Giuseppe Noia1, Paolo Enrico Maltese2, Giuseppe Zampino3, Marco D'Errico4, Vittoria Cammalleri1, Paolo Convertini2, Giuseppe Marceddu5, Martina Mueller5, Giulia Guerri5, Matteo Bertelli2,5. 1. 1 Hospice Perinatale Centro per le Cure Palliative prenatali Santa Madre Teresa di Calcutta, Policlinico A. Gemelli-Centro Studi per la Tutela della Madre e del Concepito-Università Cattolica del Sacro Cuore-Roma, Roma, Italy. 2. 2 Magi's Lab, Rovereto, Italy. 3. 3 Centro Malattie Rare e Difetti Congeniti, Polo Scienza della Salute della Donna e del Bambino, Fondazione Policlinico Universitario A. Gemelli, Roma, Italy. 4. 4 Divisione di Ostetricia e Ginecologia, Ospedale "Cristo Re," Roma, Italy. 5. 5 Magi Euregio, Bolzano, Italy.
Abstract
BACKGROUND: The objective of this study is to examine the hypothesis that cystic hygroma (CH) with normal karyotype can manifest as a Mendelian inherited trait, and that a genetic similitude with hereditary lymphedema exists. To reach this goal, we investigated the prevalence of genetic variants in angiogenesis and lymphangiogenesis genes in a cohort of euploid fetuses with CH that almost resolved before delivery. A short review of cases from literature is also reported. METHODS AND RESULTS: Five fetuses were screened using a next-generation sequencing approach by targeting 33 genes known to be associated with vascular and lymphatic malformations. The genetic evaluation revealed two novel variants in KDR and KRIT1 genes. CONCLUSION: A review of the literature to date revealed that an association exists between CH and hereditary lymphedema and, similar to lymphedema, CH can be inherited in autosomal recessive and autosomal dominant manner, with the latter most likely associated with a better prognosis. About KDR and KRIT1 genes, no other similar associations are reported in the literature and caution is needed in their interpretation. In conclusion, we thought that a genetic test for the outcome of familial CH could be of enormous prognostic value.
BACKGROUND: The objective of this study is to examine the hypothesis that cystic hygroma (CH) with normal karyotype can manifest as a Mendelian inherited trait, and that a genetic similitude with hereditary lymphedema exists. To reach this goal, we investigated the prevalence of genetic variants in angiogenesis and lymphangiogenesis genes in a cohort of euploid fetuses with CH that almost resolved before delivery. A short review of cases from literature is also reported. METHODS AND RESULTS: Five fetuses were screened using a next-generation sequencing approach by targeting 33 genes known to be associated with vascular and lymphatic malformations. The genetic evaluation revealed two novel variants in KDR and KRIT1 genes. CONCLUSION: A review of the literature to date revealed that an association exists between CH and hereditary lymphedema and, similar to lymphedema, CH can be inherited in autosomal recessive and autosomal dominant manner, with the latter most likely associated with a better prognosis. About KDR and KRIT1 genes, no other similar associations are reported in the literature and caution is needed in their interpretation. In conclusion, we thought that a genetic test for the outcome of familial CH could be of enormous prognostic value.
Authors: Anna Letko; Alexandria Marie Schauer; Martijn F L Derks; Llorenç Grau-Roma; Cord Drögemüller; Alexander Grahofer Journal: Genes (Basel) Date: 2021-01-31 Impact factor: 4.096