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Cornelia de Lange syndrome (CdLS) is a multisystem disorder with variable expression marked by a characteristic facial dysmorphism, variable degrees of intellectual deficit, severe growth retardation beginning before birth (2nd trimester), abnormal hands and feet (oligodactyly, or sometimes an even more severe amputation, and constant brachymetacarpia of the first metacarpus), and various other malformations (heart, kidney etc.). The prevalence in the general population is estimated at between 1/62,500 and 1/45,000. Distinctive facial features include: well-defined curved and confluent eyebrows, long eyelashes, anteverted nares, micrognathia, and downturned corners of the mouth with a thin upper lip. Feeding problems and failure to thrive are frequently complicated by gastroesophageal reflux. Clinical progression leads to psychomotor retardation, language acquisition difficulties and, sometimes, behavioral disorders in the autistic spectrum. Hearing loss should be evaluated and monitored. Almost all cases are sporadic. Occasionally, familial transmission occurs, following an autosomal dominant pattern. Causative mutations in three genes involved in chromosomal cohesion (cohesin complex) have been identified. The NIPBL gene is mutated in approximately 50% of patients and is the major gene involved in the syndrome. Mutations associated with milder forms of the disease have recently been described in the SMC1L1 gene (also called SMC1A; Xp11.22-p11.21), associated with an X-linked form of CdLS, and in the SMC3 gene (10q25). Prenatal diagnosis may be suspected after a prenatal ultrasound examination revealing intrauterine growth retardation and limb defects. In families with parental transmission of the disease, and in which a mutation has been identified, prenatal diagnosis by analysis of fetal DNA can be proposed, even to parents who do not appear to carry the mutation because of the risk of germinal mosaicism. There is no cure for the disorder but psychoeducational care is necessary. The gastroesophageal reflux requires specific care, often gastrotomy and Nissen anti-reflux intervention.
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