Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Feb;188(2):692-707.
doi: 10.1002/ajmg.a.62536. Epub 2021 Oct 19.

Koolen-de Vries syndrome in a 63-year-old woman: Report of the oldest patient and a review of the adult phenotype

Marianna Farnè  1 , Laura Bernardini  2 , Anna Capalbo  2 , Giusy Cavarretta  3 , Barbara Torres  2 , Mariabeatrice Sanchini  1 , Sergio Fini  3 , Alessandra Ferlini  1   3 , Stefania Bigoni  3
Affiliations
Review

Koolen-de Vries syndrome in a 63-year-old woman: Report of the oldest patient and a review of the adult phenotype

Marianna Farnè et al. Am J Med Genet A. 2022 Feb.

Abstract

Koolen-de Vries syndrome (KdVS) is a rare genetic disorder caused by a de novo microdeletion in chromosomal region 17q21.31 encompassing KANSL1 or by a de novo intragenic pathogenic variant of KANSL1. KdVS is typically characterized by intellectual disability (ID), variable from mild to severe, developmental psychomotor delay, especially of expressive language development, friendly disposition, and multiple systemic abnormalities. So far, most of the individuals affected by KdVS are diagnosed in infancy or in adolescence; to the best of our knowledge, only 34 (including ours) adults have been reported in literature. Here we present the adult phenotype of a 63-year-old Italian woman affected by KdVS, caused by a 17q21.31 microdeletion. She is, to our knowledge, the oldest affected individual reported so far. We collected her clinical history and photographs, as well as those of other 26 adult patients described so far and compared her to them. We propose that the cardinal features of KdVS in adulthood are ID (ranging from mild to severe, usually moderate), friendly behavior, musculoskeletal abnormalities (especially scoliosis), and facial dysmorphism (a long face and a pronounced pear-shape nose with bulbous overhanging nasal tip). Therefore, we suggest considering KdVS in differential diagnosis in adult patients characterized by these features.

Keywords: 17q21.31 microdeletion; KANSL1; Koolen-de Vries syndrome; adult phenotype.

PubMed Disclaimer

Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

FIGURE 1
FIGURE 1
Photographs of our KdVS patient from infancy (a‐c) to adulthood (d‐f). (e and f) Show front and side profiles at last evaluation (62 years old): Narrow palpebral fissures and droopy eyelids became more evident as well as the broadening of the chin and a pronounced pear‐shaped nose. Notice in 1e a triangle‐shaped helix of the right ear, compared with the normal left ear in 1f
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

  • Genomic architecture and functional effects of potential human inversion supergenes.
    Campoy E, Puig M, Yakymenko I, Lerga-Jaso J, Cáceres M. Campoy E, et al. Philos Trans R Soc Lond B Biol Sci. 2022 Aug;377(1856):20210209. doi: 10.1098/rstb.2021.0209. Epub 2022 Jun 13. Philos Trans R Soc Lond B Biol Sci. 2022. PMID: 35694745 Free PMC article. Review.
  • Knockout mouse models as a resource for the study of rare diseases.
    da Silva-Buttkus P, Spielmann N, Klein-Rodewald T, Schütt C, Aguilar-Pimentel A, Amarie OV, Becker L, Calzada-Wack J, Garrett L, Gerlini R, Kraiger M, Leuchtenberger S, Östereicher MA, Rathkolb B, Sanz-Moreno A, Stöger C, Hölter SM, Seisenberger C, Marschall S, Fuchs H, Gailus-Durner V, Hrabě de Angelis M. da Silva-Buttkus P, et al. Mamm Genome. 2023 Jun;34(2):244-261. doi: 10.1007/s00335-023-09986-z. Epub 2023 May 9. Mamm Genome. 2023. PMID: 37160609 Free PMC article.

References

    1. Amenta, S. , Frangella, S. , Marangi, G. , Lattante, S. , Ricciardi, S. , Doronzio, P. N. , Orteschi, D. , Veredice, C. , Contaldo, I. , Zampino, G. , Gentile, M. , Scarano, E. , Graziano, C. , & Zollino, M. (2020). Adult phenotype in Koolen‐de Vries/KANSL1 haploinsufficiency syndrome. Journal of Medical Genetics, jmedgenet‐2020‐107225. 10.1136/jmedgenet-2020-107225 Epub ahead of print. - DOI - PubMed
    1. Bernardini, L. , Capalbo, A. , D'Avanzo, M. G. , Torrente, I. , Grammatico, P. , Dell'Edera, D. , Cavalcanti, D. P. , Novelli, A. , & Dallapiccola, B. (2007). Five cases of supernumerary small ring chromosomes 1: Heterogeneity and genotype‐phenotype correlation. European Journal of Medical Genetics, 50(2), 94–102. 10.1016/j.ejmg.2006.11.001 Epub 2006 Nov 23. - DOI - PubMed
    1. Ciaccio, C. , Dordoni, C. , Ritelli, M. , & Colombi, M. (2016). Koolen‐de Vries syndrome: Clinical report of an adult and literature review. Cytogenetic and Genome Research, 150(1), 40–45. 10.1159/000452724. Epub 2016 Nov 17 Decipher, https://decipher.sanger.ac.uk/patient/413465 - DOI - PubMed
    1. Dubourg, C. , Sanlaville, D. , Doco‐Fenzy, M. , Le Caignec, C. , Missirian, C. , Jaillard, S. , Schluth‐Bolard, C. , Landais, E. , Boute, O. , Philip, N. , Toutain, A. , David, A. , Edery, P. , Moncla, A. , Martin‐Coignard, D. , Vincent‐Delorme, C. , Mortemousque, I. , Duban‐Bedu, B. , Drunat, S. , … Andrieux, J. (2011). Clinical and molecular characterization of 17q21.31 microdeletion syndrome in 14 French patients with mental retardation. European Journal of Medical Genetics, 54(2), 144–151. 10.1016/j.ejmg.2010.11.003 Epub 2010 Nov 20. - DOI - PubMed
    1. Egger, J. I. , Wingbermühle, E. , Verhoeven, W. M. , Dijkman, M. , Radke, S. , de Bruijn, E. R. , de Vries, B. , Kessels, R. P. , & Koolen, D. (2013). Hypersociability in the behavioral phenotype of 17q21.31 microdeletion syndrome. American Journal of Medical Genetics. Part A, 161A(1), 21–26. 10.1002/ajmg.a.35652 Epub 2012 Nov 20. - DOI - PubMed

Substances

Supplementary concepts