Analysis of familial steroid-sensitive nephrotic syndrome

激素敏感型特发性肾病综合征(SSN)是儿童最常见的肾病综合征。在大多数情况下，SSN是零星发生的，被认为是一种多因素疾病。但有时也可观察到家族聚集性SSN。为了更好地确定遗传因素的贡献，我们对14个日本血统的无血缘关系的SSN家族的临床特征和遗传影响进行了回顾性研究。平均发病年龄4.3岁。患病同胞之间的发病间隔为2.9岁，与欧洲SSN家系队列特征十分相似。尽管在发病年龄方面有相当大的家庭内一致性，但治疗反应和随后的复发频率在特定家庭中受影响的同胞之间，甚至在受影响的同卵双胞胎之间也存在某种程度的差异。大多数患者在最初的治疗后经历了几次非频繁的复发，并进入完全的持续缓解，直到15岁。8名患者的临床病程更长，因为他们变得频繁复发和类固醇依赖。8例肾活检显示肾小球轻度异常。一半的患者(46%)有过敏性疾病。28例患者在观察期内均保持正常肾功能。我们的结果表明，这个队列代表了SSN的一种家族性形式，模仿了常见的散发性SSN，并将构成微小病变型肾病综合征的一个亚群，其中隐性遗传因素在发病机制中发挥着重要作用，可能与某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.