by fat and fibrous tissue.
• Raised creatine kinase leaks from damaged fibres; in active disease serum creatine kinase is typically in the tens of thousands of units per litre.

Progression is predictable if not treated: wheelchair dependence usually occurs at about 12 years, assisted ventilation is needed around 20, and death from cardiac or respiratory failure usually happens between 20 and 30 years.^[3][4] Corticosteroids and modern multidisciplinary care have improved survival, and people with optimal care now often live into their thirties and forties.^[3]

Cardiac muscle is affected too, but more slowly. Membrane instability produces myocyte death, fibrosis and fatty replacement, leading to dilated cardiomyopathy, arrhythmia and heart failure.^[3] Respiratory muscle weakness reduces cough, retains secretions, and causes atelectasis, pneumonia and nocturnal hypoventilation; lower respiratory tract infections in a DMD patient can precipitate acute respiratory failure.^[3][2]

Becker differs because some dystrophin persists. Mutations cause loss of some exons but do not abolish dystrophin expression.^[3] The protein is shorter or reduced in quantity, yet still links cytoskeleton to membrane well enough to preserve function for years. Weakness still progresses, but far more slowly; patients and families may not seek help until adolescence or adulthood.

In DM1 the CTG expansion is transcribed into CUG repeat RNA, which is retained in the nucleus and sequesters RNA-binding proteins such as muscleblind-like protein 1. The result is a spliceopathy: mis-splicing of chloride channels produces myotonia, of the insulin receptor produces insulin resistance, and of numerous other transcripts produces the multi-organ picture.^[5] Repeat expansions are somatically unstable, larger in some tissues than in blood, which partly explains why clinical severity does not track blood repeat length in individual patients.^[5]

Boys look normal at birth. Weakness begins in the proximal muscles of the lower limbs at around 2 to 3 years.^[3][4] Parents notice delayed walking, toe walking, frequent falls and difficulty climbing stairs. The characteristic picture is a waddling (Trendelenburg) gait, calf pseudohypertrophy, lumbar lordosis and a positive Gowers sign.^[1][3] The creatine kinase is dramatically raised and the aminotransferases and lactate dehydrogenase may also be high, which sometimes sends the family down a wrong track of liver disease before the muscle disease is recognised.^[1]

Cognitive and behavioural difficulties are part of DMD rather than a coincidence: mean intelligence is about one standard deviation below the normal mean, intellectual disability is reported in roughly one third of patients, and attention deficit and autistic features are more common than in the general population.^[3][1]

Becker presents exactly like a milder Duchenne: the same proximal weakness and calf pseudohypertrophy, but onset later (sometimes late childhood or adult life), progression slower and creatine kinase usually lower. Many men with Becker remain ambulatory through adult life and some have near-normal life expectancy when the heart and lungs are spared.^[4] Becker is diagnosed with the same genetic tests, because the distinction is one of reading frame and of severity, not of a different gene.

DM1 looks different from dystrophinopathy in several ways.

Facial and neck features. Bilateral ptosis, temporalis wasting (a long thin face), and in men frontal balding are characteristic; the facial expression is flat or tired.^[6] The eyes may not close fully.

Muscle. The signature symptom is myotonia (delayed relaxation after contraction): difficulty releasing grip, opening the eyes after closure, or locking the jaw. It is often worse when cold and improves with repeated contraction (a warm-up phenomenon).^[6] Weakness is mainly distal (hands, ankles, neck flexors) and dysarthria and dysphagia emerge. Serum creatine kinase is normal or only slightly raised, which separates DM1 from dystrophinopathy.^[6]

Eyes. Cataracts are a hallmark, often appearing before 55 years, with a "Christmas tree" punctate iridescent appearance.^[6]

Heart. Cardiac conduction disease and atrial or ventricular arrhythmia are common; they may be silent in three quarters of those with ECG abnormalities.^[6] Cardiomyopathy and heart failure occur. Annual cardiac assessment is needed and a cardiologist experienced with DM1 should follow up.^[6]

Lungs. About one third of adults have reduced pulmonary function, but chronic hypercapnic respiratory failure develops as the disease progresses, and respiratory complications are the commonest cause of death.^[6]

Other. Diabetes mellitus and thyroid dysfunction, hyperlipidaemia, reproductive and fertility problems, fatigue (reported by up to 90%), excessive daytime sleepiness, cognitive and behavioural problems, gastrointestinal symptoms, and an increased risk of some malignancies all occur.^[6]

Congenital and childhood DM1. Severe neonatal DM1 produces hypotonia, feeding problems, and mechanical respiratory failure; neonatal mortality is about 16%, usually from respiratory failure.^[6] Talipes equinovarus occurs in about one third of congenital cases.^[6] Children may present with delayed milestones and cognitive or behavioural problems, with weakness and myotonia appearing later.

