BRIEF COMMUNICATION Low yield in screening patients with sporadic motor neuron disease for Kennedy disease R. B. Saunderson, 1 B. Yu, 2,3 R. J. A. Trent 2,3 and R. Pamphlett 1 Departments of 1 Pathology (The Stacey MND Laboratory) and 2 Medicine, The University of Sydney and 3 Department of Molecular and Clinical Genetics, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia Key words motor neuron disease, Kennedy disease, amyotrophic lateral sclerosis, androgen receptor, CAG repeat, genetic testing. Correspondence Roger Pamphlett, Department of Pathology D06, The University of Sydney, Camperdown, NSW 2006, Australia. Email: rogerp@med.usyd.edu.au Received 27 November 2006; accepted 20 December 2006. doi:10.1111/j.1445-5994.2007.01499.x Abstract The diagnostic yield of testing for Kennedy disease in patients diagnosed with sporadic motor neuron disease (MND) is unclear. We measured the CAG repeat lengths in the androgen receptor gene of patients with progressive limb weak- ness who had either upper and lower motor signs (n = 130), or lower motor neuron signs alone (n = 30). Only one patient with a long history of lower motor weakness had a repeat length in the Kennedy disease range. Testing for Kennedy disease is unlikely to benefit MND patients with upper motor neuron signs or those with a short history of lower motor signs. Motor neuron disease (MND) describes a family of disor- ders that result from the degeneration of motor neurons in the brain and/or spinal cord. Amyotrophic lateral sclerosis (ALS), the most common form, affects both upper and lower motor neurons. Common lower motor neuron dis- orders in adults include progressive muscular atrophy (PMA) and spinobulbar muscular atrophy (Kennedy dis- ease) and the term lower MND (LMND) is used to describe this group. 1 The clinical features of progressive weakness, muscle atrophy and fasciculations are common to ALS and LMND. One problem in separating these forms of MND is the difficulty of showing subtle upper motor neuron signs and pyramidal tract degeneration is sometimes found at autopsy when it was clinically unapparent during life. 2 Kennedy disease is due to an expansion of the trinucle- otide CAG repeat in exon 1 of the androgen receptor gene (AR) on the long arm of the X-chromosome. 3,4 CAG repeat lengths normally range from 11 to 33 repeats but in Kennedy disease they vary from 38 to 62 repeats. 3,5 Expression of Kennedy disease is largely confined to men, although there have been reports of clinical mani- festations in female carriers. 4 Clinical features of Kennedy disease include mild sensory deficit, gynaecomastia, tes- ticular atrophy and infertility, features that are not found in other MND 6,7 Kennedy disease, however, may not be considered in the differential diagnosis of a motor neuron disorder when the classical features of the disease are lacking and may be misdiagnosed for other MND in both familial and sporadic MND patients. 8,9 This suggests that genetic screening of AR could be useful in patients with MND, given that the prognosis of Kennedy disease is more favourable than for most other MND. We, therefore, screened DNA for AR repeats in a group of Australian sporadic MND patients, including both the ALS and PMA forms, to see if any patients with Kennedy disease could be detected. Funding: This study was supported by the Motor Neuron Disease Research Institute of Australia and the Aimee Stacey MND Fund. The Australian MND DNA Bank is supported by the National Health and Medical Research Council. Potential conflicts of interest: None Internal Medicine Journal 37 (2007) 772–774 772 ª 2007 The Authors Journal compilation ª 2007 Royal Australasian College of Physicians