Cornelia de Lange Syndrome in a woman with mild phenotype and advanced age

Vilella, T., Furquim, I., Aoi, H., Matsumoto, M., Melaragno, M. I., Kim, A. E. (2025). Cornelia de Lange Syndrome in a woman with mild phenotype and advanced age (Version 1) [DataSet]. GestaltMatcher Database.

We present the case of a 47-year-old Brazilian woman who showed pre- and postnatal growth retardation, and neonatal jaundice. She presented the following craniofacial features: microcephaly, synophrys (childhood only), arched eyebrows, thin upper lip vermilion, downturned corners of the mouth, short neck, long philtrum, and narrow maxillary arch disproportionate to tooth size. Limb anomalies comprised symmetrical malformations including small hands, clinodactyly of the fifth finger, radioulnar synostosis, abnormal thumb implantation, 2-3 syndactyly, small feet, and shortening of the fourth and fifth toes. General findings included intellectual disability, pre- and post-natal short stature, arthrosis, and premature aging. She is the first child of a non-consanguineous healthy Brazilian couple. Exome sequencing revealed a de novo heterozygous splice site variant in the NIPBL gene (Aoi et al. 2019, 10.1038/s10038-019-0643-z), consistent with Cornelia de Lange Syndrome (CdLS). However, this patient exhibits higher cognitive and functional development than typically observed in CdLS, being literate, having worked in an office, and demonstrating well-developed speech. Furthermore, she has an unusually advanced age compared to most reported CdLS cases. In summary, the patient phenotype is mild. Although she displayed the classic feature of synophrys in childhood, this trait regressed with age. This case contributes to expanding the phenotypic spectrum of CdLS in adulthood.