Department of Pediatrics, Kyushu Hospital, Japan Community Healthcare Organization, 1-8-1, Kishinoura, Yahatanishi-ku, Kitakyushu, Fukuoka, 806-8501, Japan.
Department of Child Health and Welfare (Pediatrics), Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan.
CEN Case Rep. 2023 May;12(2):184-188. doi: 10.1007/s13730-022-00742-x. Epub 2022 Oct 13.
Wilms tumor 1 (WT1) is the causative gene of Denys-Drash syndrome and Frasier syndrome, and in most cases, kidney failure develops after birth. We report an unusual case of Potter sequence due to fetal nephropathy and kidney failure with a WT1 mutation. The neonate was born at 37 weeks of gestation, and had no distinctive facial appearance or anomalies of the extremities. The external genitalia were ambiguous. Presence of a penile-like structure or hypertrophic clitoris was noted, and the urethra opened at the base of the penis or clitoris. On ultrasonographic examination, the kidney sizes were small. No kidney cysts were noted, but the kidney parenchymal luminosity was increased. Although the neonate received mechanical ventilation because of severe retractive breathing after birth, he died of poor oxygenation due to air leak syndrome at 60 h after birth. The congenital anomalies of the kidney and urinary tract (CAKUT) gene panel revealed a heterozygous missense mutation in WT1 [NM_024426.6:exon9:c.1400G > A, p.(Arg467Gln)]. In WT1, missense mutations are associated with earlier onset of nephropathy than nonsense or splicing mutations. However, severe cases of fetal onset and early neonatal death with WT1 mutations are rare, and only one severe case with the same missense mutation in WT1 has been reported. Therefore, WT1 mutation may be suspected in Potter sequence patients with external genital abnormalities, and the WT1 missense mutation in our case [NM_024426.6:exon9:c.1400G > A, p.(Arg467Gln)] may indicate a severe case with fetal onset of nephropathy and kidney failure.
Wilms 瘤 1(WT1)是 Denys-Drash 综合征和 Frasier 综合征的致病基因,大多数情况下,出生后会发生肾衰竭。我们报告了一例由于胎儿肾病和 WT1 突变引起的 Potter 序列不常见病例。新生儿在 37 周妊娠时出生,无明显面部特征或四肢异常。外生殖器模糊。注意到有阴茎样结构或肥大的阴蒂,尿道开口于阴茎或阴蒂的基部。超声检查显示肾脏较小。未发现肾囊肿,但肾实质亮度增加。尽管新生儿在出生后因严重的回缩性呼吸而接受机械通气,但由于气胸综合征,他在出生后 60 小时因缺氧而死亡。先天性肾和尿路异常(CAKUT)基因谱显示 WT1 中的杂合错义突变[NM_024426.6:exon9:c.1400G > A,p.(Arg467Gln)]。在 WT1 中,错义突变与肾病的发病更早相关,而无义或剪接突变则与发病较晚相关。然而,WT1 突变的胎儿起病和早发性新生儿死亡的严重病例很少见,并且仅报告了一例具有相同 WT1 错义突变的严重病例。因此,WT1 突变可能怀疑有外生殖器异常的 Potter 序列患者,而我们病例中的 WT1 错义突变[NM_024426.6:exon9:c.1400G > A,p.(Arg467Gln)]可能表明胎儿起病的严重肾病和肾衰竭。