PJS affects males and females equally across all ethnic groups. It is estimated to occur in 1 in 25,000 to 1 in 300,000 births worldwide. Approximately 45% of cases arise from new mutations with no prior family history.

PJS is caused by mutations in the STK11 (also known as LKB1) gene, located at chromosome 19p13.3 (see RareShare guide on chromosomal nomenclature). The gene normally functions as a tumor suppressor, regulating cell growth, polarity and metabolism. The condition can follow an autosomal dominant pattern of inheritance (see RareShare guide on genetic inheritance), where inheritance of the mutated gene from one parent is sufficient to cause the syndrome. However, in about 45% of cases, the mutation arises from a new mutation with no family history.

Symptoms typically begin in childhood or early adolescence and include:

• Mucocutaneous Pigmentation: Dark blue, brown, or black macules (freckles) around the lips, inside the mouth (oral mucosa), and on the fingers, toes, and around the eyes and nose. These often appear in childhood and may fade as the person ages.

• Gastrointestinal Polyps: The development of hamartomatous (non-cancerous growth composed of a mixture of abnormal and normal cells) polyps, most commonly in the small intestine, but also in the stomach and large intestine.

• Abdominal Pain: Often caused by large polyps pulling on the bowel, leading to intussusception (when one part of the intestine slides into another like a telescope).

• GI Bleeding: Polyps can bleed, leading to blood in the stool or chronic iron-deficiency anemia (fatigue, weakness).

• Bowel Obstruction: Blockages caused by the size or accumulation of polyps.

Cancer-related manifestations in later life: Increased risk of colorectal, pancreatic, gastric, breast, ovarian/uterine and testicular tumors.

A clinical diagnosis of PJS is typically made if a patient meets certain criteria, such as having two or more Peutz-Jeghers-type polyps, characteristic pigmentation, or a family history of the syndrome. Diagnostic tools include:

• Genetic Testing: A blood or saliva test to identify a mutation in the STK11 gene confirms the diagnosis.

• Endoscopy and Colonoscopy: To visualize and remove polyps in the upper and lower GI tract.

• Capsule Endoscopy or MRI Enterography: Used specifically to examine the small intestine where standard endoscopes cannot reach.

Histology (microscopic examination of tissue samples): Hamartomatous polyps with a branching smooth muscle core.

There is currently no cure for PJS. Treatment focuses on managing symptoms and proactive surveillance to detect polyps or cancers early:

• Polypectomy: Removal of GI polyps during endoscopic procedures to prevent bleeding, obstruction, or malignant transformation.

• Surgery: Surgical intervention may be required if a polyp causes a bowel obstruction or intussusception, or if a polyp cannot be safely removed via endoscopy.

• Aggressive Cancer Surveillance: Routine, lifelong screening is the cornerstone of PJS management. This includes frequent colonoscopies, upper endoscopies, capsule endoscopies, breast MRIs/mammograms, pancreatic screening (endoscopic ultrasound or MRI), and gynecological exams.

Supportive care: Pain management, iron supplements to manage anemia from chronic GI bleeding, and genetic counseling.

With rigorous medical surveillance and endoscopic management, most individuals with PJS can achieve a good quality of life and life expectancy. However, lifetime risk of cancer is substantially elevated (>80%). The median age at first cancer diagnosis in PJS is 42-26 years. GI complications can be a major cause of morbidity, particularly in childhood and early adulthood.

1. Sandru F, Petca A, Dumitrascu MC, Petca RC, Carsote M. “Peutz-Jeghers syndrome: Skin manifestations and endocrine anomalies (Review).” 2021. Exp Ther Med. 22(6):1387. doi: 10.3892/etm.2021.10823. Epub 2021 Sep 29. PMID: 34650635; PMCID: PMC8506952.

2. Yamamoto H, Sakamoto H, Kumagai H, Abe T, Ishiguro S, Uchida K, Kawasaki Y, Saida Y, Sano Y, Takeuchi Y, Tajika M, Nakajima T, Banno K, Funasaka Y, Hori S, Yamaguchi T, Yoshida T, Ishikawa H, Iwama T, Okazaki Y, Saito Y, Matsuura N, Mutoh M, Tomita N, Akiyama T, Yamamoto T, Ishida H, Nakayama Y. 2023. “Clinical Guidelines for Diagnosis and Management of Peutz-Jeghers Syndrome in Children and Adults.” Digestion.104(5):335-347. doi: 10.1159/000529799. Epub 2023 Apr 13. PMID: 37054692.

3. National Organization for Rare Disorders (NORD):  Peutz-Jeghers syndrome.

4. Orphanet:  Peutz-Jeghers syndrome.