Rare syndromic craniosynostosis or isolated multisuture synostosis

Gene: ALX4

Green List (high evidence)

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 Suggested green status takes into account knowledge of several unpublished cases with CSS (AW) ; Review on behalf of Tracy Lester/Andrew Wilkie

Created: 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

• 22829454
• 29681084
• 29215649

Variants in this GENE are reported as part of current diagnostic practice

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: ALX4; Suggested initial gene rating: green

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

Green List (high evidence)

Comment on list classification: changed from Red to Green due to new evidence in the literature for craniosynostosis

Created: 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 Green

Created: 13 Aug 2018, 4:14 p.m.

Comment on phenotypes: added phenotype suggested by reviewer and OMIM relevant to the panel

Created: 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.

Red List (low evidence)

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cause parietal foramina, but association of craniosynostosis with particular mutations is feasible and supported by unpublished data from Wilkie lab

Created: 14 Sep 2015, 1:57 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
parietal foramina

Publications

• 22829454