Fetal hydrops

Gene: FOXC2

Comment when marking as ready: Rated as green, and mode of inheritance complete.

Created: 19 Dec 2016, 10:30 a.m.

Comment on list classification: Updated rating from Grey to Green: FOXC2 added to panel by reviewer. Two green reviews (including review by submitter). Literature review shows >3 unrelated cases of FOXC2 mutations in cases of Lymphedema with Fetal hydrops. FOXC2 is a confirmed DD gene for Lymphedema-distichiasis syndrome (OMIM:153400).

Created: 15 Dec 2016, 3:39 p.m.

Comment on mode of inheritance: Mode of inheritance confirmed by OMIM and G2P.

Created: 15 Dec 2016, 3:33 p.m.

PMID:11078474 (Fang et al. 2000) report two families with dominantly inherited lymphedema (LD). Two children in one of the two initial families presented with severe in utero fetal hydrops. Fang et al., cloned FOXC2 as the responsible gene.

Created: 15 Dec 2016, 3:31 p.m.

PMID:21918810 (de Bruyn et al., 2012) describe a newborn girl, diagnosed with non-immune hydrops fetalis at a gestational age of 30 weeks. Family history revealed the presence of an autosomal dominant late-onset form of lymphedema of the lower limbs in her father. Genetic analysis in both the father and the newborn girl demonstrated a heterozygous FOXC2 mutation, c.939C>A, p.Tyr313X.

Created: 15 Dec 2016, 3:31 p.m.

PMID:25252123 (Sargent et al., 2014) describe a five generation family with dominantly inherited lymphedema (OMIM:153400), but no distichiasis, in which 3/3 affected offspring in the fifth generation have died of fetal hydrops and related birth defects. Mutational analysis disclosed a novel mutation in FOXC2 (R121C) in affected members.

Created: 15 Dec 2016, 3:31 p.m.

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Lymphedema-distichiasis syndrome; fetal hydrops

Publications

• 25252123
• 21918810

Green List (high evidence)

Also personal experience of hydrops in this condition

Created: 22 Nov 2016, 10:05 a.m.

Personal experience of fetal hydrops but most present after birth.

Created: 14 Nov 2016, 5:23 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
lymphoedema-distichiasis

Publications

• 25252123, 21918810