Rare syndromic craniosynostosis or isolated multisuture synostosis

Gene: IFT140

Green List (high evidence)

Comment on list classification: There is sufficient evidence (at least 3 cases) for this gene to be promoted to GREEN rating in the next GMS update.

Created: 12 May 2023, 12:26 p.m. | Last Modified: 12 May 2023, 12:26 p.m.

Panel Version: 4.72

PMID:22503633 - two cases from a single family with craniosynostosis, scaphocephaly and facial dysmorphy.
PMID:27874174 - single case with trigonocephaly and additional ciliopathy-related clinical features.
PMID:28288023 - single case with evolving craniofacial phenotype, striking brachydactyly and sensenbrenner syndromeand it was not clear if craniosynostosis was radiologically confirmed (as reviewed by Rebecca Tooze).
PMID:32007091 - single case with craniosynostosis and dolichocephaly.

Created: 12 May 2023, 12:25 p.m. | Last Modified: 12 May 2023, 12:25 p.m.

Panel Version: 4.71

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Short-rib thoracic dysplasia 9 with or without polydactyly, OMIM:266920

Publications

• 22503633
• 27874174
• 28288023
• 32007091

I don't know

• One male patient with distinctive clinical features of Sensenbrenner syndrome (dolichocephaly, shortening of long bones and early onset renal failure, ectodermal anomalies and small teeth was found to harbour a tandem duplication variant p.(Tyr1152_Thr1394dup) on one allele and a novel missense variant, p.(Leu109Pro), on the second allele (Walczak-Sztulpa et al., 2020).
• An individual with trigonocephaly and additional ciliopathy-related clinical features was found to harbour compound heterozygous variants in the IFT140 gene: a substitution at the splice donor site of exon 24 (c.723+1G>T; p.(?)) and a 17 bp deletion, impacting the first coding exon (c.-11_6del; p.(?)). These variants were confirmed by dideoxy-sequencing (Pena-Padilla et al., 2017).
• A patient was reported with brachydactyly (it is not clear if craniosynostosis was radiologically confirmed) and Sensenbrenner syndrome. Whole exome sequencing as part of the DDD study evidenced compound heterozygosity for IFT140: c.634G>A; p.(Gly212Arg) and c.2278C>T; p.(Arg760Ter) (Bayat et al., 2017).

Created: 2 Mar 2023, 1:28 p.m. | Last Modified: 2 Mar 2023, 1:28 p.m.

Panel Version: 3.4

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

I don't know

Phenotypic overlap with cranioectodermal dysplasia (IFT122 gene). Perrault et al 2012 report 2 patients from 1 family with CSS. Pena-Padilla et al 2017 report an infant with trigonocephaly. Amber/green - 3 cases but only 2 families? Added by GOSH - Bayat et al (2017) reported patient with evolving craniofacial phenotype, striking brachydactyly and sensenbrenner syndrome ; Review on behalf of Tracy Lester/Andrew Wilkie/GOSH

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

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Short-rib thoracic dysplasia with or without polydactyly; asphyxiating thoracic dysplasia (ATD,Jeune)

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 11 Oct 2023, 11:55 a.m. | Last Modified: 11 Oct 2023, 11:55 a.m.

Panel Version: 4.174

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: IFT140; Suggested initial gene rating: amber

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

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal