Koolen‐de Vries syndrome in the first adulthood patient of Southern India ancestry

Abstract

Koolen‐de Vries syndrome (KdVS, MIM#610443) is a rare malformation condition mainly characterized by cognitive impairment in association with craniofacial and visceral anomalies. The core phenotype is caused by mutations in the chromatin remodeler KANSL1 (MSL1V1, KIAA1267, KAT8 Regulatory NSL Complex Subunit 1, MIM#612452), which maps to 17q21.31 critical genomic region (Koolen et al., Nature Genetics 2012;44:639–641). Considering its molecular basis, KdVS is included in the group of Developmental Disorders of Chromatin Remodeling (DDCRs), also termed chromatinopathies. We describe the first KdVS patient of Southern India ethnicity, harboring the typical de novo 17q21.31 microdeletion, including KANSL1. Observed facial features and congenital anomalies are in line with the already reported KdVS phenotype, suggesting that phenotypic features are consistent across different ethnicities.

Spectrum of congenital anomalies of the kidney and urinary tract (CAKUT) including renal parenchymal malformations during fetal life and the implementation of prenatal exome sequencing (WES)

“…Life expectancy is not yet clearly defined; however, affected individuals usually reach adulthood. The prevalence of Koolen-de Vries syndrome is not fully investigated yet [ 45 – 47 ].…”

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

“…P1, present case P2 (Koolen et al, 2008) P3 (Dubourg et al, 2011) P4 (Terrone et al, 2012) P5 (Nascimento et al, 2017) P6 (Moreno-Igoa et al, 2015) P7 (Amenta et al, 2020) P8 (Amenta et al, 2020) P9 (Koolen et al, 2008;Shaw-Smith et al, 2006) Renal/urogenital anomalies Vesicoureteral reflux P12 (Amenta et al, 2020) P13 (Zollino et al, 2015) P14 (Pascolini et al, 2021) P15 (Koolen et al, 2006;Koolen et al, 2008) P16 (Koolen et al, 2016) P17 (Amenta et al, 2020) P18 (Zollino et al, 2015) P19 (Koolen et al, 2016) P12 (Amenta et al, 2020) P13 (Zollino et al, 2015) P14 (Pascolini et al, 2021) P15 (Koolen et al, 2006;Koolen et al, 2008) P16…”

“…In order to define an adult phenotype of KdVS, we searched for all the adult patients with KdVS in literature. We identified 34 (with ours included) adult individuals, of whom 15 are males (14 with a 17q21.31 microdeletion, one with a KANSL1 pathogenic variant) and 19 are females (16 with a 17q21.31 microdeletion, three with a KANSL1 pathogenic variant) (Amenta et al, 2020;Ciaccio et al, 2016;Dubourg et al, 2011;Koolen et al, 2006Koolen et al, , 2008Koolen et al, , 2016Moreno-Igoa et al, 2015;Morgan et al, 2018;Myers et al, 2017;Nascimento et al, 2017;Pascolini et al, 2021;Shaw-Smith et al, 2006;Terrone et al, 2012;Zollino et al, 2015). We have summarized the main clinical characteristics of 27 adult patients, having a full clinical description (Table 1).…”

“…We searched for them on PubMed, by using “Koolen‐de Vries syndrome,” “17q21.31 microdeletion,” and “ KANSL1 ” as keywords and selecting only patients who were at least 18‐year old at the time of clinical description. To the best of our knowledge, we identified 34 (with our patient included) adult patients, of whom 15 are males (14 with a 17q21.31 microdeletion, one with a KANSL1 pathogenic variant) and 19 are females (16 with a 17q21.31 microdeletion, three with a KANSL1 pathogenic variant) (Amenta et al, 2020 ; Ciaccio et al, 2016 ; Dubourg et al, 2011; Koolen et al, 2006 , 2008 , 2016 ; Moreno‐Igoa et al, 2015 ; Morgan et al, 2018; Myers et al, 2017 ; Nascimento et al, 2017 ; Pascolini et al, 2021 ; Shaw‐Smith et al, 2006 ; Terrone et al, 2012 ; Zollino et al, 2015 ). Since the clinical description of four adult patients in Myers et al ( 2017 ) and three in Morgan et al (2018) was more focused on epileptology and on speech development, respectively, we decided not to include these seven patients in the review (Table 1 , totally 27 patients were included).…”

“…Here we present an adult phenotype of a 63-year-old Italian woman affected by KdVS, who is, to our knowledge, the oldest affected individual reported so far in literature. Moreover, we searched for all the adult patients with KdVS in literature: we identified 34 (with our patient included) adult individuals, of whom 15 are males (14 with a 17q21.31 microdeletion, one with a KANSL1 pathogenic variant) and 19 are females (16 with a 17q21.31 microdeletion, three with a KANSL1 pathogenic variant) (Ciaccio et al, 2016;Dubourg et al, 2011;Koolen et al, 2006Koolen et al, , 2008Koolen et al, , 2016Moreno-Igoa et al, 2015;Morgan et al, 2018;Myers et al, 2017;Nascimento et al, 2017;Shaw-Smith et al, 2006;Terrone et al, 2012;Zollino et al, 2015;lastly, while concepting this manuscript, Amenta et al, 2020 andPascolini et al, 2021). In particular, we decided to collect the clinical characteristics of 27 (13 males and 14 females) out of 34 adult patients, excluding the seven patients (Morgan et al, 2018;Myers et al, 2017) whose clinical description was more focused on epileptology and on speech development respectively, in order to delineate the adult phenotype of this rare disease, which seems to be mainly characterized by ID, friendly behavior, musculoskeletal abnormalities, and facial dysmorphism.…”