Rare syndromic craniosynostosis or isolated multisuture synostosis

Gene: AXIN2

I don't know

Comment on list classification: As reviewed by Rebecca Tooze (University of Oxford), there is one case and supporting evidence from mouse models. Hence, this gene should be rated AMBER.

Created: 12 May 2023, 7:52 p.m. | Last Modified: 12 May 2023, 7:52 p.m.

Panel Version: 4.93

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
craniosynostosis, MONDO:0015469

Publications

• 15790973
• 30088857
• 30976280
• 34134783

• A heterozygous variant in AXIN2 was identified in a pair of twins and their father: c.1181G>A; p.(Arg394His). The variant has an allele frequency of 7.69e-4 – too common to be considered likely pathogenic (Xu et al., 2021).
• A child presenting with sagittal craniosynostosis was found to harbour a de novo loss-of-function variant in exon 4 of AXIN2 (c.1045_1046delCT; p.(Leu349fs*24)), which is absent from gnomAD. Alongside craniosynostosis, the patient displayed frontal bossing, high anterior hair line, depressed nasal bridge, bilateral epicanthus, and low set ears (Yilmaz et al., 2018).
• Animal models are available showing craniosynostosis (Lee et al., 2019)

Created: 2 Mar 2023, 1:17 p.m. | Last Modified: 2 Mar 2023, 1:17 p.m.

Panel Version: 3.4

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Red List (low evidence)

Yilmaz et al 2018 reported heterozygous frameshift variant NM_004655.3;c.1045_1046delCT, p.L349fs*24 in 3 year old patient with sagittal craniosynostosis. ; Review on behalf of GOSH/Tracy Lester

Created: 5 Mar 2019, 11:33 a.m.

Phenotypes
Oligodontia-colorectal cancer syndrome, 604025

I don't know

This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: AXIN2; Suggested initial gene rating: red

Created: 5 Mar 2019, 11:21 a.m.