Alarcón Ignacio, Peralta Carolina, Cammarata-Scalisi Francisco, Araya Castillo Maykol, Cano Francisco, Rojo Angélica, Ceballos María Luisa, Krall Paola
Escuela de Medicina, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Servicio de Pediatría, Hospital de Antofagasta, Antofagasta, Chile.
Front Nephrol. 2025 Jan 31;4:1375538. doi: 10.3389/fneph.2024.1375538. eCollection 2024.
Steroid-resistant nephrotic syndrome (SRNS) is a rare kidney disease commonly characterized histopathologically by focal and segmental glomerulosclerosis (FSGS) or minimal change disease. One-third of SRNS-FSGS cases are attributed to a genetic cause ultimately leading to end-stage kidney disease (ESKD) during childhood or adulthood. variants, although rare, typically manifest in early adulthood as SRNS-FSGS with autosomal dominant inheritance pattern and are associated with variable progression toward ESKD.
CASE–DIAGNOSIS/TREATMENT: A 10-year-old Chilean male patient, born to a complicated pregnancy without any history of prenatal care, was incidentally found to have mild proteinuria during pre-surgery analysis. He was diagnosed with nephrotic syndrome and treatment with prednisone was started, but 12 months later, he persisted with hyperlipidemia, hypoalbuminemia, and proteinuria. Within a few weeks, proteinuria rapidly increased, and a kidney biopsy exhibited FSGS features. At the age of 12, he reached ESKD and initiated peritoneal dialysis, experiencing an episode of posterior reversible encephalopathy syndrome. Exome sequencing identified a novel variant of uncertain significance (VUS), c.625_633del that predicted the in-frame deletion p.L209_E211del in a highly conserved functional domain. He requested to be considered for kidney transplantation and the VUS in was re-analyzed to assess potential risks, resulting in a reclassification as likely pathogenic (PM1+PM2+PM4 criteria). At 14 years old, he received a deceased donor kidney allograft without recurrence during the subsequent 5 months.
Identifying VUS is a recurring challenge in routine clinical genetics, particularly for patients with rare diseases or atypical phenotypes in underrepresented populations. This case underscores the benefit of timely genetic diagnosis taking into account the patient's request. VUS reassessment becomes more relevant when considering a kidney transplant not only as an appropriate procedure, but as the therapy of choice, especially considering the patient's history of complications with variable long-term consequences.
激素抵抗型肾病综合征（SRNS）是一种罕见的肾脏疾病，其组织病理学特征通常为局灶节段性肾小球硬化（FSGS）或微小病变病。三分之一的SRNS-FSGS病例归因于遗传原因，最终导致儿童期或成年期的终末期肾病（ESKD）。 变异虽然罕见，但通常在成年早期表现为具有常染色体显性遗传模式的SRNS-FSGS，并与向ESKD的可变进展相关。
病例诊断/治疗：一名10岁智利男性患者，出生于复杂妊娠且无任何产前护理史，在术前分析中偶然发现轻度蛋白尿。他被诊断为肾病综合征并开始用泼尼松治疗，但12个月后，他仍有高脂血症、低蛋白血症和蛋白尿。几周内，蛋白尿迅速增加，肾脏活检显示FSGS特征。12岁时，他发展为ESKD并开始腹膜透析，经历了一次后部可逆性脑病综合征发作。外显子组测序鉴定出一个意义未明的新变异（VUS），即c.625_633del，该变异预测在一个高度保守的功能域中发生框内缺失p.L209_E211del。他请求考虑进行肾移植，并对 中的VUS进行重新分析以评估潜在风险，结果重新分类为可能致病（PM1+PM2+PM4标准）。14岁时，他接受了 deceased donor 肾脏移植，随后5个月内未复发。
识别VUS是常规临床遗传学中反复出现的挑战，特别是对于在代表性不足人群中患有罕见疾病或非典型表型的患者。该病例强调了考虑患者请求进行及时基因诊断的益处。当考虑将肾移植不仅作为一种合适的手术，而且作为首选治疗方法时，VUS重新评估变得更加重要，尤其是考虑到患者具有可变长期后果的并发症病史。
