Novel Mutations and Unreported Clinical Features in KBG Syndrome.

Content Provider	Europe PMC
Author	Scarano, Emanuela Tassone, Martina Graziano, Claudio Gibertoni, Dino Tamburrino, Federica Perri, Annamaria Gnazzo, Maria Severi, Giulia Lepri, Francesca Mazzanti, Laura
Copyright Year	2019
Abstract	KBG syndrome is an autosomal dominant disorder caused by pathogenic variants within ANKRD11 or deletions of 16q24.3 which include ANKRD11. It is characterized by distinctive facial features, developmental delay, short stature, and skeletal anomalies. We report 12 unrelated patients where a clinical diagnosis of KBG was suspected and confirmed by targeted analyses. Nine patients showed a point mutation in ANKRD11 (none of which were previously reported) and 3 carried a 16q24.3 deletion. All patients presented with typical facial features and macrodontia. Skeletal abnormalities were constant, and the majority of patients showed joint stiffness. Three patients required growth hormone treatment with a significant increase of height velocity. Brain malformations were identified in 8 patients. All patients showed behavioral abnormalities and most had developmental delay. Two patients had hematological abnormalities. We emphasize that genetic analysis of ANKRD11 can easily reach a detection rate higher than 50% thanks to clinical phenotyping, although it is known that a subset of ANKRD11-mutated patients show very mild features and will be more easily identified through the implementation of gene panels or exome sequencing. Joint stiffness was reported previously in few patients, but it seems to be a common feature and can be helpful for the diagnosis. Hematological abnormalities could be present and warrant a specific follow-up.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6528090&blobtype=pdf
Page Count	9
ISSN	16618769
Volume Number	10
DOI	10.1159/000496172
PubMed Central reference number	PMC6528090
Issue Number	3
PubMed reference number	31191201
Journal	Molecular Syndromology [Mol Syndromol]
e-ISSN	16618777
Language	English
Publisher	Karger Publishers
Publisher Date	2019-01-15
Publisher Place	Switzerland
Access Restriction	Open
Rights License	Copyright © 2019 by S. Karger AG, Basel
Subject Keyword	ANKRD11 16q24.3 deletion Joint stiffness KBG syndrome Macrodontia
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical)