Dataset Information

KBG syndrome: Clinical features and molecular findings in seven unrelated Korean families with a review of the literature.

ABSTRACT:

Background

KBG syndrome is a rare genetic disorder involving macrodontia of the upper central incisors, craniofacial, skeletal, and neurologic symptoms, caused either by a heterozygous variant in ANKRD11 or deletion of 16q24.3, including ANKRD11. Diagnostic criteria were proposed in 2007 based on 50 cases, but KBG syndrome remains underdiagnosed.

Methods

Whole exome sequencing (WES) and array comparative genomic hybridization (array CGH) were conducted for genetic analysis and patient phenotypes were characterized based on medical records.

Results

Eight patients from seven unrelated families were confirmed with KBG syndrome. All patients (8/8, 100%) had some degree of craniofacial dysmorphism and developmental delay or intellectual disabilities. Triangular face, synophrys, anteverted nostril, prominent ears, long philtrum, and tented upper lip, which are typical facial dysmorphism findings in patients with KBG syndrome, were uniformly identified in the eight patients participating in this study, with co-occurrence rates of 4/8 (50%), 4/8 (50%), 4/8 (50%), 4/8 (50%), 5/8 (62.5%), and 5/8 (62.5%), respectively. Various clinical manifestations not included in the diagnostic criteria were observed. Six patients had point mutations in ANKRD11, one had an exonic deletion of ANKRD11, and one had a 16q24.3 microdeletion. According to the ACMG guidelines, all mutations were classified as pathogenic. The c.2454dup (p.Asn819fs*1) mutation in Pt 4 was reported previously. The remaining variants (c.397 + 1G>A, c.226 + 1G>A, c.2647del (p.Glu883Argfs*94), and c.4093C>T (p.Arg1365Ter)) were novel.

Conclusion

The clinical and molecular features of eight patients from seven unrelated Korean families with KBG syndrome described here will assist physicians in understanding this rare genetic condition.

SUBMITTER: Choi Y

PROVIDER: S-EPMC10094073 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

KBG syndrome: Clinical features and molecular findings in seven unrelated Korean families with a review of the literature.

Choi Yunha Y Choi Jungmin J Do Hyosang H Hwang Soojin S Seo Go Hun GH Choi In Hee IH Keum Changwon C Choi Jin-Ho JH Kang Minji M Kim Gu-Hwan GH Yoo Han-Wook HW Lee Beom Hee BH

Molecular genetics & genomic medicine 20221223 4

<h4>Background</h4>KBG syndrome is a rare genetic disorder involving macrodontia of the upper central incisors, craniofacial, skeletal, and neurologic symptoms, caused either by a heterozygous variant in ANKRD11 or deletion of 16q24.3, including ANKRD11. Diagnostic criteria were proposed in 2007 based on 50 cases, but KBG syndrome remains underdiagnosed.<h4>Methods</h4>Whole exome sequencing (WES) and array comparative genomic hybridization (array CGH) were conducted for genetic analysis and pat ...[more]

PMID: 36564961

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Project description:BackgroundPatients with KBG Syndrome due to ANKRD11 mutations and 16q24.3 microdeletions including ANKRD11 were identified. Classical and most frequent phenotypes include various degrees of intelligence disability (ID), short stature (SS), delayed bone age, macrodontia, distinctive facial features and skeletal anomalies. The variable expressivity of KBG syndrome makes it challenging to establish genotype-phenotype correlations, which also affects further studies for this novel syndrome. We aim to report three unrelated patients with KBG syndrome caused by ANKRD11 gene pathological variants and to evaluate potential associations among ANKRD11 gene variant types, the 16q24.3 microdeletion, and the clinical spectrum of KBG syndrome.MethodsThe genetic etiology of three unreported KBG patients was identified by whole exome sequencing and confirmed via Sanger sequencing. Literature review was conducted to summarize the phenotype-genotype relationship based on three unreported Chinese cases and 186 reported cases.ResultsTwo pathological variants (c.7407dupC, p.P2530Rfs*61; c.G3046A, p.D1016N) and one reported variant (c.6792dupC, p. P2271Pfs*8) were detected in our patients. Compared with the 16q24.3 microdeletion, patients harboring ANKRD11 gene mutations showed significantly higher frequency of malformations including macrodontia, long philtrum, abnormal eyebrows, widely spaced eyes, anteverted nares, eyelid ptosis, brachydactyly, brachycephaly (P<0.05), and significantly lower risk of congenital heart diseases and frontal bossing (P<0.05). The intellectual disability (ID) was significantly milder among patients carrying truncating variants located between repression domain 1 (RD1) and activation domain (AD) than those carrying mutations disrupting repression domain 2 (RD2) alone and disrupting all functional domain (RD1, AD or RD2) (P<0.05).ConclusionsNovel pathological variants harbored in the ANKRD11 gene contribute to the KBG syndrome variant spectrum. ANKRD11 gene variants disrupting RD1 and RD2 or RD2 alone are more likely to have more severe ID, which warrants different intervention strategies for KBG syndrome.

Dataset Information

KBG syndrome: Clinical features and molecular findings in seven unrelated Korean families with a review of the literature.

Background

Methods

Results

Conclusion

Publications

KBG syndrome: Clinical features and molecular findings in seven unrelated Korean families with a review of the literature.

Similar Datasets

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