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

• Published in: Birth defects research Vol. 115; no. 5; pp. 563 - 571
• Main Authors: Lajmi, Yosra, Loeuillet, Laurence, Petrilli, Giulia, Egloff, Charles, Nectoux, Juliette, Molac, Clémence, Roux, Nathalie, Pannier, Emmanuelle, Achaiaa, Amale, Arkoub, Zaina Ait, Chuon, Sophie, Coussement, Aurélie, Dupont, Jean Michel, Malan, Valérie, Spaggiari, Emmanuel, Razavi, Ferechte, Amiel, Jeanne, Bessières, Bettina, Grotto, Sarah, Attié‐Bitach, Tania
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 15.03.2023
• Subjects: chylothorax; Comparative Genomic Hybridization; Female; FLT4 gene; Humans; hydrops fetalis; Hydrops Fetalis - diagnosis; Hydrops Fetalis - genetics; Lymphedema - congenital; Lymphedema - diagnosis; Lymphedema - genetics; lymphedema congenital type 1; Milroy disease; Mutation; Pregnancy; Ultrasonography, Prenatal; Vascular Endothelial Growth Factor Receptor-3 - genetics; hydrops fetalis; Milroy disease; lymphedema congenital type 1; FLT4 gene; chylothorax
• ISSN: 2472-1727; 2472-1727
• DOI: 10.1002/bdr2.2141

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.