Examine this patient's muscles.
· Is there is a family history of the condition?· Age of onset.· Ask about shortness of breath (heart failure due to cardiomyopathy).· History of mental retardation.
Young adult male (>15 years).· Proximal weakness of the lower extremities (in later stages more generalized muscle involvement).· Pseudohypertrophy of calves.· Facial muscle weakness is characteristically absent or insignificant.· Kyphoscoliosis in late stages.Proceedasfo!lows:Tell the examiner that you would like to check the IQ(mental retardation may be seen).
This young patient has proximal muscle weakness and pseudohypertrophy (lesion) due to Becket's dystrophy (aetiology). Thepatient has mild disability and the con-dition is usually progressive (functional status).
What is the difference between Duchenne and Becker muscular dystrophy?
By definition, patients with Becker muscular dystrophy can ambulate beyond the age of 15 years. The onset in Becker is usuallybetween the ages of 5 and 15 years, but onset can occur in the third or fourth decades or even later. The majority survive into thefourth or fifth decades.
Is there any difference between the genetics of Duchenne and Becker muscular dystrophy?
No; both Duchenne and Becket muscular dystrophy are caused by mutations in the same dystrophin gene, located at Xp21. Anotherprotein, utrophin, closely related to dystrophin, is encoded by a second gene on chromosome 6. In normal muscle, utrophin islocated predominantly in the neuromuscular junction, whereas dystrophin is found in the sarcolemmal surface.
How would you confirm the clinical diagnosis of Becker dystrophy?
It requires Western blot analysis of muscle biopsy samples, demonstrating abnormal or reduced dystrophin.
Mention other X-linked myopathies.
· X-linked tubular myopathy, linked to Xq28.· McLeod syndrome, where the responsible gene has been localized to Xp21 and the phenotype is characterized by mild, evensubclinical, myopathy, acantho-cytosis and haemolytic anaemia. The definitive diagnosis rests on determination of the Kell redcell antigen phenotype.· Emery-Dreifuss muscular dystrophy, first described in a large family in Virginia by Emery and Dreifuss in 1966. Knownassociation with deutan colour blindness led to localization of the gene on Xq28. The weakness presents in early childhood andis slowly progressive. The distribution of weakness is unique: an early humeral-peroneal pattern eventually evolves into ascapulo-humero-pelvo-peroneal distribution. Marked focal atrophy of the humeral and peroneal muscles is a consistent feature.Pseudohypertrophy is absent, except in extensor digitorum brevis.P.E. Becker, Professor of Human Genetics at the University of Gbttingen, Germany.Edward Meryon described Duchenne muscular dystrophy in 1852, 10 years before the French neurologist Guillaume Benjamin Amand Duchenne, withremarkably prescient pathological observations: '... the sarcolemma or tunic of the elementary fibre was broken and destroyed' (Emery AEH, EmeryMLH 1995 The History of a Genetic Disease: Duchenne Muscular Dystrophy or Meryon's Disease).Duchenne is reported to have designed a version of the modern muscle biopsy needle which he kept in alcohol to prevent rusting. He could not haveknown that this also prevented sepsis.Newton Morton, a geneticist, was the first to introduce discriminant and segregation analysis into modern human genetics as a part of a largepopulation study of Duchenne muscular dystrophy. Tony Murphy used the disease to develop bayesian risk-analysis procedures.