Inoki Yuta, Horinouchi Tomoko, Aoyama Shuhei, Kimura Yuka, Ichikawa Yuta, Tanaka Yu, Ueda Chika, Kitakado Hideaki, Kondo Atsushi, Sakakibara Nana, Kamei Koichi, Hamada Riku, Fujita Naoya, Gotoh Yoshimitsu, Kaku Yoshitsugu, Nishiyama Kei, Okamoto Takayuki, Toya Yukiko, Yamamura Tomohiko, Ishimori Shingo, Nagano China, Nozu Kandai
Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-Cho, Chuo, Kobe, Hyogo, 650-0017, Japan.
Division of Nephrology and Rheumatology, National Center for Child Health and Development, Setagaya-Ku, Tokyo, Japan.
Pediatr Nephrol. 2025 Mar 17. doi: 10.1007/s00467-025-06735-z.
More than half of patients with congenital nephrotic syndrome (CNS) or infantile nephrotic syndrome (infantile NS) have a monogenic aetiology. This study aimed to clarify differences in the clinical course, genetic background, and genotype-phenotype correlation between CNS and infantile NS.
We enrolled patients who were diagnosed with CNS or infantile NS and referred to our hospital for genetic analysis and investigated the clinical characteristics and genetic background of patients with identified causative genes.
Among 74 patients enrolled, disease-causing genetic variants were detected in 50 patients. The median age for developing kidney failure in the genetic CNS (n = 33) and genetic infantile NS (n = 17) groups with monogenic variants was 13.2 and 19.0 months, respectively (P = 0.13). The age at developing kidney failure was significantly earlier in CNS patients with genes other than NPHS1 than in CNS patients with NPHS1 variants (1.0 vs. 31.0 months; P < 0.001). In patients with pathogenic variants other than NPHS1, there was a significant difference in the age at developing kidney failure between CNS and infantile NS patients (1.0 vs. 15.0 months; P < 0.001). Of patients with NPHS1 variants, no infants with NS had any truncating variants or developed kidney failure during follow-up.
The onset of CNS or infantile NS affects the kidney prognosis in patients with genetic nephrotic syndrome. Among patients with pathogenic variants in the same gene, patients with infantile NS may have a milder genotype and better prognosis than those with CNS.
超过半数的先天性肾病综合征（CNS）或婴儿肾病综合征（婴儿型NS）患者有单基因病因。本研究旨在阐明CNS与婴儿型NS在临床病程、遗传背景及基因型-表型相关性方面的差异。
我们纳入了被诊断诊断为CNS或婴儿型NS诊断并转诊至我院进行基因分析的患者，并调查了已鉴定致病基因患者的临床特征和遗传背景。
在纳入的74例患者中，50例检测到致病基因变异。具有单基因变异的遗传性CNS组（n = 33）和遗传性婴儿型NS组（n = 17）发生肾衰竭的中位年龄分别为13.2个月和19.0个月（P = 0.13）。NPHS1基因以外的基因导致的CNS患者发生肾衰竭的年龄显著早于NPHS1变异的CNS患者（1.0个月对31.0个月；P < 0.001）。在NPHS1以外的致病变异患者中，CNS和婴儿型NS患者发生肾衰竭的年龄存在显著差异（1.0个月对15.0个月；P < 0.001）。在NPHS1变异患者中，婴儿型NS患者在随访期间均无截短变异或发生肾衰竭。
CNS或婴儿型NS的发病影响遗传性肾病综合征患者的肾脏预后。在同一基因致病变异的患者中，婴儿型NS患者的基因型可能比CNS患者更轻，预后更好。
