Duchenne muscular dystrophy in a female with an X-autosome translocation

Abstract

Although Duchenne muscular dystrophy (DMD) is an X-linked disease, we report here a mild case of female DMD with a balanced X-autosome translocation. This is the first report in Japan as such a case. The patient is a 6-year old girl without any evidence of family history of DMD. She walked firstly at 14 months of age and her mental development had been normal. Between the age of 2 and 3 years, she was used to have muscle pain of her legs on exercise and could not run fast. Her calf muscles have been hypertrophic sine 3-4 years old. Her muscle pain and slight muscle weakness have been gradually improved. Physical examination at 6 years revealed slight muscle weakness with slight atrophy of left lower extremity, hypertrophy of calf muscles and pseudocontracture ankle joints. Diagnostic studies showed an extremely elevated CPK, and EMG and muscle biopsy consistent with DMD. Chromosome studies revealed an X-autosome translocation t(X;8) (p211;q243) in cultured lymphocytes, and the normal X-chromosome was late replicating in 80% of analyzed cells. Though mild clinical symptoms can be seen in female carriers of DMD, the patient with a clinical course as severe as that in male DMD has been rarely reported in females with X-chromosome aberration including structurally abnormal X-chromosome and X-autosome translocation. In such cases, DMD occurs from non-random Lyonisation, that is, selective inactivation of normal X-chromosome. Since Greenstein's report in 1977, 7 cases have been reported as female DMD with X-autosome translocation. Although different autosomes are involved, all these cases have a breakpoint at Xp21. Therefore, it is speculated that a DMD locus is at Xp21 and can be damaged by the translocation, giving rise to DMD. Though clinical symptoms of our case were mild compared with previously reported cases, this might be due to an incomplete non-random Lyonisation.