Cornelia de Lange syndrome (CdLS) is a malformation-retardation syndrome that typically presents with characteristic craniofacial dysmorphia, prenatal growth retardation, hypertrichosis, synophrys, reduction malformations of the upper extremities and intelligence impairment (average IQ: 53). In addition, heart defects and gastrointestinal disturbances are frequently found. In milder forms, which probably affect the majority of patients, the facial dysmorphia is milder than in the classic form; the cognitive impairment and limb defects are also less severe.
So far, pathogenic variants in 6 genes are known, whereby the largest proportion of variants are in the NIPBL gene (60%). In about 15-20% of patients with classic CdLS, NIPBL variants cannot be detected in peripheral lymphocytes because they are present in the mosaic in other tissues. In addition, variants are described in mosaic form in rare cases in the genes SMC3, RAD21 and SMC1A.
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