A case of Potter sequence with WT1 mutation

Abstract

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.

Keywords: External genital abnormality; Kidney failure; Missense mutation; Potter sequence; Wilms tumor 1.

Fig. 1

Fetal MRI at 33 weeks of gestation. a Pulmonary hypoplasia was observed. b Kidney size was at the upper limit of normal and no kidney cysts were noted

Fig. 2

Ambiguous external genitalia. Penile-like structure or hypertrophic clitoris, urethra opening at the base of the penis or clitoris, dysplasia of the scrotum or labia, and non-palpable testis were noted

Fig. 3

Kidney ultrasonography. Right and left kidney lengths were 30 mm and 38 mm, respectively, and no kidney cysts were noted. Kidney parenchymal luminosity was increased

Fig. 4

Clinical course after birth. sBP systolic blood pressure, dBP diastolic blood pressure, Alb albumin, mPSL methylprednisolone

Fig. 5

Next-generation sequencing of the CAKUT gene panel (181 genes)