Fetal hydrops
Gene: FLT4Comment when marking as ready: Rated as green, and mode of inheritance complete.Created: 19 Dec 2016, 10:29 a.m.
Comment on mode of inheritance: Mode of inheritance confirmed by OMIM and G2P.Created: 15 Dec 2016, 3:11 p.m.
Comment on list classification: Updated rating from Grey to Green: FLT4 added to panel by expert. Two Green external reviews (one by submitter) plus >3 cases of FLT4 mutations in Lymphedema, hereditary, IA (OMIM:153100). FLT4 is a confirmed DD gene for OMIM:153100, which includes Fetal hydrops amongst symptoms.Created: 15 Dec 2016, 3:11 p.m.
PMID:16231305 (Daniel-Spiegel et al., 2005) report a case of primary congenital lymphedema (PCL) presenting as hydrops fetalis. The 39 year old Arab woman presented at 33(+4) weeks' gestation because of polyhydramnios. DNA analysis revealed a novel missense mutation, E1106K, in the tyrosine kinase domain of the vascular endothelial growth factor receptor 3 gene (FLT4, also known as VEGFR3).Created: 15 Dec 2016, 3:06 p.m.
Non-immune fetal hydrops is a rare prenatal manifestation of Lymphedema, hereditary, IA (LMPH1A, OMIM:153100). >3 cases of heterozygous FLT4 mutations recorded in LMPH1A/OMIM:153100 including rs121909654 (2632G-A transition resulting in a V878M substitution) in a 22-week old fetus who was found to have fetal hydrops with bilateral leg edema, pleural effusions, hydrothorax, and pulmonary hypoplasia (identified in PMID:16965327). PMID:16965327 (Ghalamkarpour et al., 2006) state that FLT4 screening should be added to the investigation of cases of hydrops fetalis of an unknown etiology.Created: 15 Dec 2016, 3:01 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Lymphedema hereditary IA; fetal hydrops
Publications
Also personal experience of hydrops in this conditionCreated: 22 Nov 2016, 10:03 a.m.
Personal experience of fetal hydrops but most present after birth.Created: 14 Nov 2016, 5:22 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Hereditary lymphoedema type 1a
Publications
21 December 2016. External reviews were assessed, and panel was revised according to expert review, internal discussion and additional curation. Following internal discussion, all genes from the V1.14 'RASopathies' panel were added as green EXCLUDING NF1 and SPRED1- a cautious approach was taken because Fetal hydrops is a fetal panel. All relevant genes from the 'Mucopolysaccharideosis, Gaucher, Fabry' V1.0 panel (lysosomal storage disorders) were also added to the Fetal hydrops panel as green together with genes from the literature where there is a reasonable link between the corresponding lysosomal storage disorder (LSD) and Fetal hydrops. All PEX genes from the V1.2 'Peroxisomal disorders' panel were added as green based on a link between peroxisomal biogenesis disorders and Fetal hydrops.
This gene has been classified as Green List (High Evidence).
Publications for FLT4 were set to 16231305; 16965327
Mode of inheritance for FLT4 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
This gene has been classified as Green List (High Evidence).
Mode of inheritance for FLT4 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for FLT4 were set to Lymphedema, hereditary, IA, 153100; Hereditary lymphoedema type 1a; fetal hydrops
FLT4 was added to Fetal hydropspanel. Sources: Literature,Other
FLT4 was created by dgw