Rare syndromic craniosynostosis or isolated multisuture synostosis
Gene: TRAF7
Castilla-Vallmanya et al, 2020 in the Supp table 1 they list the phenotypic information for all 45 patients. Craniofacial features are commnly observed in patients along with other features seen with this syndrome: patient 20 - bicoronal synostosis, patient 24 - mild sagittal synostosis, patient 43 lambdoid and saigittal synostosis. In addition patients 12,15,21,32,33 & 35 all have trigonocephaly and patients 16 and 30 have dolichocephaly. Tokita et al, 2018 - 7 unrelated individuals with het TRAF7 variants - all with overlapping features. In table S1 patient 2 has metopic synostosis and has a de novo het missense change. Patient 4 and 7 both have trigonocephaly and have different de novo missense changes. Patient 7 specifically mentions no craniosynostosis. 4 patients across these two papers with this syndrome who also have documented craniosynostosis.Created: 22 Jan 2021, 3:26 p.m. | Last Modified: 22 Jan 2021, 3:26 p.m.
Panel Version: 2.19
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
craniosynostosis
Publications
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 5 Mar 2022, 5:41 p.m. | Last Modified: 5 Mar 2022, 5:41 p.m.
Panel Version: 2.63
Both Andrew Wilkie and Helen Lord cite a publication that lists several patients with craniosynostosis and TRAF7 variants. Therefore this gene has a green rating recommendation for the next review.Created: 26 Jan 2021, 4:24 p.m. | Last Modified: 26 Jan 2021, 4:24 p.m.
Panel Version: 2.22
Comment on list classification: Promoting from grey to amber, but with recommendation for green rating following GMS review. Expert reviewer highlights more than 3 cases in which patients with variants in TRAF7 have a craniosynostosis phenotype.Created: 21 Jan 2021, 5:21 p.m. | Last Modified: 21 Jan 2021, 5:21 p.m.
Panel Version: 2.19
Castilla-Vallmanya et al (2020) reported the phenotypes associated with 45 heterozygous variants in TRAF7, missense mutations of which cause a recently recognised neurodevelopmental disorder. 3 of these individuals were reported to have craniosynostosis.
The submitter is aware of two additional unpublished cases with TRAF7 missense variants and craniosynostosis; one of these was missed in 100kGP by the GEL/GMC pipeline because TRAF7 was not included in PanelApp, the other is an unpublished case from Rotterdam.
In summary there appears to be sufficient evidence that craniosynostosis is a significant albeit low-frequency complication of pathogenic TRAF7 variants, which cause a complex neurodevelopmental disorder.
Sources: Expert ReviewCreated: 19 Jan 2021, 12:17 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
craniosynostosis
Publications
Tag for-review was removed from gene: TRAF7.
Source Expert Review Green was added to TRAF7. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag for-review tag was added to gene: TRAF7.
Gene: traf7 has been classified as Amber List (Moderate Evidence).
gene: TRAF7 was added gene: TRAF7 was added to Craniosynostosis. Sources: Expert Review Mode of inheritance for gene: TRAF7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TRAF7 were set to 32376980 Phenotypes for gene: TRAF7 were set to craniosynostosis Penetrance for gene: TRAF7 were set to Incomplete Review for gene: TRAF7 was set to GREEN