Table1_Case report: Prenatal diagnosis of Ectrodactyly–Ectodermal dysplasia–Cleft syndrome (EEC) in a fetus with cleft lip and polycystic kidney.docx

Ectrodactyly–ectodermal dysplasia–cleft (EEC) syndrome is an autosomal dominant disorder characterized by ectrodactyly, ectodermal dysplasia, and orofacial clefting. Reduced penetrance is manifested in these core features and additional under-recognized features, especially in prenatal cases. Here, we present a fetus with EEC syndrome at 22 weeks gestation, in which the cleft lip and palate and the right polycystic kidney are shown by prenatal ultrasound. A de novo missense mutation of R304W in the TP63 gene is confirmed by whole-exome sequencing associated with EEC syndrome. We further investigate the reported TP63-related prenatal cases and provide a more complete picture of the prenatal phenotypic spectrum about EEC. It illustrates the potential severity of genitourinary anomalies in TP63-related disorders and highlights the need to counsel for the possibility of EEC syndrome, given the occurrence of genitourinary anomalies with orofacial cleft or limb deformities.

外胚层发育不良-唇腭裂-缺指（趾）综合征（Ectrodactyly–ectodermal dysplasia–cleft syndrome, EEC）是一类以缺指（趾）畸形、外胚层发育不良及口面裂为核心特征的常染色体显性遗传病。该疾病的核心表型及其他未被充分认知的附加表型均存在外显率降低的现象，这一点在产前病例中尤为突出。本文报道1例妊娠22周的EEC综合征胎儿，产前超声检查可见其唇腭裂及右侧多囊肾。通过全外显子组测序证实，该病例存在TP63基因R304W位点的新发错义突变，该突变与EEC综合征明确相关。我们进一步汇总了已报道的TP63相关产前病例，更完整地呈现了EEC综合征的产前表型谱。本研究揭示了TP63相关疾病中泌尿生殖系统异常的潜在严重性，并强调：当胎儿同时伴发口面裂或肢体畸形与泌尿生殖系统异常时，需针对EEC综合征的发病可能性向家属开展遗传咨询。