Koga Nobuhiko, Yatsuga Shuichi, Kubota Kei, Niimi Toshikazu, Inoue Takahito, Nagamitsu Shinichiro
Department of Pediatrics, Fukuoka University School of Medicine, 7-45-1, Nanakuma, Jonan-Ku, Fukuoka City, Fukuoka, 814-0180, Japan.
J Med Case Rep. 2025 Jun 13;19(1):273. doi: 10.1186/s13256-025-05344-6.
Noonan syndrome has a wide range of symptoms due to dysregulation of the RAS/MAPK pathway with several gene variations, including the PTPN11 gene. There are currently no case reports of Noonan syndrome with eosinophilic gastroenteritis.
A 14-year-old Japanese girl was clinically diagnosed with Noonan syndrome. She had intermittent abdominal pain and vomiting from 10 years old. The patient was diagnosed with eosinophilic gastroenteritis on the basis of the pathological finding of multiple foci with > 20 eosinophils/high power field in the mucosal lamina propria of the colon by endoscopy at 12 years old. Vomiting and abdominal pain are currently being controlled by antihistamines and leukotriene antagonist therapy. Genetic testing showed the missense variation p.Ala72Gly in the PTPN11 gene.
The pathogenesis of eosinophilic gastroenteritis is similar to that of other allergic inflammatory diseases, such as bronchial asthma. The cause of eosinophilic gastroenteritis is multifactorial, including genetic and environmental factors. The PTPN11 gene variations are suggested to promote eosinophilic disorders by leading to the activation of the RAS/MAPK pathway. This activation subsequently results in the production of interleukin-5, which plays a crucial role in the pathogenesis of eosinophilic gastroenteritis. The relationship between eosinophilic gastroenteritis and the PTPN11 gene has not yet been reported.
We herein present the first known case of eosinophilic gastroenteritis in Noonan syndrome with a variation in the PTPN11 gene. The relationship between Noonan syndrome and eosinophilic gastroenteritis remains unknown; therefore, additional case reports of Noonan syndrome with eosinophilic gastroenteritis are required to elucidate this potential relationship.
努南综合征由于RAS/MAPK信号通路失调以及包括PTPN11基因在内的多种基因变异，具有广泛的症状。目前尚无努南综合征合并嗜酸性粒细胞性胃肠炎的病例报告。
一名14岁日本女孩临床诊断为努南综合征。她从10岁起就有间歇性腹痛和呕吐症状。该患者在12岁时接受内镜检查，根据结肠黏膜固有层多个病灶每高倍视野嗜酸性粒细胞>20个的病理结果，被诊断为嗜酸性粒细胞性胃肠炎。目前呕吐和腹痛通过抗组胺药和白三烯拮抗剂治疗得到控制。基因检测显示PTPN11基因存在错义变异p.Ala72Gly。
嗜酸性粒细胞性胃肠炎的发病机制与其他过敏性炎症性疾病如支气管哮喘相似。嗜酸性粒细胞性胃肠炎的病因是多因素的，包括遗传和环境因素。PTPN11基因变异被认为通过导致RAS/MAPK信号通路激活来促进嗜酸性粒细胞疾病。这种激活随后导致白细胞介素-5的产生，白细胞介素-5在嗜酸性粒细胞性胃肠炎的发病机制中起关键作用。嗜酸性粒细胞性胃肠炎与PTPN11基因之间的关系尚未见报道。
我们在此报告首例已知的努南综合征合并嗜酸性粒细胞性胃肠炎且伴有PTPN11基因变异的病例。努南综合征与嗜酸性粒细胞性胃肠炎之间的关系仍不清楚；因此，需要更多努南综合征合并嗜酸性粒细胞性胃肠炎的病例报告来阐明这种潜在关系。
