Résumé :
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In 1965, an adult-onset, autosomal dominant disorder with a peculiar scapuloperoneal distribution of weakness and atrophy was described in a large, multi-generation kindred and named 'scapuloperoneal syndrome type Kaeser'. By genetic analysis of the original kindred, a heterozygous missense mutation of the desmin gene R350P was discovered cosegregating with the disorder. Examination of 15 patients from 5 unrelated families harbouring R350P, including the original kindred described by Kaeser, showed large clinical variability, even within the same family, covering scapuloperoneal, limb girdle, and distal phenotypes with variable cardiac or respiratory involvement. While males do not have a higher overall incidence of cardiac or pulmonary involvement compared to females, risk for sudden death or fatal respiratory failure seems to be higher in males. Therefore, gender-related factors or modifier genes may be involved in determining disease onset and severity. Usually, desminopathies are diagnosed through muscle histology. Interestingly, histopathological examination of the biceps brachii muscle of the index patient from the original Kaeser family showed very limited myofibrillar changes or protein aggregation which was hardly demonstrated by desmin and filamin-c immunohistochemistry. Therefore, there is a wide morphologic spectrum of findings, ranging from near normal or unspecific pathology to typical, myofibrillar changes with accumulation of desmin. Mutations of the desmin gene should be considered early in the diagnostic work-up of any adult-onset, dominant myopathy with LGMD, distal, or scapuloperoneal phenotype, even if specific myofibrillar pathology is absent! So far, different diseases which may show a scapuloperoneal phenotype have been genetically identified: FSHD, IBMPFD due to VCP mutations, MFM due to mutations in DES, MYOT, FLNC, X-linked recessive myopathy due to FHL1 mutations, myosin storage myopathy due to MYH7 mutations, EDMD2/LGMD1B due to mutations in Lamin A/C, and the neurogenic Davidenkow's syndrome, allelic with HNPP due to a PMP22 deletion. However, the scapuloperoneal phenotype is not specific for these diseases, all forms can also present with predominant distal or limb-girdle involvement.
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