Duchenne like muscular dystrophy in two sisters: evidence for autosomal recessive inheritance.

H.Somer, A.Salminen, S.Knuutila, and I.Kaitila, Departments of Neurology and Medical Genetics, University of Helsinki, Finland.

Duchenne muscular dystrophy is an X-linked disease with uniform clinical picture. The occurrence of a similar muscle disorder in girls has been observed occasionally, but Penn et al. (l), who re- viewed the literature, found little evidence for a separate entity: either the differential diagnosis against other neuromuscular di- seases was not unequivocal, or the condition could be explained by possible chromosomal abnormalities since adequate cytogenetic stu- dies were not always performed. More sophisticated chromosome techniques have recently revealed chromosomal translocations in the short arm of the X-chromosome in several cases ( 2 ) .

The patients are two sisters, now 16 and 19-years-old. Their pa- rents are first cousins, and the family has 12 children, seven boys and five girls. The patients are tenth and twelfth in order. The mother has eight sibs (three brothers and five sisters), and the father has 12 sibs (eight brothers and four sisters). No other member in the whole family shows signs of muscle disease.

Pregnancy and delivery were uneventful in both cases. During the first years of life they both showed normal developmental mile- stones except that they never learned to run properly. Difficulty in climbing stairs was detected between 6 and 7 years of age. Muscle weakness then progressed rapidly. When 10 years old they were unable to raise their upper extremities to the shoulder level or to get up from a chair. When confined to wheelchair at ages of 11 and 12 years they both had moderate contractures and severe scoliosis. At age of 15 they both were able to make slight move- ments with their fingers only.

Repeated clinical examinations have shown progressive muscular weakness involving also the facial muscles, pseudohypertrophy of the calves and normal intelligence. Their serum CK activity was 50

and 85 times the upper normal limit at the ages of 9 and 6 years, respectively. Muscle biopsy showed profound changes compatible with

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muscular dystrophy. Electromyography showed myopathic changes. Electrocardiography and 2-dimensional echocardiography showed no abnormality. Karyotypes studied by high-resolution banding technique on prometaphase chromosomes were normal.

The mother, now aged 60, has never shown signs of muscle disease. Her CK activity has been examined three times during the past ten years with two values slightly above the normal limit. Her muscle biopsy showed marginal changes with slightly increased fibre size variability and increased size of the nuclei. The ECG was normal. Serum CK determinations have been carried out in six sibs (four boys and two girls) and they showed slight elevations in three (1.5 - 4 x the upper normal limit), two others were marginal, and one was within normal range.

Despite sex the overall clinical picture, progression of the di- sease and the results of special investigations are indistinquish- able from X-linked Duchenne muscular dystrophy. The present results support the claim that there is a separate form of muscular dys- trophy inherited in an autosomal recessive way. This may explain the occurrence of Duchenne like illness in girls in some cases, when no chromosomal abnormalities are present.

The existence of a separate genetic entity simulating the clinical picture of Duchenne dystrophy has implications in research aimed to reveal the abnormal gene or t o identify the abnormal gene products. The erronous heterogeneity can be avoided only if cases w i t h con- firmed X-linked pedigree are utilized.

References: 1. Penn AS, Lisak RP and Rowland LP. Muscular dystrophy in young

girls. Neurology (Minneap) 1970: 20:147-159.

2. Jacobs PA, Hunt P A , Mayer M and Bart RD. Duchenne muscular dys-. trophy (DPlD) in a female with an X/autosome translocation : further evidence that the DMD locus is at Xp21. Am J Hum Genet 1981: 33:513-518.

3. Emery AE and Skinner R. Clinical studies in benign (Becker type) X-linked muscular dystrophy. Clin Genet 1976:10:189-201.