Spinal and Bulbar Muscular Atrophy Type Kennedy - AR

SBMA

Klinische Symptomatik

Spinal and bulbar muscular atrophy (SBMA) is a gradually progressive neuromuscular disorder in which degeneration of spinal and bulbar motor neurons results in proximal muscle weakness, muscle atrophy, and fasciculations. Affected men usually present with symptoms in their third to fourth decade. Frequently, intentional tremor, muscle cramps and endocrinologic disturbances (peripheral androgen resistance with reduced fertility and gynecomastia, diabetes mellitus) are observed. Bulbar symptoms (e.g. difficulties with speech articulation and swallowing) usually occur 10 to 20 years after onset of disease. CK levels are moderately elevated. Life expectancy usually is normal.

Genetik

Spinobulbar muscle atrophy is caused by an expanded CAG triplet repeat in the AR (androgen receptor) gene (Xq11-q12) and is inherited as X-linked recessive condition. Healthy control persons carry 9 to 36 CAG triplet repeats. Affected men carry 38 to 62 repeats. Whilst the disease manifests in men in adulthood, heterozyous female carriers (repeat expansion on only one X chromosome) are without symptoms and may transfer the disease on to their sons with a probability of 50%.

In contrast to other CAG repeat disorders, the number of repeats remains stable in the next generation. An expansion of the CAG repeats in the female germline is rare, and is mild in the male germline.

 

	Repeats
normal allele	< 35
pathological allele, reduced penetrance	35, 36, 37
pathological allele	> 37

Häufigkeit

1 : 50 000 in the male population

 

Diagnostik