Analysis of familial steroid-sensitive nephrotic syndrome

类固醇敏感性特发性肾病综合征（SSN）是儿童中最常见的肾病综合征。在大多数情况下，SSN零星发生，被认为是一种多因素疾病。然而，有时会观察到家族聚集性SSN。为了更好地确定遗传因素的作用，我们回顾性研究了14个非近亲、无血缘关系的日本裔SSN家族的临床特征和遗传影响。平均发病年龄为4.3岁。患病兄弟姐妹之间的发病间隔为2.9岁，这与欧洲SSN家庭队列的特征非常相似。尽管在发病年龄方面有相当大的家族内一致性，但治疗反应性和随后的复发频率在特定家庭中受影响的兄弟姐妹之间，甚至在受影响的同卵双胞胎之间也有所不同。大多数患者在初始治疗后经历了几次不频繁的复发，并进入了一个完全持续的缓解期，直到15岁。8名患者由于频繁复发和类固醇依赖而延长了临床病程。肾活检显示8例患者肾小球轻微异常。一半的患者（46%）患有过敏性疾病。28例患者在观察期内肾功能均保持正常。我们的研究结果表明，该队列代表了一种家族性的SSN，模仿了一种常见的散发性对偶，并将构成微小变化肾病综合征的一个亚群，其中隐性遗传因素在发病机制中起重要作用，可能与一些表观遗传或环境因素相互作用。

Steroid sensitive idiopathic nephrotic syndrome (SSN) is the most common nephrotic syndrome in children. In most cases, SSN occurs sporadically and is considered to be a multifactorial disorder. However, familial clustering SSN was sometimes observed. To better define the contribution of genetic factors, we retrospectively studied clinical features and genetic influences in a cohort of 14 non consanguineous, unrelated SSN families of Japanese origin. The average age of onset was 4.3 years old. The interval of the onset between the affected sib-pair was 2.9 years old, which are quite similar to the features of European SSN families cohort. Despite the considerable intra-familial concordance with respect to the age of onset, therapeutic responsiveness and subsequent relapse frequency varied somehow between the affected sibs within a given family, even between affected monozygotic twins. Most patients experienced several, non-frequent relapses after initial treatment and enterd a complete sustained remission until age of 15 years. Eight patients had a more prolonged clinical course as they became frequent-relapsers and steroid-dependent. Renal biopsy showed minor glomerular abnormalities in 8 patients. A half of the patients (46%) had allergic diseases. All the 28 patients maintained a normal renal function during the observation period. Our results indicate that this cohort represents a familial form of SSN mimicking a common sporadic counterpart and will constitutes a subgroup of minimal change nephrotic syndrome where the recessive genetic factors plays a substantial role in the pathogenesis, possibly interacting with some epigenetic or environmental factors.