Non-syndromic familial congenital anorectal malformations

Gene: CDX2

Red List (low evidence)

Comment on list classification: 2 cases (conference abstract) plus functional evidence so rating Amber.

Created: 1 Nov 2018, 3:03 p.m.

Gao et al 2009 (PMID: 19386267) show that mice with Cdx2 ablated conditionally in the developing gut display severe hindgut abnormalities with a failure of colon development and a complete terminal blockage.

Tang et al 2016 (PMID: 27042391) show that CDX2 is expressed in the developing cloaca/hindgut in human embryos from weeks 4 to 9.

Created: 7 Oct 2018, 10:59 a.m.

Variants in CDX2 are reported to be associated with persistent cloaca in an abstract from Hsu et al 2018 from the Curating the Clinical Genome 2018 conference. From whole exome sequencing of 20 patients with perisitent cloaca and their unaffected parents novel p.Cys132* and p.Arg237His de novo CDX2 variants were identified in two unrelated patients. Not frequently found in ExAC, and the p.Arg237His variant is predicted to be in a DNA binding domain. Both variants altered the expression of CYP26A1, a direct CDX2 target encoding the major retinoic acid (RA)-degrading enzyme.

Created: 23 Aug 2018, 3:44 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
persistent cloaca