Rare syndromic craniosynostosis or isolated multisuture synostosis

Gene: ACTB

Green List (high evidence)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 5 Mar 2022, 6:18 p.m. | Last Modified: 5 Mar 2022, 6:18 p.m.

Panel Version: 2.65

Comment on list classification: Promoting from grey to amber, but with a recommendation for green rating following GMS review. There are more than 3 cases with plausible disease causing variants in this gene, and a relevant phenotype.

Created: 22 Jul 2021, 11:49 a.m. | Last Modified: 22 Jul 2021, 11:49 a.m.

Panel Version: 2.28

Associated with Baraitser-Winter syndrome 1 #243310 (AD) in OMIM.

More than 3 cases reported that include a craniosynostosis phenotype including:

PMID: 22366783 - Rivière et al 2012 - report 10 patients with Baraitser-Winter syndrome and variants in ACTB. 4 different missense variants were detected. In 4 cases they were shown to be de novo. No parental DNA was available in other cases. 8/10 showed trigonocephaly (metopic craniosynostosis). WES was used to screen initial trios and then targetted sequencing was used in further cases.

PMID: 23649928 - Johnston et al 2013 - report a 7 year old girl with atypical Baraitser-Winter syndrome-1 but whose features include metopic ridging. Exome analysis identified a de novo missense variant in ACTB, c.349G>A, p.E117K.

PMID: 23756437 - Donato et al 2014 - report 3 patients who had been diagnosed with Fryns-Aftimos syndrome and found that all 3 have different missense variants in the ACTB gene (targeted sequencing of ACTB and ACTG1). 1 had pansynostosis and 2 others were reported to have trigonocephaly. They reclassified the diagnosis of these patients as severe BRWS.

Created: 22 Jul 2021, 11:47 a.m. | Last Modified: 22 Jul 2021, 11:47 a.m.

Panel Version: 2.25

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Baraitser-Winter syndrome 1, OMIM:243310; Baraitser-Winter syndrome 1, MONDO:0009470

Publications

• 22366783
• 23649928
• 23756437

Green List (high evidence)

Ridged metopic suture is a key feature of this condition.
Sources: Expert list

Created: 2 Jul 2020, 10:26 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Baraitser-Winter syndrome 1, MIM# 243310