Clinical and genetic aspects of KBG syndrome.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620037
Title:
Clinical and genetic aspects of KBG syndrome.
Authors:
Low, K.; Ashraf, T.; Canham, N.; Clayton-Smith, J.; Deshpande, C.; Donaldson, A.; Fisher, R.; Flinter, F.; Foulds, N.; Fryer, A.; Gibson, K.; Hayes, I.; Hills, A.; Holder, S. E.; Irving, M.; Joss, S.; Kivuva, Emma; Lachlan, K.; Magee, A. C.; McConnell, V.; McEntagart, M. E.; Metcalfe, K.; Montgomery, T.; Newbury-Ecob, R.; Stewart, F.; Turnpenny, Peter D.; Vogt, J.; Fitzpatrick, D.; Williams, M.; Smithson, S.
Abstract:
KBG syndrome is characterized by short stature, distinctive facial features, and developmental/cognitive delay and is caused by mutations in ANKRD11, one of the ankyrin repeat-containing cofactors. We describe 32 KBG patients aged 2-47 years from 27 families ascertained via two pathways: targeted ANKRD11 sequencing (TS) in a group who had a clinical diagnosis of KBG and whole exome sequencing (ES) in a second group in whom the diagnosis was unknown. Speech delay and learning difficulties were almost universal and variable behavioral problems frequent. Macrodontia of permanent upper central incisors was seen in 85%. Other clinical features included short stature, conductive hearing loss, recurrent middle ear infection, palatal abnormalities, and feeding difficulties. We recognized a new feature of a wide anterior fontanelle with delayed closure in 22%. The subtle facial features of KBG syndrome were recognizable in half the patients. We identified 20 ANKRD11 mutations (18 novel: all truncating) confirmed by Sanger sequencing in 32 patients. Comparison of the two ascertainment groups demonstrated that facial/other typical features were more subtle in the ES group. There were no conclusive phenotype-genotype correlations. Our findings suggest that mutation of ANKRD11 is a common Mendelian cause of developmental delay. Affected patients may not show the characteristic KBG phenotype and the diagnosis is therefore easily missed. We propose updated diagnostic criteria/clinical recommendations for KBG syndrome and suggest that inclusion of ANKRD11 will increase the utility of gene panels designed to investigate developmental delay. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.
Citation:
Clinical and genetic aspects of KBG syndrome. 2016 Nov;170(11):2835-2846 Am. J. Med. Genet. A
Publisher:
Wiley
Journal:
American journal of medical genetics. Part A
Issue Date:
26-Sep-2016
URI:
http://hdl.handle.net/11287/620037
DOI:
10.1002/ajmg.a.37842
PubMed ID:
27667800
Additional Links:
http://dx.doi.org/10.1002/ajmg.a.37842
Note:
This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.
Type:
Journal Article
Language:
en
ISSN:
1552-4833
Appears in Collections:
Clinical Genetics (Peninsula Genetics); 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorLow, K.en
dc.contributor.authorAshraf, T.en
dc.contributor.authorCanham, N.en
dc.contributor.authorClayton-Smith, J.en
dc.contributor.authorDeshpande, C.en
dc.contributor.authorDonaldson, A.en
dc.contributor.authorFisher, R.en
dc.contributor.authorFlinter, F.en
dc.contributor.authorFoulds, N.en
dc.contributor.authorFryer, A.en
dc.contributor.authorGibson, K.en
dc.contributor.authorHayes, I.en
dc.contributor.authorHills, A.en
dc.contributor.authorHolder, S. E.en
dc.contributor.authorIrving, M.en
dc.contributor.authorJoss, S.en
dc.contributor.authorKivuva, Emmaen
dc.contributor.authorLachlan, K.en
dc.contributor.authorMagee, A. C.en
dc.contributor.authorMcConnell, V.en
dc.contributor.authorMcEntagart, M. E.en
dc.contributor.authorMetcalfe, K.en
dc.contributor.authorMontgomery, T.en
dc.contributor.authorNewbury-Ecob, R.en
dc.contributor.authorStewart, F.en
dc.contributor.authorTurnpenny, Peter D.en
dc.contributor.authorVogt, J.en
dc.contributor.authorFitzpatrick, D.en
dc.contributor.authorWilliams, M.en
dc.contributor.authorSmithson, S.en
dc.date.accessioned2016-10-14T11:12:26Z-
dc.date.available2016-10-14T11:12:26Z-
dc.date.issued2016-09-26-
dc.identifier.citationClinical and genetic aspects of KBG syndrome. 2016 Nov;170(11):2835-2846 Am. J. Med. Genet. Aen
dc.identifier.issn1552-4833-
dc.identifier.pmid27667800-
dc.identifier.doi10.1002/ajmg.a.37842-
dc.identifier.urihttp://hdl.handle.net/11287/620037-
dc.description.abstractKBG syndrome is characterized by short stature, distinctive facial features, and developmental/cognitive delay and is caused by mutations in ANKRD11, one of the ankyrin repeat-containing cofactors. We describe 32 KBG patients aged 2-47 years from 27 families ascertained via two pathways: targeted ANKRD11 sequencing (TS) in a group who had a clinical diagnosis of KBG and whole exome sequencing (ES) in a second group in whom the diagnosis was unknown. Speech delay and learning difficulties were almost universal and variable behavioral problems frequent. Macrodontia of permanent upper central incisors was seen in 85%. Other clinical features included short stature, conductive hearing loss, recurrent middle ear infection, palatal abnormalities, and feeding difficulties. We recognized a new feature of a wide anterior fontanelle with delayed closure in 22%. The subtle facial features of KBG syndrome were recognizable in half the patients. We identified 20 ANKRD11 mutations (18 novel: all truncating) confirmed by Sanger sequencing in 32 patients. Comparison of the two ascertainment groups demonstrated that facial/other typical features were more subtle in the ES group. There were no conclusive phenotype-genotype correlations. Our findings suggest that mutation of ANKRD11 is a common Mendelian cause of developmental delay. Affected patients may not show the characteristic KBG phenotype and the diagnosis is therefore easily missed. We propose updated diagnostic criteria/clinical recommendations for KBG syndrome and suggest that inclusion of ANKRD11 will increase the utility of gene panels designed to investigate developmental delay. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.en
dc.languageENG-
dc.language.isoenen
dc.publisherWileyen
dc.relation.urlhttp://dx.doi.org/10.1002/ajmg.a.37842en
dc.rightsArchived with thanks to American journal of medical genetics. Part A. This is an open access article under the terms of the Creative CommonsAttribution License, which permits use, distribution and reproduction inany medium, provided the original work is properly cited.en
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleClinical and genetic aspects of KBG syndrome.en
dc.typeJournal Articleen
dc.identifier.journalAmerican journal of medical genetics. Part Aen
dc.description.noteThis article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.en
dc.type.versionIn press (epub ahead of print)en

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