The Koolen-de Vries syndrome: A phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

David A. Koolen*, Rolph Pfundt, Katrin Linda, Gea Beunders, Hermine E. Veenstra-Knol, Essie H. Conta, Ana Maria Fortuna, Gabriele Gillessen-Kaesbach, Sarah Dugan, Sara Halbach, Omar A. Abdul-Rahman, Heather M. Winesett, Wendy K. Chung, Marguerite Dalton, Petia S. Dimova, Teresa Mattina, Katrina Prescott, Hui Z. Zhang, Howard M. Saal, Jayne Y. Hehir-KwaMarjolein H. Willemsen, Charlotte W. Ockeloen, Marjolijn C. Jongmans, Nathalie Van Der Aa, Pinella Failla, Concetta Barone, Emanuela Avola, Alice S. Brooks, Sarina G. Kant, Erica H. Gerkes, Helen V. Firth, Katrin Unap, Lynne M. Bird, Diane Masser-Frye, Jennifer R. Friedman, Modupe A. Sokunbi, Abhijit Dixit, Miranda Splitt, Mary K. Kukolich, Julie McGaughran, Bradley P. Coe, Jess Flórez, Nael Nadif Kasr, Han G. Brunner, Elizabeth M. Thompson, Jozef Gecz, Corrado Romano, Evan E. Eichler, Bert B.A. De Vries

*Corresponding author for this work
45 Citations (Scopus)


The Koolen-de Vries syndrome (KdVS; OMIM #610443), also known as the 17q21.31 microdeletion syndrome, is a clinically heterogeneous disorder characterised by (neonatal) hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism. Expressive language development is particularly impaired compared with receptive language or motor skills. Other frequently reported features include social and friendly behaviour, epilepsy, musculoskeletal anomalies, congenital heart defects, urogenital malformations, and ectodermal anomalies. The syndrome is caused by a truncating variant in the KAT8 regulatory NSL complex unit 1 (KANSL1) gene or by a 17q21.31 microdeletion encompassing KANSL1. Herein we describe a novel cohort of 45 individuals with KdVS of whom 33 have a 17q21.31 microdeletion and 12 a single-nucleotide variant (SNV) in KANSL1 (19 males, 26 females; age range 7 months to 50 years). We provide guidance about the potential pitfalls in the laboratory testing and emphasise the challenges of KANSL1 variant calling and DNA copy number analysis in the complex 17q21.31 region. Moreover, we present detailed phenotypic information, including neuropsychological features, that contribute to the broad phenotypic spectrum of the syndrome. Comparison of the phenotype of both the microdeletion and SNV patients does not show differences of clinical importance, stressing that haploinsufficiency of KANSL1 is sufficient to cause the full KdVS phenotype.

Original languageEnglish
JournalEuropean Journal of Human Genetics
Issue number5
Pages (from-to)652-659
Number of pages8
Publication statusPublished - 01.05.2016

Research Areas and Centers

  • Research Area: Medical Genetics


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