Creatine kinase is the screening test: it is raised, usually dramatically, in a boy with unexplained weakness, and should be checked before chasing liver disease.^[1] The diagnostic algorithm is almost always genetic because dystrophin mutations can be found in almost all cases.^[1]

Approximately 70% of people with DMD have a single-exon or multi-exon deletion or duplication in the dystrophin gene, so deletion and duplication testing, best done by multiplex ligation-dependent probe amplification (MLPA) or comparative genomic hybridisation array, is the usual first confirmatory test.^[1] If that is negative, genetic sequencing (next-generation sequencing) is done to detect point mutations, small insertions and deletions, which account for roughly 25 to 30% of cases.^[1] Only if genetic testing does not confirm the diagnosis is a muscle biopsy needed, to look for dystrophin protein by immunohistochemistry or western blot.^[1]

Carrier testing is recommended for female relatives of a genetically confirmed patient, with genetic counselling; reproductive options include preimplantation genetic diagnosis and prenatal testing by chorionic villus or amniotic fluid sampling.^[1]

DM1 is diagnosed by molecular testing for the DMPK CTG repeat expansion, using polymerase chain reaction and Southern blot methods which together detect all alleles.^[5] Targeted assessment of DMPK is preferred because the expansion can be missed or misinterpreted on whole-exome or genome sequencing.^[6] If the repeat size is in the variable range (35 to 49 repeats), Southern blot may be needed to exclude mosaicism.^[5] Genetic counselling is offered to the patient and relatives, including discussion of preimplantation and prenatal genetic diagnosis.^[6]

For DMD the diagnosis rests on a pathogenic dystrophin mutation or (rarely still) on absence of dystrophin protein on biopsy.^[1] Severity correlates with the mutation: loss of ambulation around 10 to 12 years is typical on supportive care alone, but is delayed by glucocorticoids.^[3][1]

For DM1 there are no severity scores in routine use, but age at onset divides the disease into congenital (onset under 1 month), childhood (1 month to 18 years), adult onset (18 to 40 years) and late onset (over 40 years), with severity generally tracking repeat size without being predictable in an individual.^[6][5]

The CTG repeat sizes and their clinical meaning are:

Limitations: blood repeat length underestimates tissue repeat length, repeat size alone cannot predict severity in one person, and interruptions within the repeat can slow expansion.^[5][6]

A neuromuscular specialist should lead a multidisciplinary team including physiotherapy, occupational therapy, cardiology, respiratory medicine, endocrinology, gastroenterology, orthopaedics, rehabilitation and dietetics, with psychosocial support. Assessment and anticipatory care, rather than waiting for complications, are the defining habit of modern DMD care.^[1][2]

Physiotherapy and glucocorticoid therapy are the standard of care and should continue after ambulation is lost.^[1] Benefits are later loss of walking, better upper limb and respiratory function, and less scoliosis surgery.^[1] A phase 3 double-blind trial compared deflazacort 0.9 mg/kg per day, deflazacort 1.2 mg/kg per day, prednisone 0.75 mg/kg per day and placebo; all corticosteroid groups improved muscle strength versus placebo, and deflazacort caused less weight gain than prednisone.^[1] Natural history data show prolongation of walking from a mean of 10.0 years with under one year of corticosteroid use to 11.2 years with daily prednisone and 13.9 years with daily deflazacort.^[1] Weekend-only prednisone has matched daily dosing in some studies, and starting before significant decline seems beneficial.^[1] No regimen has been shown to be clearly best, so the choice should be made by the neuromuscular team and the family.^{[1] [4]}

Glucocorticoids carry predictable problems: growth suppression, pubertal delay, bone fragility, weight gain, changed behaviour and adrenal suppression.

