Rinsho Shinkeigaku (Clinical Neurology)

Case Report

Two brothers with very late onset of muscle weakness in X-linked recessive spinal and bulbar muscular atrophy

Shoji Hemmi, M.D.1), Ken Inoue, M.D.2), Yumiko Kutoku, M.D.1), Mitsue Rikimaru, M.D.1), Tatufumi Murakami, M.D.1) and Yoshihide Sunada, M.D.1)

1)Department of Neurology, Kawasaki Medical School
2)Department of Neurology, Hiroshima Prefectural Hospital

Spinal and bulbar muscular atrophy (SBMA) is a motor neuron disease characterized by slowly progressive spinal and bulbar muscular atrophy associated with signs of androgen insensitivity including gynecomastia. This disease becomes prominent clinically in the fourth and fifth decades of life. Mutations of the androgen receptor (AR) gene associated with an expansion of CAG repeats is the cause of this disease. Here we report a unique family case in two brothers with SBMA with very late onset of muscular weakness.
Motor functional symptoms in the two brothers developed at the ages of 66 and 78 years. The number of CAG repeats in the AR gene in both patients was 42. According to previous reports, the number of CAG repeats is related to the age at onset of muscular weakness. Our patient's conditions were consistent with this concept as there was a short expansion of 42 CAG repeats linked to the clinical phenotype of very late onset of muscular weakness.
However, the issue of whether the number of CAG repeats is related to the age at onset of androgen insensitivity is still controversial. In the younger brother, gynecomastia appeared in his 20's and preceded the development of muscular weakness by about 40 years, whereas the gynecomastia in the older brother was unremarkable throughout his life. Our brother cases, which had the same number of CAG repeats and should share many common genetic factors, exhibited the androgen insensitivity differed. We therefore consider that an expansion of CAG repeats in the AR gene is not necessarily related to the age at onset of androgen insensitivity.
In conclusion, the etiologies of muscular weakness and androgen insensitivity in SBMA could be different.
Full Text of this Article in Japanese PDF (490K)

(CLINICA NEUROL, 49: 22－26, 2009)
key words: Spinal and bulbar muscular atrophy, androgen receptor gene, CAG repeats, muscular weakness, androgen insensitivity

(Received: 13-Mar-08)