X-linked conditions

Box 4.6 X-linked conditions: examples

Duchenne muscular dystrophy Fragile X syndrome Haemophilia A and B

Box 4.7 X-linked conditions: key points

X-linked dominant

Females usually express disease.

Lethal in males.

Multiple miscarriages.

There is no male-to-male transmission. X-linked recessive Males are affected.

Females are usually affected less severely. There is no male-to-male transmission.

Duchenne muscular dystrophy

This hereditary muscular dystrophy is an X-linked recessive condition that affects males. It has an incidence of 1 in 3,500 males, with 1 in 2,500 females being carriers. It is characterised by a progressive muscle weakness that affects boys from the age of 3 to 5 years in 90% of cases. There is characteristic proximal muscle wasting and calf swelling, due to loss of muscle and its replacement by fat and connective tissue, resulting in affected boys being wheelchair bound by their early teens. The diagnosis should be considered in young boys when there is a developmental delay in speech or walking, with delays in motor milestones. Death commonly occurs before the second decade, due to cardiorespiratory failure.

The dystrophin gene that is found on the X chromosome is also transcribed in brain tissue, which accounts for learning difficulties in boys when there is alteration due to deletion of part of the gene. The protein produced by the gene is called dystrophin, and its absence leads to muscle cell degeneration.

Carriers of the altered gene can be biochemically tested by measuring creatinine kinase levels, which can be excessively high. Muscle biopsy can be diagnostic if DNA studies do not find an altered gene. However, DNA analysis together with creatinine kinase measurement will detect the majority of female carriers, and prenatal testing is available.

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