Juvenile polyposis syndrome (JPS) is a hereditary hamartomatous polyposis syndrome characterized by gastrointestinal juvenile polyps and increased risk of gastrointestinal cancer. Germline pathogenic variants are detected in SMAD4 or BMPR1A, however in a significant number of patients with JPS, the etiology is unknown. From Danish registers, and genetic department and laboratories, we identified all patients in Denmark with a clinical diagnosis of JPS and/or a pathogenic variant in BMPR1A or SMAD4. In patients where no variant had been detected, we performed genetic analysis, including whole genome sequencing. We collected clinical information on all patients to investigate the phenotypic spectrum. Sixty-six patients (mean age 40 years) were included of whom the pathogenic variant was unknown in seven patients. We detected a pathogenic variant in SMAD4 or PTEN in additional three patients and thus ≈ 95% of patients had a pathogenic germline variant. Endoscopic information was available in fifty-two patients (79%) and of these 31 (60%) fulfilled the clinical criteria of JPS. In 41 patients (79%), other types of polyps than juvenile had been removed. Our results suggest that almost all patients with a clinical diagnosis of JPS has a pathogenic variant in mainly BMPR1A, SMAD4, and more rarely PTEN. However, not all patients with a pathogenic variant fulfil the clinical criteria of JPS. We also demonstrated a wide clinical spectrum, and that the histopathology of removed polyps varied.

幼年性息肉病综合征（JPS）是一种遗传性错构瘤性息肉病综合征，其特征是胃肠道幼年性息肉和胃肠道癌症风险增加。SMAD4或BMPR1A中检测到种系致病变异，但在大量 JPS 患者中，其病因尚不清楚。从丹麦登记册、遗传部门和实验室，我们确定了丹麦所有临床诊断为 JPS 和/或BMPR1A或SMAD4致病性变异的患者。对于未检测到变异的患者，我们进行了遗传分析，包括全基因组测序。我们收集了所有患者的临床信息以调查表型谱。包括 66 名患者（平均年龄 40 岁），其中 7 名患者的致病变异未知。我们在另外三名患者中检测到SMAD4或PTEN 的致病性变异，因此约 95% 的患者具有致病性种系变异。52 名患者 (79%) 可获得内窥镜信息，其中 31 名患者 (60%) 符合 JPS 的临床标准。41 名患者 (79%) 中除幼年性息肉外其他类型的息肉已被切除。我们的结果表明，几乎所有临床诊断为 JPS 的患者都存在主要为BMPR1A、SMAD4以及较少见的PTEN的致病性变异。然而，并非所有携带致病性变异的患者都符合 JPS 的临床标准。我们还展示了广泛的临床谱，并且切除的息肉的组织病理学各不相同。