We present the case of a patient with a WT1 exon 10 variant whose clinical features resemble those of DDS. EH was also observed, a pathological finding related to WT1 variants.
The most common histopathology in WT1 disease is FSGS; however, diffuse mesangial sclerosis (DMS) is considered specific for WT1 disease. DMS is more common in children diagnosed before 2 years of age than in older children and is almost exclusively associated with exonic missense variants.
A woman from a family with a WT1 exon 10 missense variant was reported to have developed a Wilms tumor at 9 years of age, followed by slowly progressive nephropathy. The histopathological findings of the remaining kidney showed nephropathy (details are unknown) and hypertrophy. The younger brother with the same variant had normal renal function, and the mother showed slowly progressive nephropathy in adulthood, with histopathology in the early stages showing minimal change in nephropathy [2]. In Japan, a girl with a nonsense variant of WT1 exon 10 had her first abnormal urinalysis result at 9 years of age, subsequently developed slowly progressive nephropathy, and underwent a kidney transplant at 15 years of age (unpublished). Histopathological examination of the kidney revealed FSGS. All previously reported cases of WT1 exon 10 variants showed slowly progressive nephropathy, but some older children developed Wilms tumors, suggesting that the risk of tumor development should be considered in the treatment of patients with these variants.
Histopathological findings in the initial renal biopsy specimen in this case were consistent with those of FSGS-NOS. Since pathological variants in exon 10 of WT1 have rarely been reported, we have not been able to prove whether this variant is pathogenic. Based on the age of onset of the child, the rapid progression of nephropathy and external genitalia abnormalities, his clinical features resembled DDS, making pathologic variants very likely, but the histopathology was not consistent with typical DDS. Furthermore, the patient had a chromosomal abnormality that could have been responsible for his psychomotor retardation and external genitourinary abnormalities. FSGS is one of the glomerular lesions that occurs in the context of 21 trisomy, but the association is unknown because it has only been reported in case reports.
The EH observed in the kidney pathology in this case was the EH of Boman’s capsular epithelium (EHBCE), defined as the aggregation of small, uniform juvenile cells around the glomerulus [3]. EHBCE is commonly observed in the kidneys of pediatric patients on dialysis, and this case is no exception. However, Fukuzawa et al. [4]. found EHBCE in the renal tissue of a patient with a variant WT1 and described the possibility that the variant WT1 and the expression of PAX2 in podocytes are involved in the development of EHBCE. Furthermore, metanephric adenoma, which has been reported to be associated with EHBCE, has a phenotypic correlation with limbal NR in immunohistochemistry, and both are derived from cells with arrested differentiation in the sigmoid duct [5]. The patient had been on dialysis for less than a year and it is possible that the WT1 variant was associated with the development of EHBCE; however, no immunostaining was performed to confirm this.
This patient had a variant of WT1 exon 10 missense and a clinical course similar to that of DDS, although the histopathological findings of the initial renal biopsy showed FSGS. It would be desirable to elucidate the pathogenicity of WT1 variants and accumulate more cases that demonstrate an association between WT1 variants and EHBCE.