RARE DISEASE
Peutz-Jeghers syndrome
Peutz-Jeghers syndrome
Peutz-Jeghers syndrome
Synonyms: Hamartomatous intestinal polyposis, PJS
Synonyms: Hamartomatous intestinal polyposis, PJS
Synonyms: Hamartomatous intestinal polyposis, PJS
Drug discovery
0
drugs
With orphan designations
Overview
Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder caused by STK11 mutations, characterized by hamartomatous gastrointestinal polyps and mucocutaneous hyperpigmentation. Polyps cause complications like bowel obstruction and intussusception, often presenting in childhood. Patients face elevated cancer risks (gastrointestinal, pancreatic, breast, ovarian), with a cumulative lifetime cancer risk of up to 85% [1][2][15]. Diagnosis combines clinical findings, histopathology, and genetic testing [4][7].
Burden
Cancer: Cumulative risk of 57% by age 70 for GI cancers, 32–54% for breast cancer, and 11–36% for pancreatic cancer [15][2][7].
Morbidity: Recurrent bowel obstructions, anemia, and emergency surgeries in childhood [4][8][10].
Psychosocial impact: Chronic pain, anxiety from surveillance, and visible pigmentation [2][15].
Therapies
Surveillance: Endoscopic polypectomy (via double-balloon enteroscopy or intraoperative methods) to prevent obstruction [3][8][10]; cancer screening (e.g., colonoscopy, breast MRI, pancreatic imaging) starting in childhood/adolescence [7][11][15].
Surgery: Reserved for symptomatic polyps, intussusception, or malignancies [3][8][16].
Genetic counseling: Mandatory for families, with STK11 testing to guide surveillance [7][11].
Categories: rare developmental anomalies during embryogenesis, rare gastroenterological diseases, rare genetic diseases, rare neoplastic diseases, rare skin diseases, rare transplant-related disorders
Research Papers
381 drug discovery papers about Peutz-Jeghers syndrome, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
381 drug discovery papers about Peutz-Jeghers syndrome, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-06-30 | Pyloric botulinum toxin injection and single-port laparoscopic intragastric surgery for bulbus hamartoma.
Gastrointestinal polyps are associated with risks such as bleeding, intussusception, obstruction and malignancy, necessitating removal. Technological advancements in endoscopic and laparoscopic surgery have introduced minimally invasive options like laparoscopic intragastric surgery (LIGS), especially beneficial for polyps that cannot be resected endoscopically. This report presents a 37-year-old male patient with Peutz-Jeghers Syndrome who exhibited symptoms of nausea, vomiting and weight loss. Endoscopy and computed tomography imaging revealed obstructive polyps in the bulbus and gastric cardia. The patient underwent single-port LIGS with preoperative botulinum toxin injection to facilitate pyloric opening. This combined approach allowed effective lesion resection without requiring extensive gastric resection. Pathology confirmed a hamartomatous polyp in the bulbus and high-grade dysplasia with negative margin in the gastric cardia. LIGS, particularly with botulinum toxin assistance, appears to be a safe and effective method for excising intraluminal lesions in complex anatomical areas, such as the duodenal bulbus and cardia.
2026-06-22 | Distinct mucosa-associated microbiota signatures and dysbiosis in Peutz-Jeghers syndrome polyps versus paired normal mucosa
Background Peutz-Jeghers syndrome (PJS) is an STK11/LKB1 -mutated autosomal dominant disorder with gastrointestinal hamartomatous polyps and elevated cancer risk, but the role of mucosa-associated microbiota in PJS polyp pathogenesis remains unclear. Aim To investigate the mucosal microbial signatures, dysbiosis characteristics, and potential biomarkers in PJS polyps versus paired normal small intestinal mucosa. Methods A paired-sample design was adopted, enrolling 44 genetically confirmed PJS patients. Mucosa-associated microbiota was profiled via 5R 16S rRNA gene sequencing. Statistical analyses included Wilcoxon rank-sum test, ANOSIM, Spearman’s correlation, and random forest modeling. Results Alpha diversity (Observed species, Chao1, Shannon) was markedly reduced in polyps (all P < 0.001), while Simpson index increased (P < 0.001). Beta diversity differed significantly between groups (ANOSIM, R = 0.0667, P = 0.002). Polyps were enriched in Pseudomonadota (70.00% vs. 49.51%, P < 0.001) and depleted in Bacillota , Bacteroidota (both P < 0.001). Microbial dysbiosis index (MDI) was higher in polyps (P < 0.001). A 9-genera random forest model achieved AUC = 0.897. Escherichia-Shigella correlated with polyp number (P < 0.05), and Enterococcus correlated with CA72–4 levels (P < 0.05). Conclusion PJS polyps exhibit significant mucosal microbial dysbiosis, which may serve as potential biomarkers and therapeutic targets for PJS.
2026-05-25 | Adrenocortical Carcinoma in Peutz-Jeghers Syndrome With a Rare STK11 Pathogenic Germline Variant: A Case Report.