Adrenal safety. All patients on glucocorticoids must receive education about adrenal crisis and a prescription for intramuscular hydrocortisone to use at home: 50 mg for children under 2 years, 100 mg for children and adults 2 years or older.^[1] Stress dosing with hydrocortisone 50 to 100 mg per square metre per day may be needed during severe illness, major trauma or surgery for individuals taking more than 12 mg per square metre per day of prednisone or deflazacort.^[1] Never stop glucocorticoids abruptly; taper over weeks to months to allow recovery of the hypothalamic-pituitary-adrenal axis.^[1]

Growth and puberty. Check height every 6 months; refer to an endocrinologist if annualised height velocity is under 4 cm per year or if height falls under the third centile.^[1] Growth hormone is not routinely recommended in DMD.^[1] Puberty that has not started by age 14 needs referral; testosterone can be considered after age 12 and is recommended from 14, starting low and increasing over several years.^[1]

Bone health. 20 to 60% of boys with glucocorticoid-treated DMD have low-trauma limb fractures and up to 30% develop symptomatic vertebral fractures, which can end ambulation early.^[2] Baseline spine imaging is recommended rather than waiting for pain, and intravenous (not oral) bisphosphonate is first-line treatment for osteoporosis in DMD, via an osteoporosis specialist.^[2] Vertebral compression is an early warning; long-bone fractures carry a risk of fat embolism syndrome in DMD, with confusion, respiratory distress and tachycardia that need immediate care.^[2]

Nutrition. Body mass index should be kept between the 10th and 85th centiles on standard charts, although body composition in DMD is abnormal. Dietary calcium and serum 25-hydroxyvitamin D should be checked annually; if 25-hydroxyvitamin D is under 30 ng/mL or calcium intake is low, supplementation should be given.^[1] Constipation, reflux and dysphagia need proactive management, and dysphagia screening should start early.

Anticipatory pulmonary care has shifted to lower, earlier thresholds. Spirometry usually starts at 5 to 6 years. Forced vital capacity rises with growth while the boy is walking, peaks, plateaus and then falls; the age at which peak is reached and the rate of decline are predicted by the age at loss of ambulation, so regular measurement is essential.^[2]

Practical thresholds:

• Lung volume recruitment (manual bag or mechanical insufflation-exsufflation, once or twice daily) is indicated when forced vital capacity is 60% predicted or less.^[2]
• Assisted coughing (manual and mechanical) when forced vital capacity is under 50% predicted, peak cough flow is under 270 litres per minute, or maximum expiratory pressure is under 60 cm water.^[2]
• Nocturnal non-invasive ventilation when forced vital capacity is under 50% predicted, maximum inspiratory pressure below 60 cm water, symptoms of hypoventilation, or carbon dioxide above 45 mmHg or oxygen saturation under 95% on room air while awake.^[2]
• Sleep study abnormalities (carbon dioxide above 50 mmHg for at least 2% of sleep time, a sleep-related rise of 10 mmHg above awake baseline for over 2% of sleep time, oxygen saturation 88% or less for at least 2% of sleep time, or an apnoea-hypopnoea index of 5 or more per hour) also indicate nocturnal ventilation.^[2]
• Exercise with spirometry every 6 months; end-tidal or transcutaneous carbon dioxide every 6 months in all non-ambulatory patients.^[2]

Non-invasive ventilation is strongly preferred over tracheostomy, even up to 24 hours per day, with clear indications for tracheostomy reserved for patient preference, inability to use non-invasive ventilation, repeated failed extubations, or failed cough assistance with aspiration.^[2] Supplemental oxygen should not be used alone because hypoxaemia in DMD is usually due to hypoventilation, atelectasis or infection; 95% saturation is the practical line for increasing cough treatments.^[2] Vaccination against influenza and pneumococcus is part of routine care.^[2]

Cardiomyopathy eventually develops in most people with DMD. An electrocardiogram and imaging should establish a baseline, and echo is preferred until about 6 to 7 years, when cardiac MRI can usually be done without anaesthesia.^[2] Annual cardiac assessment is recommended, and at least annually after age 10 because the risk of left ventricular dysfunction rises.^[2]

