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Original research
Adult phenotype in Koolen-de Vries/KANSL1 haploinsufficiency syndrome
  1. Simona Amenta1,
  2. Silvia Frangella1,
  3. Giuseppe Marangi1,2,
  4. Serena Lattante1,2,
  5. Stefania Ricciardi1,
  6. Paolo Niccolò Doronzio1,
  7. Daniela Orteschi2,
  8. Chiara Veredice3,
  9. Ilaria Contaldo3,
  10. Giuseppe Zampino4,5,
  11. Mattia Gentile6,
  12. Emanuela Scarano7,
  13. Claudio Graziano8,
  14. Marcella Zollino1,2
  1. 1Dipartimento Universitario Scienze della Vita e Sanità Pubblica, Sezione di Medicina Genomica, Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Roma, Italy
  2. 2Genetica Medica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
  3. 3Neuropsichiatria Infantile, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
  4. 4Dipartimento Universitario Scienze della Vita e Sanità Pubblica, Sezione di Pediatria, Università Cattolica Sacro Cuore, Facoltà di Medicina e Chirurgia, Roma, Italy
  5. 5Pediatria, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
  6. 6Genetica Medica, Dipartimento Materno-Infantile, Ospedale di Venere, Bari, Italy
  7. 7Dipartimento di Pediatria, Policlinico Universitario S. Orsola, Bologna, Italy
  8. 8Genetica Medica, Università di Bologna, Dipartimento Scienze Ginecologiche, Ostetriche e Pediatriche, Bologna, Italy
  1. Correspondence to Professor Marcella Zollino, Genetica Medica, Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Roma 168, Italy; marcella.zollino{at}


Background Koolen-de Vries syndrome (KdVS) is a multisystem neurodevelopmental disorder caused by 17q21.31 deletions or mutations in KANSL1. It was mainly described in children.

Methods A retrospective study on 9 subjects aged 19–45 years and revision of 18 literature patients, with the purpose to get insights into the phenotypic evolution with time, and into the clinical manifestations in adulthood.

Results Seven patients had a 17q21.31 deletion and two a point mutation in KANSL1. All had intellectual disability, which was mild in five (56%) and moderate in four (44%). Epilepsy was diagnosed in four subjects (44%), with onset from 1 to 7 years and full remission before 9 years in 3/4 patients. Scoliosis affected seven individuals (77.7%) and it was substantially stable with age in 5/7 patients, allowing for simple daily activities. Two subjects had severely progressive scoliosis, which was surgically corrected. Overweight or true obesity did occur after puberty in six patients (67%). Behaviour abnormalities were recorded in six patients (67%). The facial phenotype slightly evolved with time to include thick eyebrows, elongated nose and pronounced pointed chin. Despite behaviour abnormalities, happy disposition and sociable attitudes were common. Half of patients had fluent language and were good at writing and reading. Rich language, although limited to single words or short sentences, and very limited or absent skills in writing and reading were observed in the remaining patients. Autonomy in daily activities and personal care was usually limited.

Conclusions Distinctive features in adult KdVS subjects include intellectual disability, overweight/obesity, behaviour abnormalities with preserved social interest, ability in language, slight worsening of the facial phenotype and no seizures.

  • genetics
  • genotype
  • phenotype
  • epilepsy

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  • SA and SF contributed equally.

  • Correction notice This article has been corrected since it was published Online First. The affiliation of authors Simona Amenta, Silvia Frangella, Giuseppe Marangi, Serena Lattante, Stefania Ricciardi, and Paolo Nicolò Doronzio has been corrected. Also, Simona Amenta and Silvia Frangella contributed equally, and table 2 has been amended.

  • Contributors MZ planned the study, analysed clinical data, administered the questionnaire and wrote the manuscript. SA contributed to the writing of the MS, to the administering of the questionnaire and performed literature revision. SF, DO, SL, SR and PND performed genomic analyses and evaluation of genomic database and contributed to comparative evaluation of the genetic and the clinical data. CV and IC performed neurological evaluation and revision of brain MRI. GZ, MG, ES and CG contributed to the clinical evaluation and participated in patients’ recruitment. GM participated in writing the manuscript and in literature revision.

  • Funding This work was supported by a MIUR-University Grant D3.2, 2017; by Associazione Kool Kids Kansl1 Italia and by Fondazione Cassa di Risparmio di Lucca.

  • Competing interests None declared.

  • Patient consent for publication Parental/guardian consent obtained.

  • Ethics approval Institutional review board of DIPUSVSP, Protocol number 26-05-2080, Università Cattolica Sacro Cuore, Roma, Italy.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. Our data are not stored in a repository. They are all included in the article.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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