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Intellectual disability associated with craniofacial dysmorphism, cleft palate, and congenital heart defect due to a de novo MEIS2 mutation: A clinical longitudinal study
Author(s) -
Gangfuß Andrea,
Yigit Gökhan,
Altmüller Janine,
Nürnberg Peter,
Czeschik Johanna Christina,
Wollnik Bernd,
Bögershausen Nina,
Burfeind Peter,
Wieczorek Dagmar,
Kaiser Frank,
Roos Andreas,
Kölbel Heike,
ScharaSchmidt Ulrike,
Kuechler Alma
Publication year - 2021
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.62070
Subject(s) - intellectual disability , hypertelorism , exome sequencing , haploinsufficiency , missense mutation , medicine , genetics , scoliosis , pediatrics , phenotype , biology , anatomy , gene
Intellectual disability (ID) has an estimated prevalence of 1.5%–2%. Whole exome sequencing (WES) studies have identified a multitude of novel causative gene defects and have shown that sporadic ID cases result from de novo mutations in genes associated with ID. Here, we report on a 10‐year‐old girl, who has been regularly presented in our neuropediatric and genetic outpatient clinic. A median cleft palate and a heart defect were surgically corrected in infancy. Apart from ID, she has behavioral anomalies, muscular hypotonia, scoliosis, and hypermobile joints. The facial phenotype is characterized by arched eyebrows, mildly upslanting long palpebral fissures, prominent nasal tip, and large, protruding ears. Trio WES revealed a de novo missense variant in MEIS2 (c.998G>A; p.Arg333Lys). Haploinsufficiency of MEIS2 had been discussed as the most likely mechanism of the microdeletion 5q14‐associated complex phenotype with ID, cleft palate, and heart defect. Recently, four studies including in total 17 individuals with intragenic MEIS2 variants were reported. Here we present the evolution of the clinical phenotype and compare with the data of known individuals.