Duchenne muscular dystrophy (DMD gene): inheritance, carriers and care

Dystrophin is a protein that helps anchor muscle fibres to the surrounding framework and keeps the muscle cell membrane stable. Without it, muscle fibres are damaged and lost, and muscle is gradually replaced by fatty and fibrous tissue. The NHS describes muscular dystrophy as a genetic condition causing muscle weakness that gets worse over time, and names Duchenne as the most common type, which begins in early childhood, usually affects only boys, and progresses quickly.

The NHS Genomics Education Programme lists the early signs as delay in reaching motor milestones, toe-walking, frequent falls and a positive Gower sign, in which a child uses their hands to climb up their own legs to stand. The calves often look bulky, a feature called pseudohypertrophy, because muscle is replaced by fat and scar tissue. Blood levels of creatine kinase, an enzyme released from damaged muscle, are typically very high.

As the condition advances the heart is affected, typically from the mid-teens, with dilated cardiomyopathy and sometimes rhythm problems, and breathing muscles weaken. The programme also notes a recognised behavioural and cognitive profile: non-progressive intellectual disability in around 30% of boys, plus other neurodevelopmental and neurobehavioural differences. Life expectancy is reduced, usually because of heart and breathing complications.

DMD is one of the largest genes in the body. According to the NHS Genomics Education Programme, about 60% to 65% of Duchenne cases are caused by large out-of-frame deletions of one or more exons, about 10% by duplications, and the remaining 30% to 35% by nonsense, frameshift or splicing variants. All of these lead to a severely shortened protein that the cell breaks down.

Becker muscular dystrophy involves the same gene but in-frame changes that leave a shortened, partly working protein, which is why it is milder. This frame distinction is behind some of the newer treatments that depend on the exact variant, which is why the precise change is established in every family.

Boys have one X chromosome, so a single changed DMD gene is enough to cause the condition. Girls have two, and a girl with one changed copy is generally unaffected because the other copy works; she is a carrier. A son of a carrier mother has a 1 in 2 chance of Duchenne, and a daughter has a 1 in 2 chance of being a carrier. An affected man would pass his X chromosome to all of his daughters, who would be carriers, and to none of his sons.

Roughly one third of cases are new and two thirds are inherited, according to the NHS Genomics Education Programme. Even if the mother's blood shows no change, a later son still has about a 20% chance of being affected (about 5% for a future pregnancy overall) because of germline mosaicism, in which some of her egg cells carry the change although her blood does not. That is why the apparent absence of a family history does not remove the need for counselling.

Female carriers are usually unaffected, but the programme says they can have milder muscle weakness and up to 20% develop cardiac abnormalities, so carriers are advised to have heart checks.

A GP who suspects muscular dystrophy refers the child to a specialist; the NHS lists a blood test, a genetic test, electromyography, muscle biopsy and muscle MRI as tests that may be used. The NHS Genomics Education Programme says a molecular diagnosis is confirmed by finding a pathogenic variant in DMD, and a muscle biopsy with staining for dystrophin may help if genetic results are negative but suspicion remains high.

Families should be offered counselling by clinical genetics before another pregnancy. The NHS says tests in pregnancy may include a blood test to check whether a woman carries the altered gene, a blood test in early pregnancy to check the baby's sex, chorionic villus sampling or amniocentesis, and a blood test after birth. The programme adds that non-invasive fetal sexing can be done from about eight to nine weeks, with invasive testing for the family variant offered if the baby is male, and that pre-implantation genetic testing may be considered.

The NHS Genomics Education Programme describes care by a multidisciplinary team, commonly led by a paediatric neurologist, with respiratory, cardiac, orthopaedic and endocrine teams, physiotherapy, occupational therapy and psychosocial support. Corticosteroids form a key part of treatment. Newer therapies are being introduced or tested, and some depend on the exact genetic variant, but their availability on the NHS changes over time, so families should ask their neuromuscular team what applies to their child at present.

The NHS lists further support such as treatment for heart problems, surgery for scoliosis and tight joints, a breathing machine if the lungs are affected, mobility equipment, home adaptations and support at school and work. Muscular Dystrophy UK, Duchenne UK and Pathfinders Neuromuscular Alliance are the organisations the NHS names for support. Information about your child is passed to the National Congenital Anomaly and Rare Disease Registration Service, from which you can opt out at any time.