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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2017

Open Access 01-12-2017 | Review

KBG syndrome

Authors: Dayna Morel Swols, Joseph Foster II, Mustafa Tekin

Published in: Orphanet Journal of Rare Diseases | Issue 1/2017

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Abstract

Clinical Description

KBG syndrome is characterized by macrodontia of upper central incisors, distinctive craniofacial features such as triangular face, prominent nasal bridge, thin upper lip and synophrys; skeletal findings including short stature, delayed bone age, and costovertebral anomalies; and developmental delay/intellectual disability sometimes associated with seizures and EEG abnormalities. The condition was named KBG syndrome after the initials of the last names of three original families reported in 1975.

Epidemiology

The prevalence of KBG syndrome is not established. There are over 100 patients reported in the literature. It is likely that KBG syndrome is underreported due to incomplete recognition and very mild presentations of the disorder in some individuals. KBG syndrome is typically milder in females.

Etiology

Causative variants in ANKRD11 have been identified in affected individuals. The vast majority of identified variants are loss of function, which include nonsense and frameshift variants and larger deletions at 16q24.3. Haploinsufficiency appears to be the mechanism of pathogenicity.

Genetic Counseling

Familial and de novo cases have been reported. Causative de novo variants occur approximately one third of the time. Transmission follows an autosomal dominant pattern. The syndrome displays inter- and intra-familial variability.
Appendix
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Literature
1.
Skjei KL, Martin MM, Slavotinek AM. KBG syndrome: report of twins, neurological characteristics, and delineation of diagnostic criteria. Am J Med Genet. 2007;143A:292–300.CrossRefPubMed
2.
Goldenberg A, Riccardi F, Tessier A, Pfundt R, Busa T, Cacciagli P, et al. Clinical and molecular findings in 39 patients with KBG syndrome caused by deletion or mutation of ANKRD11. Am J Med Genet. 2016;170A:2847–59.CrossRef
3.
Low K, Ashraf T, Canham N, Clayton-Smith J, Deshpande C, Donaldson A, et al. Clinical and genetic aspects of KBG syndrome. Am J Med Genet. 2016;170A:2835–46.CrossRef
4.
Sirmaci A, Spiliopoulos M, Brancati F, Powell E, Duman D, Duman D, et al. Mutations in ANKRD11 cause KBG syndrome, characterized by intellectual disability, skeletal malformations, and Macrodontia. Am J Hum Genet. 2011;89:289–94.CrossRefPubMedPubMedCentral
5.
6.
Khalifa M, Stein J, Grau L, Nelson V, Meck J, Aradhya S, et al. Partial deletion of ANKRD11 results in the KBG phenotype distinct from the 16q24.3 microdeletion syndrome. Am J Med Genet. 2013;161A:835–40.CrossRefPubMed
7.
Miyatake S, Murakami A, Okamoto N, Sakamoto M, Miyake N, Saitsu H, et al. A de novo deletion at 16q24.3 involving ANKRD11 in a Japanese patient with KBG syndrome. Am J Med Genet. 2013;161A:1073–7.CrossRefPubMed
8.
Sacharow S, Li D, Fan YS, Tekin M. Familial 16q24.3 microdeletion involving ANKRD11 causes a KBG-like syndrome. Am J Med Genet. 2012;158A:547–52.CrossRefPubMed
9.
Herrmann J, Pallister PD, Tiddy W, Opitz JM. The KBG syndrome- a syndrome of short stature, characteristic facies, mental retardation, macrodontia and skeletal anomalies. Birth Defects Orig Artic Ser. 1975;11:7–18.PubMed
10.
Brancati F, D’Avanzo MG, Digilio MC, Sarkozy A, Biondi M, De Brasi D, et al. KBG syndrome in a cohort of Italian patients. Am J Med Genet. 2004;131A:144–9.CrossRef
11.
Kumar H, Prabhu N, Cameron A. KBG syndrome: review of the literature and findings of 5 affected patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;108:e72–9.CrossRefPubMed
12.
Lo-Castro A, Brancati F, Digilio MC, Garaci FG, Bollero P, Alfieri P, et al. Neurobehavioral phenotype observed in KBG syndrome caused by ANKRD11 mutations. Am J Med Genet Neuropsychiatr Genet. 2013;162B:17–23.CrossRef
13.
Zollino M, Battaglia A, D’Avanzo MG, Della Bruna MM, Marini R, Scarano G, et al. Six additional cases of the KBG syndrome: clinical reports and outline of the diagnostic criteria. Am J Med Genet. 1994;52:302–7.CrossRefPubMed
14.
Maegawa GH, Leite JC, Felix TM, da Silveira HL, da Silveira HE. Clinical variability in KBG syndrome: report of three unrelated families. Am J Med Genet. 2004;131A:150–4.CrossRef
15.
Oegema R, Schot R, de Wit MC, Lequin MH, Oostenbrink R, de Coo IF. Et al: KBG syndrome associated with periventricular nodular heterotopia. Clin Dysmorphol. 2010;19:164–5.CrossRefPubMed
16.
Novara F, Rinaldi B, Sisodiya SM, Coppola A, Giglio S, Stanzial F, et al. Haploinsufficiency for ANKRD11-flanking genes makes the difference between KBG and 16q24.3 microdeletion syndromes: 12 new cases. Eur J Hum Genet. 2017;25:694–701.CrossRefPubMedPubMedCentral
17.
Ashraf T, Irving M, Canham N, Holder S, Foulds N, Magee A, et al. KBG syndrome: a DDD front-runner? [abstract]. Eur Soc. Hum Genet. 2015;
18.
19.
20.
21.
Walz K, Cohen D, Neilsen PM, Foster J 2nd, Brancati F, Demir K, et al. Characterization of ANKRD11 mutations in humans and mice related to KBG syndrome. Hum Genet. 2015;164:181–90.CrossRef
22.
Neilsen PM, Cheney KM, Li CW, Chen JD, Cawrse JE, Schulz RB, et al. Identification of ANKRD11 as a p53 coactivator. J Cell Sci. 2008;121:3541–52.CrossRefPubMed
23.
Zhang A, Li CW, Chen JD. Characterization of transcriptional regulatory domains of ankyrin repeat cofactor-1. Biochem Biophys Res Commun. 2007;358:1034–40.CrossRefPubMedPubMedCentral
24.
Zhang A, Yeung PL, Li CW, Tsai SC, Dinh GK, Wu X, et al. Identification of a novel family of Ankyrin repeats containing cofactors for p160 nuclear receptor coactivators. J Biol Chem. 2004;279:33799–805.CrossRefPubMed
25.
Gallagher D, Voronova A, Zander MA, Cancino GI, Bramall A, Krause MP, et al. Ankrd11 is a chromatin regulator involved in autism that is essential for neural development. Dev Cell. 2015;32:31–42.CrossRefPubMed
26.
Barbaric I, Perry MJ, Dear TN, Rodrigues Da Costa A, Salopec D, Marusic A, et al. An ENU-induced mutation in the Ankrd11 gene results in an osteopenia-like phenotype in the mouse mutant Yoda. Physiol Genomics. 2008;32:311–21.CrossRefPubMed
27.
Reynaert N, Ockeloen CW, Savendahl L, Beckers D, Devriendt K, Kleefstra T, et al. Short stature in KBG syndrome: first responses to growth hormone treatment. Horm Res Paediatr. 2015;83:361–4.CrossRefPubMed
Metadata
Title
KBG syndrome
Authors
Dayna Morel Swols
Joseph Foster II
Mustafa Tekin
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2017
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-017-0736-8

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