Non-syndromic familial congenital anorectal malformations

Gene: RFX6

Comment on list classification: Rating this gene red as the observed gastrointestintal phenotypes are beyond the scope of the anorectal malformations panel

Created: 1 Nov 2018, 2:59 p.m.

Decision made with the Genomics England clinical team that the observed gastrointestintal phenotypes are beyond the scope of the anorectal malformations panel.

Created: 24 Oct 2018, 10:17 a.m.

Checking with Genomics England Clinical team if the observed phenotype associated with this gene is within the scope of this panel.

Created: 23 Oct 2018, 10:30 a.m.

RFX6 is associated with Mitchell-Riley syndrome in OMIM and MARTINEZ-FRIAS SYNDROME in Gene2Phenotype (confirmed). OMIM state that there is considerable phenotypic overlap between the two syndromes, the latter being characterized by the features of the Mitchell-Riley syndrome except for neonatal diabetes, and including tracheoesophageal fistula in some patients. Both syndromes include intestinal atresia as a major phenotype.

Smith et al. (2010) (PMID: 20148032) report 6 unrelated probands and Sansbury et al. (2015)(PMID:26264437) report 2 related patients (double first cousins) with plausible disease causing variants in RFX6 and Mitchell-Riley syndrome. All affected individuals show duodenal atresia. Some also show intestinal phenotypes such as jejunal atresia, intestinal malrotation, duodenal/jejunal web and Meckel's diverticulum.

Created: 16 Oct 2018, 9:09 a.m.

Comment on list classification: Rated gene Amber as is on expert list.

Created: 19 Sep 2018, 4:22 p.m.

Gene added from expert list from Dr Charles Shaw-Smith (Royal Devon and Exeter NHS Foundation Trust)

Created: 19 Sep 2018, 4:22 p.m.