ACE inhibitors or angiotensin receptor blockers are the traditional first-line therapy; guidance supports starting by about age 10 in boys with normal function, and starting drug therapy promptly once there is left ventricular dysfunction, myocardial fibrosis or symptoms.^[2] Beta blockers, mineralocorticoid receptor antagonists, and heart failure treatment then build on this. Preoperative imaging should precede scoliosis surgery. Arrhythmia surveillance should include Holter monitoring with the onset of abnormal left ventricular function or fibrosis.^[2]

Advanced options (ventricular assist devices, transplantation) exist but are highly selective.

Physiotherapy focuses on preventing contracture and preserving function: daily passive stretching of joints at risk, positioning and splinting, and submaximal aerobic activity such as swimming, while avoiding eccentric and high-resistance exercise.^[1] Functional testing (North Star Ambulatory Assessment, timed function tests, 6-minute walk distance) is performed every 6 months and should continue throughout life.^[1] Predictors of decline within 12 months include a 6-minute walk under 325 metres, taking over 30 seconds to stand, more than 8 seconds to climb four stairs, or a North Star score of 9 or less.^[1]

Foot and ankle surgery may improve gait, but hip and knee surgery in the ambulatory stage is not recommended.^[2] Scoliosis surveillance is annual; a curve over 20 degrees warrants orthopaedic review, and in the non-ambulatory patient a sitting curve of 20 to 30 degrees with growth remaining is an indication for posterior spinal fusion.^[2]

Management of Becker is the same package as Duchenne, tailored to a slower course: neuromuscular follow-up, rehabilitation to preserve muscle extensibility, cardiac surveillance (cardiomyopathy is the main danger and can occur in relatively strong patients), respiratory monitoring, bone health and bone protection, and agents addressing cardiomyopathy. Because Becker advances slowly, decisions about employment, reproduction and pacing of life can often be made with realistic hope.

There is no treatment that slows the molecular disease. Care is symptomatic and preventive, delivered by a team.^[6][7]

Muscle. Myotonia can be treated with the sodium channel blocker mexiletine, with lamotrigine as an alternative, although the cardiac safety profile in DM1 must be respected because conduction disease is common; both have small-trial evidence in DM1.^[6][7]

Cardiac. Evaluation at least annually for everyone, including a 12-lead ECG and pulmonary function tests; referral to a cardiologist familiar with DM1; 24-hour Holter monitoring and echocardiography every 2 to 5 years.^[6]

Respiratory. Regular forced vital capacity; referral if symptoms develop; polysomnography with carbon dioxide monitoring when nocturnal hypoventilation is suspected; some patients ultimately need nocturnal or continuous non-invasive positive-pressure ventilation.^[6] Annual influenza vaccination is recommended.^[6]

Other systems. Depending on symptoms, referral to ophthalmology (cataract), endocrinology (diabetes, thyroid, hormones), gastroenterology (dysphagia, pseudo-obstruction, constipation), rehabilitation, fertility services and mental health.^[6] Cognitive and emotional support is often crucial; many people with DM1 have reduced insight and lack of initiative, which makes proactive follow-up necessary rather than just offering appointments.^[6]

Perioperative care. People with DM1 have a higher risk of adverse reactions to anaesthetic and analgesic drugs. Any procedure needs advance planning with an anaesthetist familiar with the condition, following the international care recommendations.^[6]

Planning ahead. Because DM1 is a chronic progressive disease with shortened life expectancy (mean age at death in the mid-fifties, although this varies greatly), advanced care planning, including preferred place of care and resuscitation discussions, should be introduced early and revisited.^[6]

Multidisciplinary care is more complicated than it sounds: the symptoms are scattered across specialties, and several European and international consensus guidelines now exist to coordinate it.^[6]

DMD is now a condition with mutation-specific drugs in use or in late development. The main points to keep straight:

• Exon skipping uses antisense oligonucleotides (or gene therapy carrying small RNA) to bind pre-messenger RNA and skip a mutated exon, restoring the reading frame so a shorter but partly functional dystrophin is produced, like Becker. Candidate and approved drugs target exon 51 (eteplirsen, about 13 to 14% of patients; also drisapersen and SRP-5051), exon 53 (golodirsen and viltolarsen, about 8%), exon 45 (casimersen, about 9%), exon 44 (about 8%) and others.^[4][1]
• Eteplirsen (Exondys 51) received accelerated approval from the FDA in 2016 on the surrogate endpoint of increased dystrophin; the European Medicines Agency did not approve it. Golodirsen and casimersen followed by accelerated approval; viltolarsen was approved in 2020. Further trials (MIS51ON, ESSENCE, RACER53 and others) are running to confirm clinical benefit.^[4]
• Readthrough therapy. Ataluren (Translarna) promotes ribosomal readthrough of premature stop codons, targeting nonsense mutations in about 11 to 13% of patients. It received conditional marketing authorisation in Europe in 2014 for ambulatory patients aged 2 years and over. The FDA has not approved it, and confirmatory trials have not shown benefit in the primary endpoint.^[1][4]
• Gene replacement. Because the dystrophin gene is too large for a single adeno-associated virus, "microdystrophin" constructs are delivered by systemic AAV. Several (PF-06939926, SRP-9001/delandistrogene moxeparvovec, SGT-1001, GNT 0004) are in clinical trials, with NSAA change over about 1 year as a common primary endpoint. AAV delivery brings issues: pre-existing neutralising antibodies, immune responses (including myocarditis in early high-dose studies), and durability concerns because AAV rarely integrates into the genome.^[3][4]
• Other approaches. Vamorolone aims to keep anti-inflammatory effects without the usual steroid side-effect profile; idebenone (an antioxidant) failed its confirmatory respiratory trial; myostatin inhibitors, anti-fibrotic agents, stem and cardiosphere cell therapy, and utrophin modulation are all under study.^[4]

No gene therapy or antisense drug has cured DMD. The honest position is that care still rests on corticosteroids, rehabilitation, respiratory and cardiac support and bone health, with mutation-specific drugs as additions rather than replacements.

No disease-modifying therapy exists yet for DM1, but the pipeline is active.^[7] Because DM1 is a toxic RNA disease, most approaches target the RNA: antisense oligonucleotides that promote DMPK transcript degradation (including transferrin receptor-conjugated oligonucleotides such as del-desiran, in phase 2), small molecules that interfere with the toxic repeat (for example Tideglusib, a glycogen synthase kinase inhibitor, in paediatric congenital DM1), and metformin (in a phase 3 trial using muscle function as the endpoint).^[7] Gene editing remains preclinical. Myotonia in DM1 can be treated symptomatically with mexiletine.^[7]

DMD and BMD: cardiomyopathy and arrhythmia; respiratory failure and pneumonia; scoliosis; osteoporosis and fractures (including fat embolism after long-bone fracture); anaesthetic risk; obesity; early adult transition problems; (in some) cognitive and behavioural difficulties.^[1][2]

DM1: respiratory failure and sleep-disordered breathing (the commonest cause of death); sudden cardiac death (roughly 1% per year in adults); severe congenital perinatal mortality; endocrine disease; gastrointestinal dysmotility; cataracts; malignancy; anaesthetic complications; fertility problems. ^[6]

DMD prognosis has improved greatly with multidisciplinary care but the disease still shortens life. Wheelchair dependence is usually reached by about 12 years and assisted ventilation by about 20; death is most often from cardiac or respiratory failure, classically between 20 and 30 years. With modern care many live into their thirties and forties.^[3][4]

BMD is variable. Many affected men remain mobile through adulthood and, without heart or breathing problems, can have near-normal life expectancy.^[4]

DM1 is very heterogeneous. Some adults live an almost normal life; others lose ambulation and have shortened life expectancy from cardiorespiratory complications. Congenital DM1 has about 16% neonatal mortality from respiratory failure.^[6]

• Carrier detection and genetic counselling for families with DMD or DM1, including prenatal and preimplantation genetic diagnosis.^[1][6]
• Cardiac surveillance for carriers of DMD and for everyone with DM1.
• Annual (or more frequent) respiratory and cardiac monitoring in DM1.^[6]
• Eye examination for early cataract in unexplained family histories.
• Newborn screening for DMD (measuring creatine kinase from dried blood spots) is being revisited because of mutation-specific therapies, but DMD is not currently on standard newborn screening panels.^[1]
• DMD is not preventable, but complications are: steroid, respiratory, cardiac and bone-health programmes delay them.^[1][2]

