Rare syndromic craniosynostosis or isolated multisuture synostosis
Gene: ALX4
Coronal CSS noted in 2 consanguineous families with AR FND2 (same mut) but NOT in a third family. CSS not a feature of AD PF. 2 inherited non-penetrant missense variants also seen in 2 unrelated cases with non-syndromic CSS. Suggested green status takes into account knowledge of several unpublished cases with CSS (AW) ; Review on behalf of Tracy Lester/Andrew WilkieCreated: 5 Mar 2019, 11:33 a.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Parietal foramina; Parietal foramina 2, (AD), 609597; Frontonasal dysplasia 2, (AR), 613451
Publications
Variants in this GENE are reported as part of current diagnostic practice
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: ALX4; Suggested initial gene rating: greenCreated: 5 Mar 2019, 11:21 a.m.
Comment on list classification: changed from Red to Green due to new evidence in the literature for craniosynostosisCreated: 13 Aug 2018, 4:19 p.m.
Comment on publications: Added publications El-Ruby et al., 2018 (PMID: 29681084) and Lee et al., (2017) PMID:29215649 to support upgrading of the gene to GreenCreated: 13 Aug 2018, 4:14 p.m.
Comment on phenotypes: added phenotype suggested by reviewer and OMIM relevant to the panelCreated: 13 Aug 2018, 4:12 p.m.
PMID: 29215649 and PMID:29681084
novel homozygous ALX4 mutation in two unrelated patients with frontonasal dysplasia type-2.Created: 13 Aug 2018, 4:05 p.m.
The Yagnik paper describes association with craniosynostosis and some functional evidence. Most heterozygous loss-of-function mutations in ALX4 cause parietal foramina, but association of craniosynostosis with particular mutations is feasible and supported by unpublished data from Wilkie labCreated: 14 Sep 2015, 1:57 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
parietal foramina
Publications
Source NHS GMS was added to ALX4. Rating Changed from Green List (high evidence) to Green List (high evidence)
Phenotypes for gene: ALX4 were set to Parietal foramina; Parietal foramina 2, (AD), 609597; Frontonasal dysplasia 2, (AR), 613451
Gene: alx4 has been classified as Green List (High Evidence).
Mode of inheritance for gene: ALX4 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ALX4 were set to 22829454; 29681084; 29215649
Publications for gene: ALX4 were set to 22829454; 29681084, 29215649
Phenotypes for gene: ALX4 were set to Parietal foramina; Parietal foramina 2, (AD), 609597; Frontonasal dysplasia 2, (AR), 613451
Phenotypes for gene: ALX4 were set to Parietal foramina; Parietal foramina 2, (AD) 609597; Frontonasal dysplasia 2, (AR) 613451
This gene has been classified as Red List (Low Evidence).
ALX4 was added to Craniosynostosis syndromespanel. Sources: Expert list