Becker muscular dystrophy

Published on 02/04/2015 by admin

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Last modified 22/04/2025

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88 Becker muscular dystrophy

Instruction

Examine this patient’s muscles.

Salient features

History

• Know whether there is a family history of the condition

• Age of onset

• Ask about shortness of breath (heart failure as a result of cardiomyopathy)

• History of mental retardation.

Examination

• 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.

Proceed as follows:

• Tell the examiner that you would like to check the IQ (mental retardation may be seen).

Diagnosis

This young patient has proximal muscle weakness and pseudohypertrophy (lesion) caused by Becker’s dystrophy (aetiology). The patient has mild disability and the condition is usually progressive (functional status).

Questions

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 usually between the ages of 5 and 15 years, but onset can occur in the third or fourth decades or even later. The majority survive into the fourth or fifth decades. Becker muscular dystrophy is less common (3 per 100 000 live male births) and has a more variable presentation of skeletal muscle weakness (Fig. 88.1).

image

Fig. 88.1 Distribution of predominant muscle weakness (shaded) in different types of dystrophy. (A) Duchenne and Becker types; (B) Emery–Dreifuss; (C) limb-girdle; (D) facioscapulohumeral; (E) distal; (F) oculopharyngeal.

Is there any difference between the genetics of Duchenne and Becker muscular dystrophy?

No, both Duchenne and Becker muscular dystrophy are caused by mutations in the same gene, located at Xp21. Dystrophin, its protein product, is usually absent in patients with Duchenne muscular dystrophy but is reduced in amount or abnormal in size in people with Becker muscular dystrophy. Another protein, utrophin, closely related to dystrophin, is encoded by a second gene on chromosome 6. In normal muscle, utrophin is located 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.

Advanced-level questions

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, even subclinical, myopathy, acanthocytosis and haemolytic anaemia. The definitive diagnosis rests on determination of the Kell red cell antigen phenotype

• Emery–Dreifuss muscular dystrophy, first described in a large family in Virginia by Emery and Dreifuss in 1966. Known association with deutan colour blindness led to localization of the gene on Xq28. The weakness presents in early childhood and is slowly progressive. The distribution of weakness is unique: an early humeral–peroneal pattern eventually evolves into a scapulo-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.

What is the role of antisense-mediated exon skipping in Duchenne’s muscular dystrophy?

Antisense-mediated exon skipping induces dystrophin synthesis in selected patients with Duchenne’s muscular dystrophy (N Engl J Med 2007;357:2677–86). The skipping of the additional exon restores the reading frame of the mRNA, allowing new production of dystrophin. The dystrophin that is produced is not normal but probably retains considerable function (as seen in patients with clinically milder Becker’s muscular dystrophy, who have similar or identically modified dystrophins).

What is the role of myogenic stem cell transplant in muscle degenerative disorders?

Prospectively isolatable muscle-forming stem cells are present in adult skeletal muscle and experimental studies have demonstrated the efficacy of myogenic stem cell transplant in therapy of muscle degenerative disease (Cell 2008;134:37–47). In particular, satellite cells reside beneath the basal lamina of skeletal muscle fibres and include cells that act as precursors for muscle growth and repair. Although they share a common anatomical localization and typically are considered a homogeneous population, satellite cells actually exhibit substantial heterogeneity. Cell-surface marker expression was utilized to purify from the satellite cell pool a distinct population of skeletal muscle precursors that function as muscle stem cells. When purified, these precursor cells were engrafted into muscle of dystrophin-deficient Mdx mice and were found to contribute up to 94% of myofibres, restoring dystrophin expression and significantly improving muscle histology and contractile function. Transplanted skeletal muscle precursors also entered the satellite cell compartment, renewed the endogenous stem cell pool and participated in subsequent rounds of injury repair.

Edward Meryon described Duchenne muscular dystrophy in 1852, 10 years before the French neurologist Guillaume Benjamin Amand Duchenne, with remarkably prescient pathological observations: ‘… the sarcolemma or tunic of the elementary fibre was broken and destroyed’ (Emery AEH, Emery MLH. The History of a Genetic Disease: Duchenne Muscular Dystrophy or Meryon’s Disease. London: Royal Society of Medicine Press, 1995).

PE Becker, Professor of Human Genetics at the University of Göttingen, Germany.

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 have known 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 large population study of Duchenne muscular dystrophy. Tony Murphy used the disease to develop bayesian risk-analysis procedures.

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