Rare syndromic craniosynostosis or isolated multisuture synostosis

Gene: IFT43

Red List (low evidence)

As reviewed by Tracy Lester and Rebecca Tooze, there is only one case is reported with craniosynostosis (PMID:21378380), while craniosynostosis was not reported as one of the clinical presentations in cases reported in PMIDs: 28400947 & 29896747. Hence, the rating should remain as RED.

Created: 12 May 2023, 1:01 p.m. | Last Modified: 12 May 2023, 1:01 p.m.

Panel Version: 4.73

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 21378380

I don't know

• A homozygous c.1A>G; p.(Met1Val) variant affecting the IFT43 gene was identified in an individual with anaemia and renal dysfunction, short stature, short limbs, brachydactylia, tooth agenesis, and retinal dystrophy, high-degree myopia, and chronic renal failure; it is not clear if this patient has craniosynostosis (Jia et al., 2018).
• Sequence analysis of candidate genes TTC8 and IFT43 in two affected siblings with Sensenbrenner syndrome revealed a homozygous variant in the translation initiation codon in exon 1 of IFT43 (c.1A>G; p.(?)); only the younger sibling displayed craniosynostosis (Arts et al., 2011).

Created: 2 Mar 2023, 1:29 p.m. | Last Modified: 2 Mar 2023, 1:29 p.m.

Panel Version: 3.4

I don't know

Cranioectodermal dysplasia type 3 ((Sensenbrenner syndrome) 614099: Characterised by skeletal abnormalities including CSS (OMIM). 2 sibs reported by Arts et al 2011: one with scaphocephaly and sagittal CSS, and one without craniofacial features. Short-rib thoracic dysplasia 18 with polydactyly -617866: Duran et al 2017 report 2 fetuses with short rib polydactyly syndrome: one with dolichocephaly and one with poor mineralization of the cranium. Phenotypic overlap with cranioectodermal dyplasia. Amber? Agree (AW) -CSS clearly documented in 1 of 2 in the Arts report, but not in the Duran cases. I tried to find more cases of IFT43 mutations by looking at citations to the Arts paper, but they seem to be rare. So I think amber more appropriate than green at the moment. ; Review on behalf of Tracy Lester and Andrew Wilkie

Created: 5 Mar 2019, 11:33 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cranioectodermal dysplasia type 3 - 614099; Short-rib thoracic dysplasia 18 with polydactyly -617866

I don't know

This gene 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; Gene symbol submitted: IFT43; Suggested initial gene rating: amber

Created: 5 Mar 2019, 11:21 a.m.