X-CHROMOSOME MOSAICISM IN FEMALES WITH MUSCULAR DYSTROPHY

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Abstract
Muscular dystrophy often has an onset in the lower limbs in childhood and is usually inherited as a sex-linked recessive trait, occurring almost exclusively in boys. The abnormal gene is carried in the X-chromosome. A number of cases have been described in girls. A few of these may be explained by unusual genetic combinations, but it is difficult to explain them all in this manner. Measurements of serum levels of creatine phosphokinase (CPK) can detect all cases of juvenile dystrophy in the clinical or pre-clinical stages. This enzyme is also moderately elevated in the serum of most carrier mothers and about one half of female siblings, who presumably are also carriers. Since it has been recently shown that all human female somatic cells are distributed in a mosaical pattern, some with an active paternal X-chromosome and others with an active maternal X-chromosome, this hypothesis is evoked to explain both the CPK elevations and some of the cases of dystrophy in females. In the latter, the presumption is made that more maternal (defective) X-chromosomes are represented in the muscle fiber precursor cells than are normal paternal X''s. Muscle biopsies from three clinically normal female siblings with elevated CPK levels have shown pathology characteristic of muscular dystrophy in two of them. The pathology was spotty and focal, which was consistent with an admixture of two populations of muscle fibers, both normal and dystrophic. The genetic phenomenon of female X-chromosome mosaicism can explain all of the features noted. Hence, all, or nearly all, carrier heterozygous females have muscular dystrophy which is usually subclinical, due to the presence of an adequate complement of normal muscle fibers.