• Children. DMD care should start early, before major decline; early glucocorticoids, nutrition and rehabilitation are beneficial.^[1] Intellectual disability and behavioural difficulties in congenital and childhood DM1 need assessment alongside motor concerns.^[6]
• Girls and women with DMD. Most are carriers with no or mild muscle symptoms but with a real risk of cardiomyopathy; they need baseline assessment in early adulthood and follow-up every 3 to 5 years.^[2]
• Pregnancy in DM1. Muscle, respiratory and cardiac involvement can complicate pregnancy and delivery; women need counselling about risk to the fetus (including congenital DM1) and multidisciplinary pregnancy care.^[6]
• Anaesthesia. Both DM1 and DMD carry serious anaesthetic risks (including malignant hyperthermia susceptibility concerns in DMD and respiratory/cardiac sensitivity in DM1). Any procedure needs specialist anaesthetic planning.^[6]

In DMD, the single most informative test is the creatine kinase, which is cheap and widely available: a massively raised level in a weak boy should trigger referral. Genetic testing may be unavailable locally; when it is, a muscle biopsy with immunohistochemistry or western blot can still confirm the diagnosis, although strong clinical suspicion and a raised creatine kinase are enough to start supportive and preventive care.^[1]

The care that changes outcomes is mostly low technology: daily stretching and positioning, safe physical activity, steroid prescribing with adrenal emergency kits, infection prevention (influenza and pneumococcal immunisation), cough techniques using a manual resuscitation bag, and non-invasive ventilation when forced vital capacity falls. Cardiac disease can be tracked with clinical examination, ECG and, where possible, echocardiography; ACE inhibitors or angiotensin receptor blockers can be started by age 10. Bone health monitoring can be done with spine radiographs. Referral pathways to a neuromuscular or paediatric centre should be established even if they are distant.^[1][2]

In DM1, diagnosis may follow from simple clues on examination (myotonia, ptosis, frontal balding, cataract, distal weakness) and a family history; CTG repeat testing may need to be sent to a reference laboratory. Annual ECG, pulmonary function testing and basic biochemistry (glucose, lipid profile, thyroid function) are the core of follow-up, with Holter and echocardiography when cardiac symptoms or ECG changes appear. Genetic counselling, including discussion of pregnancy risk, is essential even where advanced prenatal diagnosis is not available.^[6]

• DMD is an X-linked recessive, lethal dystrophin disorder with onset at 2 to 3 years, a very high creatine kinase, Gowers sign and calf pseudohypertrophy. ^[3]
• Becker is the milder allelic dystrophinopathy: some dystrophin is present, progression is slow, and many men remain ambulatory.
• DM1 is an autosomal dominant CTG repeat disorder (DMPK) with myotonia, distal weakness, ptosis and temporal wasting, frontal balding, cataracts, cardiac conduction disease and multi-system involvement.
• DMD diagnosis rests on genetic testing (deletion/duplication first, then sequencing, biopsy last); DM1 diagnosis rests on DMPK CTG repeat testing.
• Glucocorticoids are the main drug for DMD (deflazacort 0.9 mg/kg/day or prednisone 0.75 mg/kg/day typical), with adrenal emergency kits and careful monitoring of growth, bones and puberty.
• Respiratory, cardiac, nutritional and bone-health care should be anticipatory, starting before symptoms develop.
• Exon skipping (about 1 in 7 DMD cases, mainly amenable to exon 51 skipping), readthrough (nonsense mutations) and AAV microdystrophin gene therapy are in use or in trials, but none cures DMD.
• DM1 care is multidisciplinary, symptom-based and preventive, with annual cardiac and respiratory assessment. ^[6]

Musculoskeletal-skin and cardiology topics such as cardiomyopathy, cardiac arrhythmias, respiratory failure, osteoporosis, scoliosis, glaucoma and cataract, genetic counselling, and family planning may be linked once published. No other MedGrasp topic is linked from this page (prerequisites and related topics are none at present).