Journal Article

Clinical delineation of SETBP1 haploinsufficiency disorder

Bernier, Raphael A, Whalen, Sandra, Jansen, Nadieh A, Quelin Chloé, Lesca Gaetan, van Bon Bregje W, Braden, Ruth O, Morgan, Angela T, Otness Erin F, van Haeringen Arie, Kleefstra Tjitske, Wong Maggie M K, Rossi, Massimiliano, Fisher, Simon E, Nizon Mathilde, Srivastava Siddharth

2021

Overview

SETBP1 haploinsufficiency disorder (MIM#616078) is caused by haploinsufficiency of SETBP1 on chromosome 18q12.3, but there has not yet been any systematic evaluation of the major features of this monogenic syndrome, assessing penetrance and expressivity. We describe the first comprehensive study to delineate the associated clinical phenotype, with findings from 34 individuals, including 24 novel cases, all of whom have a SETBP1 loss-of-function variant or single (coding) gene deletion, confirmed by molecular diagnostics. The most commonly reported clinical features included mild motor developmental delay, speech impairment, intellectual disability, hypotonia, vision impairment, attention/concentration deficits, and hyperactivity. Although there is a mild overlap in certain facial features, the disorder does not lead to a distinctive recognizable facial gestalt. As well as providing insight into the clinical spectrum of SETBP1 haploinsufficiency disorder, this reports puts forward care recommendations for patient management.

• Publisher: Nature Publishing Group
• Subject: Age / Chromosome 18 / Chromosomes / Gene deletion / Genes / Genetics / Genotype & phenotype / Haploinsufficiency / Hyperactivity / Intellectual disabilities / Patients / Pediatrics / Phenotypes / Speech