Rare syndromic craniosynostosis or isolated multisuture synostosis
Gene: IRX5
Comment on list classification: As there are only two unrelated cases, this gene should be rated AMBER.Created: 12 May 2023, 1:23 p.m. | Last Modified: 12 May 2023, 1:23 p.m.
Panel Version: 4.78
PMID:22581230 - One family with three cases presenting with craniosynostosis.
PMID:29168297 - one case with craniosynostosis.
This gene has been associated with relevant phenotypes in both OMIM (MIM #611174) and Gene2Phenotype (with 'strong' rating in the DD panel).Created: 12 May 2023, 1:20 p.m. | Last Modified: 12 May 2023, 1:27 p.m.
Panel Version: 4.78
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Hamamy syndrome, OMIM:611174
Publications
• A heterozygous missense variant was identified in the Clarke cohort: c.1025C>T; p.(Thr342Ile) (Clarke et al., 2018).Created: 2 Mar 2023, 1:29 p.m. | Last Modified: 2 Mar 2023, 1:29 p.m.
Panel Version: 3.4
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bonnard et al 2012 report 2 families. In one family all 3 affecteds had CSS. Second case, and 2 brothers reported by Hamamy et al 2007, have brachycephaly. Knockdown in Xenopus embryos showed defective cranial NCC migration in first branchial arch. ; Review on behalf of Tracy Lester and Andrew WilkieCreated: 5 Mar 2019, 11:33 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Hamamy syndrome
Publications
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: IRX5; Suggested initial gene rating: amberCreated: 5 Mar 2019, 11:21 a.m.
Very rare; frequency of associated craniosynostosis uncertain. Mutations affect homeodomainCreated: 15 Sep 2015, 8:56 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Hamamy syndrome
Publications
Gene: irx5 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: IRX5 were changed from Hamamy syndrome to Hamamy syndrome, OMIM:611174
Publications for gene: IRX5 were set to 22581230
Source NHS GMS was added to IRX5.
This gene has been classified as Red List (Low Evidence).
This gene has been classified as Red List (Low Evidence).
IRX5 was added to Craniosynostosis syndromes phenotypespanel. Sources: Expert Review