Noia Giuseppe, Maltese Paolo Enrico, Zampino Giuseppe, D'Errico Marco, Cammalleri Vittoria, Convertini Paolo, Marceddu Giuseppe, Mueller Martina, Guerri Giulia, Bertelli Matteo
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 Magi's Lab, Rovereto, Italy.
Lymphat Res Biol. 2019 Feb;17(1):30-39. doi: 10.1089/lrb.2017.0084. Epub 2018 Nov 22.
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.
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.
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.
本研究的目的是检验以下假设：核型正常的囊状水瘤（CH）可表现为孟德尔遗传性状，且与遗传性淋巴水肿存在遗传相似性。为实现这一目标，我们调查了一组在分娩前几乎消退的整倍体胎儿CH中血管生成和淋巴管生成基因的遗传变异患病率。还报告了对文献病例的简要回顾。
采用下一代测序方法对5例胎儿进行筛查，靶向33个已知与血管和淋巴管畸形相关的基因。基因评估发现KDR和KRIT1基因存在两个新变异。
迄今为止的文献综述显示，CH与遗传性淋巴水肿之间存在关联，并且与淋巴水肿类似，CH可呈常染色体隐性和常染色体显性方式遗传，后者最可能与较好的预后相关。关于KDR和KRIT1基因，文献中未报告其他类似关联，对其解读需谨慎。总之，我们认为对家族性CH的结果进行基因检测可能具有巨大的预后价值。
