Résumé :
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It has previously been reported that about 8% of female carriers of Duchenne and Becker muscular dystrophy (DMD/BMD) present clinical signs of the condition. Wefollowed a cohort of genetically confirmed DMD/BMD manifesting carriers at the Newcastle neuromuscular centre for a mean of 8.5 years (range: 2-20 years). Respiratoryand cardiac functions were regularly reviewed and CK levels determined. Out of 323 DMD/BMD carriers, 26 patients showed clinical signs of the condition (18 DMD, 8BMD prevalence: 7.97%). Eleven did not have a family history of dystrophinopathy. Age of onset ranged from 2 to 52 years, 9/26 patients presented with symptomsin childhood (< 16 years). The main clinical presentation was proximal muscle weakness (15/26), affecting the lower limbs more than the upper limbs. Only 2 patientsbecame wheelchair bound in adulthood. Four patients presented with isolated dilated cardiomyopathy and did not develop skeletal muscle involvement at a mean ageof 49 years. 6 patients were referred to our clinic due to delayed cognitive and motor development; in half of them (3/6) there was no family history of dystrophinopathy.Although 5/6 developed muscle symptoms in their childhood, learning difficulties and behavioural problems remained the most prominent manifestation. One of thesepatients, aged 3 years, achieved normal motor milestones, but continued to show delayed speech development. CK levels were very high (> 1000 IU/L) in the majorityof patients, but normal in 4. Muscle biopsies were available from 7/11 sporadic patients and revealed a mosaic pattern of dystrophin and sarcoglycan expression. Nocorrelation between muscle pathology and clinical severity was observed. Dystrophin deletions were the most common mutations (17/26), followed by duplications(5/26) and point mutations (4/26). All patients presenting with cognitive impairment carried mutations in the distal part of the gene (exons 44-61). Because of therelative frequency of manifesting carriers, dystrophinopathies should be considered in the differential diagnosis of female patients with limb girdle weakness, as this mayhave important implications for genetic counselling. Developmental delay, learning difficulties or isolated cardiomyopathy were repeatedly observed phenotypes. Theyrepresent diagnostic challenges, particularly in the absence of a positive family history or missing muscle involvement.
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