Adult phenotype in Koolen-de Vries/KANSL1 haploinsufficiency syndrome
- 24 December 2020
- journal article
- research article
- Published by BMJ in Journal of Medical Genetics
- Vol. 59 (2), 189-195
- https://doi.org/10.1136/jmedgenet-2020-107225
Abstract
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.Keywords
Funding Information
- Università Cattolica del Sacro Cuore (MIUR-University Grant D3.2, 2017)
- Fondazione Cassa di Risparmio di Lucca (year 2019)
- Associazione Kool Kids Kansl1 Italia (n/a)
This publication has 15 references indexed in Scilit:
- IntragenicKANSL1mutations and chromosome 17q21.31 deletions: broadening the clinical spectrum and genotype–phenotype correlations in a large cohort of patientsJournal of Medical Genetics, 2015
- The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variantEuropean Journal of Human Genetics, 2015
- A further contribution to the delineation of the 17q21.31 microdeletion syndrome: Central nervous involvement in two Italian patientsEuropean Journal of Medical Genetics, 2012
- Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndromeNature Genetics, 2012
- Mutations in KANSL1 cause the 17q21.31 microdeletion syndrome phenotypeNature Genetics, 2012
- Clinical and molecular characterization of 17q21.31 microdeletion syndrome in 14 French patients with mental retardationEuropean Journal of Medical Genetics, 2011
- Clinical and molecular delineation of the 17q21.31 microdeletion syndromeJournal of Medical Genetics, 2008
- Discovery of previously unidentified genomic disorders from the duplication architecture of the human genomeNature Genetics, 2006
- Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disabilityNature Genetics, 2006
- A new chromosome 17q21.31 microdeletion syndrome associated with a common inversion polymorphismNature Genetics, 2006