Peutz-Jeghers syndrome (PJS) is an inherited, autosomal-dominant condition, featuring STK11 germline mutations, characterized by hamartomatous gastrointestinal polyps and increased cancer risk. The most commonly associated malignancies are gastrointestinal, pancreatic, and breast cancers. Herein, we report an extremely rare case of PJS with adrenocortical carcinoma (ACC). A 40-year-old woman was referred to University of Tsukuba Hospital with uncontrolled diabetes mellitus (DM) and hypokalemia in July 2021. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a 12 cm mass in the right adrenal gland and aortocaval lymph node swelling. Mucocutaneous hyperpigmentation in her lips and fingertips was observed, and multiple stomach and small intestine polyps were visible on CT. We performed open right adrenalectomy with right nephrectomy, partial hepatectomy, and aortocaval lymph node dissection before diagnosing ACC with lymph node metastasis from the pathology. After surgery, multiple lung and liver metastases developed, and combination chemotherapy (etoposide, doxorubicin, and cisplatin, plus mitotane) was started, achieving stable disease for 2 years. We also performed an OncoGuide NCC Oncopanel on the adrenal tumor specimen and blood sample, revealing a rarely reported pathogenic germline variant (c.394T>C, p.C132R) in STK11. This variant was registered as Likely Pathogenic in the NIH Clinvar public database, which led to a PJS diagnosis. This is the second report of ACC associated PJS in a rare germline variant of STK11. Although rare, loss of STK11 function may lead to cancers outside expected sites in PJS cases.
2026-06-30 | Pyloric botulinum toxin injection and single-port laparoscopic intragastric surgery for bulbus hamartoma.
Gastrointestinal polyps are associated with risks such as bleeding, intussusception, obstruction and malignancy, necessitating removal. Technological advancements in endoscopic and laparoscopic surgery have introduced minimally invasive options like laparoscopic intragastric surgery (LIGS), especially beneficial for polyps that cannot be resected endoscopically. This report presents a 37-year-old male patient with Peutz-Jeghers Syndrome who exhibited symptoms of nausea, vomiting and weight loss. Endoscopy and computed tomography imaging revealed obstructive polyps in the bulbus and gastric cardia. The patient underwent single-port LIGS with preoperative botulinum toxin injection to facilitate pyloric opening. This combined approach allowed effective lesion resection without requiring extensive gastric resection. Pathology confirmed a hamartomatous polyp in the bulbus and high-grade dysplasia with negative margin in the gastric cardia. LIGS, particularly with botulinum toxin assistance, appears to be a safe and effective method for excising intraluminal lesions in complex anatomical areas, such as the duodenal bulbus and cardia.
2026-06-22 | Distinct mucosa-associated microbiota signatures and dysbiosis in Peutz-Jeghers syndrome polyps versus paired normal mucosa
Background Peutz-Jeghers syndrome (PJS) is an STK11/LKB1 -mutated autosomal dominant disorder with gastrointestinal hamartomatous polyps and elevated cancer risk, but the role of mucosa-associated microbiota in PJS polyp pathogenesis remains unclear. Aim To investigate the mucosal microbial signatures, dysbiosis characteristics, and potential biomarkers in PJS polyps versus paired normal small intestinal mucosa. Methods A paired-sample design was adopted, enrolling 44 genetically confirmed PJS patients. Mucosa-associated microbiota was profiled via 5R 16S rRNA gene sequencing. Statistical analyses included Wilcoxon rank-sum test, ANOSIM, Spearman’s correlation, and random forest modeling. Results Alpha diversity (Observed species, Chao1, Shannon) was markedly reduced in polyps (all P < 0.001), while Simpson index increased (P < 0.001). Beta diversity differed significantly between groups (ANOSIM, R = 0.0667, P = 0.002). Polyps were enriched in Pseudomonadota (70.00% vs. 49.51%, P < 0.001) and depleted in Bacillota , Bacteroidota (both P < 0.001). Microbial dysbiosis index (MDI) was higher in polyps (P < 0.001). A 9-genera random forest model achieved AUC = 0.897. Escherichia-Shigella correlated with polyp number (P < 0.05), and Enterococcus correlated with CA72–4 levels (P < 0.05). Conclusion PJS polyps exhibit significant mucosal microbial dysbiosis, which may serve as potential biomarkers and therapeutic targets for PJS.
2026-05-25 | Adrenocortical Carcinoma in Peutz-Jeghers Syndrome With a Rare STK11 Pathogenic Germline Variant: A Case Report.
Peutz-Jeghers syndrome (PJS) is an inherited, autosomal-dominant condition, featuring STK11 germline mutations, characterized by hamartomatous gastrointestinal polyps and increased cancer risk. The most commonly associated malignancies are gastrointestinal, pancreatic, and breast cancers. Herein, we report an extremely rare case of PJS with adrenocortical carcinoma (ACC). A 40-year-old woman was referred to University of Tsukuba Hospital with uncontrolled diabetes mellitus (DM) and hypokalemia in July 2021. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a 12 cm mass in the right adrenal gland and aortocaval lymph node swelling. Mucocutaneous hyperpigmentation in her lips and fingertips was observed, and multiple stomach and small intestine polyps were visible on CT. We performed open right adrenalectomy with right nephrectomy, partial hepatectomy, and aortocaval lymph node dissection before diagnosing ACC with lymph node metastasis from the pathology. After surgery, multiple lung and liver metastases developed, and combination chemotherapy (etoposide, doxorubicin, and cisplatin, plus mitotane) was started, achieving stable disease for 2 years. We also performed an OncoGuide NCC Oncopanel on the adrenal tumor specimen and blood sample, revealing a rarely reported pathogenic germline variant (c.394T>C, p.C132R) in STK11. This variant was registered as Likely Pathogenic in the NIH Clinvar public database, which led to a PJS diagnosis. This is the second report of ACC associated PJS in a rare germline variant of STK11. Although rare, loss of STK11 function may lead to cancers outside expected sites in PJS cases.
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