KENNEDY DISEASE - GENETIC DIAGNOSIS OF AN INHERITED FORM OF MOTOR-NEURON DISEASE

Kennedy's disease (X-linked spinal and bulbar muscular atrophy) is an inherited form of motor neuron disease that may be diagnosed genetical ly using the polymerase chain reaction (PCR). This form of motor neuro n disease principally affects the proximal limb girdle muscles as well as those involved with deglutition and phonation. Onset is usually la te, in the fourth to fifth decades of life, and progression is slow. M oderate gynaecomastia and testicular atrophy are usually present, sugg esting a defect in androgen receptor function. Being inherited in an X -linked recessive manner, only males are affected, with females as the unaffected carriers. The genetic abnormality that causes Kennedy's di sease is an enlargement of the androgen receptor (AR) gene, which is l ocated on the proximal long arm of the X chromosome. In patients with this disease, a region in the gene containing repeated CAG triplet nuc leotides is approximately twice the size of that found in normal peopl e. Using PCR to amplify this region of the AR gene, this study confirm s this genetic mutation in 12 males from eight different families. All these families live on the east coast of Australia. This mutation was not found in five patients with other forms of motor neuron disease. Twelve heterozygote females, the daughters of affected males and carri er females, have also been identified. In addition, there are 14 asymp tomatic and as yet untested sons of carriers, ranging in age from less than one year to over 40 years of age. Each has a 50% chance of inher iting the abnormal gene from his mother and thus developing Kennedy's disease. This study shows that Kennedy's disease may be diagnosed gene tically using whole blood, and discusses the ethics of prenatal and pr esymptomatic testing, particularly in males under 16.