Becker muscular dystrophy (DMD gene): later onset, heart care and inheritance

Becker and Duchenne muscular dystrophy are two ends of one spectrum. Both come from changes in the gene for dystrophin, a protein that stabilises the muscle cell membrane. In Becker the change is less damaging, so some dystrophin is made, though it is shortened or reduced. The NHS Genomics Education Programme explains that this accounts for the later onset, milder severity and slower progression compared with Duchenne.

People typically notice difficulty with walking, running, hopping and jumping, trouble climbing stairs, tiring easily with exercise, frequent falls or an unusual gait. Sometimes the first clue is a raised creatine kinase on a blood test done for another reason. The pattern is of gradually worsening weakness in the muscles around the hips and shoulders, but the programme says most people stay on their feet until adulthood.

The heart deserves particular attention. Dilated cardiomyopathy, electrical conduction problems and arrhythmia are described, and the programme says lifespan is often shortened by heart disease and respiratory complications, though most people with Becker survive into middle and older age.

Think of the dystrophin gene as a very long sentence. A deletion that removes a stretch of letters and keeps the remaining text readable in sets of three still produces a protein, only shorter; this is an in-frame change and typically causes Becker. A change that scrambles the reading of everything after it produces almost no working protein, and that is Duchenne. The NHS Genomics Education Programme says Duchenne results in less than 5% of normal dystrophin, while Becker variants are usually in-frame deletions or duplications, although splice and missense variants also occur.

This is also why the exact variant matters in clinic. Where genetic tests are negative, or the effect of a variant cannot be predicted but suspicion is high, specialist neuromuscular services may recommend a muscle biopsy with staining for dystrophin.

The gene sits on the X chromosome. A man with Becker passes his X chromosome to every daughter, who becomes a carrier, and a Y chromosome to every son, who does not inherit it from him. A carrier woman has a 1 in 2 chance of passing the changed X to each child, so each son has a 50% chance of being affected and each daughter a 50% chance of being a carrier.

The NHS Genomics Education Programme states that about half of cases are new in the person and half are inherited from the mother, and stresses the importance of establishing whether the mother carries the variant because the chances for future pregnancies depend on it. If a mother's blood does not show the variant, there remains a 20% chance of a future son being affected (5% for any future pregnancy overall) because of germline mosaicism.

Around 10% of female carriers of dystrophin variants have cardiac symptoms, so the programme recommends that carriers are assessed, not only counselled.

Diagnosis is based on the clinical picture, a raised creatine kinase and genomic testing where indicated. The NHS says that if you may have a child with muscular dystrophy, a GP can refer you to a genetic counsellor, and tests before, during and after pregnancy may include a carrier blood test, a blood test to check the baby's sex, chorionic villus sampling or amniocentesis, and a blood test after birth.

The programme adds that non-invasive prenatal diagnosis from about eight to nine weeks can determine fetal sex, with invasive testing for the family variant if the baby is male, and that prenatal or pre-implantation genetic diagnosis may be considered. It recommends counselling by the local clinical genetics team before conception.

The NHS Genomics Education Programme describes multidisciplinary care, commonly with a paediatric neurologist and a community paediatrician, bringing in respiratory, cardiac, orthopaedic and endocrine teams, physiotherapy, occupational therapy and psychosocial support. Experimental approaches such as gene therapy and exon skipping are being studied but are not yet available for routine use for Becker, according to the programme.

From the NHS: there is currently no cure for muscular dystrophy, but treatment can help symptoms, including physiotherapy, treatment for heart problems, surgery for scoliosis or tight joints, and breathing support if the lungs are involved. The NHS names Muscular Dystrophy UK, Pathfinders Neuromuscular Alliance and Duchenne UK among the organisations offering support.