Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in the Netherlands: a cohort study

• Published in: The Lancet (British edition) Vol. 353; no. 9170; pp. 2116 - 2119
• Main Authors: Hoogerwaard, EM, Bakker, E, Ippel, PF, Oosterwijk, JC, Majoor-Krakauer, DF, Leschot, NJ, Van Essen, AJ, Brunner, HG, van der Wouw, PA, Wilde, AAM, de Visser, M
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 19-06-1999; Lancet; Elsevier Limited
• Subjects: Adolescent; Adult; Biological and medical sciences; Cardiomyopathy, Dilated - epidemiology; Cardiomyopathy, Dilated - etiology; Cohort Studies; Cross-Sectional Studies; Diseases of striated muscles. Neuromuscular diseases; Dystrophin - genetics; Dystrophy; Estimates; Female; Genetics; Heterozygote; Humans; Medical research; Medical sciences; Middle Aged; Muscle Weakness - epidemiology; Muscle Weakness - etiology; Muscular Dystrophies - epidemiology; Muscular Dystrophies - genetics; Muscular Dystrophies - physiopathology; Muscular dystrophy; Netherlands - epidemiology; Neurology; Netherlands; Europe; Human; Becker muscular dystrophy; Neuromuscular diseases; Nervous system diseases; Cardiomyopathy; Cardiovascular disease; Genotype; Medical screening; Genetic determinism; Myocardial disease; Genetic disease; Symptomatology; Phenotype; Association; Heart disease; Duchenne muscular dystrophy; Cohort study; Complication; Clinical investigation; Carrier
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(98)10028-4

Carriers of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) may show muscle weakness or dilated cardiomyopathy. Studies focusing on skeletal-muscle involvement were done before DNA analysis was possible. We undertook a cross-sectional study in a population of definite carriers to estimate the proportion and to assess the clinical profile of carriers with symptoms. We also assessed a possible correlation between genotype and phenotype.
Carriers of DMD and BMD, aged 18-60 years, were traced through the files of the central register kept at the Department of Human Genetics in Leiden, Netherlands. For each carrier who agreed to participate a medical history was taken, and muscle-strength assessment by hand-held dynamometry and manual muscle testing and cardiological assessment were done.
129 carriers of muscular dystrophy (85 DMD, 44 BMD) participated in the study. In 90 women from 52 (70%) families, 37 different mutations were found. 28 (22%) women had symptoms. 22 (17%) had muscle weakness, varying from mild to moderately severe. Muscle weakness was found in carriers of DMD and BMD, but dilated cardiomyopathy was found only in seven (8%) carriers of DMD, of whom one had concomitant muscle weakness. There was an unexpectedly high proportion of left-ventricle dilation (18%). No genotype-phenotype correlation was found.
Clinical manifestation of muscle weakness, dilated cardiomyopathy, or both can be found in about a fifth of carriers of DMD and BMD. If left-ventricle dilation is taken into account, the proportion of carriers with symptoms is even higher, amounting to 40%.