Rare syndromic craniosynostosis or isolated multisuture synostosis

Gene: ZNF462

Green List (high evidence)

Agree with evidence below - promote to green gene

Created: 7 Jan 2022, 2:32 p.m. | Last Modified: 7 Jan 2022, 2:32 p.m.

Panel Version: 2.60

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

Phenotypes
Weiss Kruszka syndrome

Publications

• 28513610
• 31361404

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

Helen Lord review concurs with proposed green rating.

Created: 12 Jan 2022, 2:53 p.m. | Last Modified: 12 Jan 2022, 2:53 p.m.

Panel Version: 2.61

Comment on list classification: Promoting from grey to amber, but with a recommendation for green rating following GMS review. Metopic ridging or craniosynostosis reported in 6 cases with a plausible disease causing variant in ZNF462.

Created: 28 Jul 2021, 1:08 a.m. | Last Modified: 28 Jul 2021, 1:08 a.m.

Panel Version: 2.43

Associated with Weiss-Kruszka syndrome #618619 (AD) in OMIM.

PMID: 28513610 - Weiss et al 2017 - report 8 individuals from 6 families with predicted loss of function variants in ZNF462. They have overlapping phenotypes that include ptosis, metopic ridging, craniosynostosis, dysgenesis of the corpus callosum, and developmental delay. Metopic ridging or lambdoid craniosynostosis was noted in 5 of the 8 subjects (from 3 unrelated families). Family 1 had a nonsense variant that segregated in 4 family members with a variable phenotype. In all other families de novo variants or deletions (1.6 and 1.9 MB) in ZNF462 were found.

PMID: 31361404 - Kruszka et al 2019 - report an additional 14 individuals with loss of function variants in ZNF462. Most have some form of developmental delay, ptosis, down slanting palpebral fissures, exaggerated Cupid's bow/wide philtrum, and arched eyebrows. Metopic ridging or craniosynostosis was found in 3/14. In most cases the variant was found to be de novo.

Created: 28 Jul 2021, 1:06 a.m. | Last Modified: 28 Jul 2021, 1:06 a.m.

Panel Version: 2.40

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

Phenotypes
Weiss-Kruszka syndrome, OMIM:618619; weiss-kruszka syndrome, MONDO:0032836

Publications

• 28513610
• 31361404

Green List (high evidence)

Craniosynostosis observed in 38% of affected individuals.
Sources: Expert list

Created: 3 Jul 2020, 8:22 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Weiss-Kruszka syndrome, MIM# 618619

Publications

• 28513610

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