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Review
. 2017 Dec 19;12(1):183.
doi: 10.1186/s13023-017-0736-8.

KBG syndrome

Dayna Morel Swols  1 , Joseph Foster 2nd  2   3 , Mustafa Tekin  4   5
Affiliations
Review

KBG syndrome

Dayna Morel Swols et al. Orphanet J Rare Dis. .

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.

Keywords: ANKRD11; KBG syndrome; Macrodontia; Review; Short stature.

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Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

Written informed consent was obtained from the patients or their guardian/parent/next of kin for the publication of this report and any accompanying images.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Craniofacial findings of KBG syndrome. (a, b, c) The same patient when he was 6 and 11 years old; (d) a 48-year-old patient. Note triangular face, synophrys, downslanting palpebral fissures, ptosis, high nasal bridge, anteverted nostrils, long philtrum, thin upper lip, and low anterior hairline
Fig. 2
Fig. 2
Macrodontia of permanent upper central incisors (a, b) Typical appearance of central upper incisors; (c) Prominent mamelons; (d) Slightly increased width of upper central incisors
Fig. 3
Fig. 3
Skeletal findings. (a) Accessory ribs; (b) Spina bifida occulta; (c, d):Clinodactyly
Fig. 4
Fig. 4
Location of reported causative variants in ANKRD11. Asterisks show location of recurrent variants, and y-axis gives reference for number of occurrences. From left to right these recurrent variants are as follows: NM_013275.5:c.1381_1384del (p.Glu461Glnfs*48), NM_013275.5:c.1801C > T (p.Arg601*), NM_013275.5:c.1903_1907del (p.Lys635Glnfs*26), NM_013275.5:c.2398_2401del (p.Glu800Asnfs*62), NM_013275.5:c.2408_2412del (p.Lys803Argfs*5), and NM_013275.5:c.3224_3227del (p.Glu1075Glyfs*242). The length of each line is proportional to the number of occurrences. ANK: Ankyrin repeat-containing domain (p.152–304). RD1: Repression Domain1 (p.318–611). Activation Domain (p.1851–2145). RD2: Repression Domain2 (p.2369–2663). Boundaries of exons are shown as alternating black and white boxes
See this image and copyright information in PMC

References

    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. doi: 10.1002/ajmg.a.31597. - DOI - PubMed
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MeSH terms

Supplementary concepts