Eye involvement in children with primary focal segmental glomerulosclerosis

Distinct eye abnormalities have been described in children with nephrotic syndrome, particularly in diffuse mesangial sclerosis (i.e. Pierson syndrome). The aim of the study was to investigate whether there were any associated ocular anomalies in children with steroid-resistant nephrotic syndrome (SRNS), all of whom had revealed primary focal segmental glomerulosclerosis in biopsy. Thirty-three SRNS patients (16 male, 17 female) with a median age of 10.5 years (range 3–25 years) were enrolled in the study. Twenty steroid-sensitive nephrotic syndrome (SSNS) patients (ten male, ten female) with a median age of 8 years (range 3–15 years) served as controls. All SRNS patients were examined by mutational analysis for mutations in the NPHS2, WT1, and LAMB2 genes. Nine out of 33 SRNS patients (27.2%) showed various eye abnormalities. However, no abnormal ocular findings were detected in any of the SSNS patients. Abnormal eye findings detected in SRNS patients were anisometropic amblyopia (n = 4), Mittendorf’s dots (n = 4), myopic astigmatism (n = 3) and exotropia (n = 1). Macular pigment changes (n = 1), posterior subcapsular opacities (n = 1) and cataract (n = 1) were considered as steroid-induced side effects. In four patients, more than one eye abnormality was found. Mutational analysis for the NPHS2, WT1 and LAMB2 genes revealed disease-causing mutations in 24.2% of patients. Homozygous NPHS2 mutations were detected in five patients (15.1%), all of whom had parental consanguinity. In three patients (9%) from non-consanguineous parents, heterozygous de novo WT1 mutations were detected as disease-causing mutations. No LAMB2 mutation was detected in any patient. While four out of five (80%) patients with homozygous NPHS2 mutations showed at least one abnormal ocular finding (i.e. Mittendorf’s dot or anisometric amblyopia), none of the patients with a WT1 mutation had ocular involvement. In conclusion, ocular involvement may accompany SRNS caused by primary focal segmental glomerulosclerosis (FSGS). Ophthalmologic evaluation at the time of diagnosis might be beneficial to characterize further the spectrum of this possible association.