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Abstract：
Sotos syndrome is an autosomal dominant condition characterized by overgrowth with advanced bone age, macrodolicocephaly, motor developmental delays and learning difficulties, and characteristic facial features caused by heterozygous pathogenetic variants in the NSD1 gene located on chromosome 5q35. The prevalence of heart defects (HDs) in individuals with Sotos syndrome is estimated to be around 15-40%. Septal defects and patent ductus arteriosus are the most commonly diagnosed malformations, but complex defects have also been reported. The aim of our study was to analyze the prevalence of HD, the anatomic types, and the genetic characteristics of 45 patients with Sotos syndrome carrying pathogenetic variants of NSD1 or a 5q35 deletion encompassing NSD1, who were followed at Bambino Gesù Children\'s Hospital in Rome. Thirty-nine of the forty-five patients (86.7%) had a mutation in NSD1, while six of the forty-five (13.3%) had a deletion. Most of the patients (62.2%, 28/45) were male, with a mean age of 14 ± 7 years (range 0.2-37 years). A total of 27/45 (60.0%) of the patients had heart defects, isolated or combined with other defects, including septal defects (12 patients), aortic anomalies (9 patients), mitral valve and/or tricuspid valve dysplasia/insufficiency (1 patient), patent ductus arteriosus (3 patients), left ventricular non-compaction/hypertrabeculated left ventricle (LV) (4 patients), aortic coarctation (1 patient), aortopulmonary window (1 patient), and pulmonary valve anomalies (3 patients). The prevalences of HD in the two subgroups (deletion versus intragenic mutation) were similar (66.7% (4/6) in the deletion group versus 58.91% (23/39) in the intragenic variant group). Our results showed a higher prevalence of HD in patients with Sotos syndrome in comparison to that described in the literature, with similar distributions of patients with mutated and deleted genes. An accurate and detailed echocardiogram should be performed in patients with Sotos syndrome at diagnosis, and a specific cardiological follow-up program is needed.
摘要：
Sotos综合征是一种常染色体显性遗传病，其特征是骨龄过度生长，大头畸形，运动发育迟缓和学习困难，以及由位于染色体5q35上的NSD1基因的杂合致病变异引起的特征性面部特征。据估计，Sotos综合征患者的心脏缺陷（HD）患病率约为15-40％。房间隔缺损和动脉导管未闭是最常见的诊断畸形，但复杂的缺陷也有报道。我们研究的目的是分析HD的患病率，解剖类型，以及45例携带NSD1致病变异或包含NSD1的5q35缺失的Sotos综合征患者的遗传特征，这些患者在罗马的BambinoGes图儿童医院接受随访。45例患者中有39例（86.7％）具有NSD1突变，而45例患者中有6例（13.3％）具有缺失。大多数患者（62.2%，28/45）是男性，平均年龄14±7岁（范围0.2-37岁）。共有27/45(60.0%)的患者有心脏缺陷,孤立或与其他缺陷结合，包括间隔缺损（12例），主动脉异常（9例），二尖瓣和/或三尖瓣发育不良/功能不全（1例），动脉导管未闭（3例），左心室致密化不全/左心室过度扩张（LV）（4例），主动脉缩窄（1例），主肺动脉窗（1例），和肺动脉瓣异常（3例）。两个亚组（缺失与基因内突变）中HD的患病率相似（缺失组为66.7％（4/6），基因内变异组为58.91％（23/39））。我们的结果显示，与文献中描述的相比，Sotos综合征患者的HD患病率更高。突变和缺失基因的患者分布相似。诊断时应该对Sotos综合征患者进行准确详细的超声心动图检查，需要特定的心脏病随访计划。
