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Case Reports
. 2023 Mar 15;115(5):563-571.
doi: 10.1002/bdr2.2141. Epub 2022 Dec 20.

Two novel variations p.(Ser1275Thr) and p.(Ser1275Arg) in FLT4 causing prenatal hereditary lymphedema type 1

Yosra Lajmi  1 , Laurence Loeuillet  2 , Giulia Petrilli  2 , Charles Egloff  2 , Juliette Nectoux  1 , Clémence Molac  3 , Nathalie Roux  2 , Emmanuelle Pannier  4 , Amale Achaiaa  2 , Zaina Ait Arkoub  2 , Sophie Chuon  2 , Aurélie Coussement  1 , Jean Michel Dupont  1 , Valérie Malan  2 , Emmanuel Spaggiari  5 , Ferechte Razavi  2 , Jeanne Amiel  2 , Bettina Bessières  2 , Sarah Grotto  3 , Tania Attié-Bitach  2
Affiliations
Case Reports

Two novel variations p.(Ser1275Thr) and p.(Ser1275Arg) in FLT4 causing prenatal hereditary lymphedema type 1

Yosra Lajmi et al. Birth Defects Res. .

Abstract

Background: Hereditary lymphedema 1 is a rare congenital condition, characterized by the development of chronic swelling in body parts. It is highly variable in expression and age of onset with different presentations: from feet edema to hydrops fetalis. This affection is genetically heterogeneous with autosomal dominant inheritance and incomplete penetrance due to a mutation in the FLT4 gene in most cases.

Cases: In our study, we report on two fetuses harboring congenital lymphedema with FLT4 variation and review the prenatal confirmed ones of the literatures. Our cases were selected within fetuses explored by exome sequencing in a diagnosis setting. Prenatal ultrasonography showed hydrops fetalis in one case and an increased nuchal translucency with hydrothorax in the other. Comparative genomic hybridization array on amniocentesis was normal in both cases. Exome sequencing identified a variation p.(Ser1275Thr) and p.(Ser1275Arg) in fetus 1 and fetus 2 in the FLT4 gene, respectively. A de novo mutation at the same codon was reported in prenatal literature suggesting possible genotype phenotype correlation.

Conclusion: Cystic hygroma/hydrops fetalis are possible manifestations of several disorders. This study illustrates how the integration of exome sequencing in prenatal clinical practice can facilitate the diagnosis and genetic counseling of heterogeneous developmental affections.

Keywords: FLT4 gene; Milroy disease; chylothorax; hydrops fetalis; lymphedema congenital type 1.

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References

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