Rare syndromic craniosynostosis or isolated multisuture synostosis

Gene: TFAP2B

Comment on list classification: Changing rating from red to green as 4 cases have been reported.

Created: 17 Sep 2019, 12:06 p.m. | Last Modified: 17 Sep 2019, 12:06 p.m.

Panel Version: 1.133

4 cases reported
There are 4 cases reported in PMID: 31292255 (Correction in PMID: 31405973) 2 de novo and 2 inherited. There is evidence for reduced penetrance as in one case the variant was inherited from an unaffected parent.

Created: 17 Sep 2019, 12:05 p.m. | Last Modified: 17 Sep 2019, 12:05 p.m.

Panel Version: 1.130

Review from Helen Lord (Oxford University Hospitals NHS Trust):
Paper by Timberlake et al, 2019, PNAS, 116 (34) 17130 (PMID 31405973): 12 probands with syndromic craniosynostosis. Exome sequencing identified 4/12 TFAP2B variants – 3 of the patients had metopic synostosis and 1 had sagittal synostosis. 2 de novo (splicing and missense) and 2 rare transmitted LOF variants (nonsense variant (transmitted from an affected parent- looks like untreated metopic synostosis) and one affecting the initiating Met (transmitted from an unaffected parent)).

They comment that heterozygous damaging variants have been implicated in CHAR syndrome, and abnormal head shapes and ridging over the cranial sutures have been reported in several patients.

Created: 17 Sep 2019, noon | Last Modified: 17 Sep 2019, noon

Panel Version: 1.130

Gene suggested for inclusion by Helen Lord.
Sources: Expert Review

Created: 17 Sep 2019, 11:57 a.m.

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

Publications

• 31405973