Rare syndromic craniosynostosis or isolated multisuture synostosis
Region: ISCA-37420-Loss17q21.3 recurrent region (includes KANSL1) Loss
The required percent of overlap for this region has been changed from 80% to 60% and the genomic location has been updated inline with ClinGen following NHS Genomic Medicine Service approval.Created: 16 Mar 2022, 1:01 p.m. | Last Modified: 16 Mar 2022, 1:01 p.m.
Panel Version: 2.67
GMS Musculoskeletal test group informed of amber rating at Webex. No objections.Created: 17 Sep 2019, 12:33 p.m. | Last Modified: 17 Sep 2019, 12:33 p.m.
Panel Version: 1.133
Comment on list classification: Upgrading from red to amber as some evidence of association of the CNV loss with craniosynostosis. Will discuss on Webex with GMS Musculoskeletal test groupCreated: 6 May 2019, 11:04 a.m.
PMID: 26424144 - Zollino et al 2015 β 1 patient with craniosynostosis and 17q21.31 deletion (patient 28). Other patients with variants in KANSL1 but no craniosynostosis reported.
PMID: 21094706 - Dubourg et al 2011 β report 2 patients with Scaphocephaly and 17q21.31 deletion
PMID: 19447831 -Tan et al 2009 β KANSL1 called KIAA1267 in this paper. Five 17q21.31 deletion patients with phenotypes that include brachycephaly, dolichocephaly, scaphocephaly, positional plagiocephaly.Created: 16 Apr 2019, 1:33 p.m.
Review on behalf of Tracy Lester and Andrew Wilkie: Zollino report 2 cases with scaphocephaly or sagittal CSS.Created: 16 Apr 2019, 1:13 p.m.
This region 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; Region submitted: KANSL - del (17q21.21); Suggested initial rating: amberCreated: 16 Apr 2019, 1:09 p.m.
Phenotypes
Koolen-de Vries/KANSL haploinsufficiency syndrome.
Phenotypes for Region: ISCA-37420-Loss were changed from Koolen-de Vries/KANSL haploinsufficiency syndrome. to Koolen-De Vries syndrome, OMIM:610443; Developmental delay/intellectual disability, hypotonia, distinctive facial features, congenital malformations, and behavioural feature
GRCh38 position for ISCA-37420-Loss was changed from 45608879-46087510 to 45627800-46087514. Required Overlap Percentage for ISCA-37420-Loss was changed from 80 to 60.
Mode of inheritance for Region: ISCA-37420-Loss was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for Region: ISCA-37420-Loss were changed from to Koolen-de Vries/KANSL haploinsufficiency syndrome.
Publications for Region: ISCA-37420-Loss were set to
Region: isca-37420-loss has been classified as Amber List (Moderate Evidence).
Region: ISCA-37420-Loss was added Region: ISCA-37420-Loss was added to Craniosynostosis. Sources: NHS GMS Mode of inheritance for Region: ISCA-37420-Loss was set to