Peutz Jeghers Syndrome: Symptoms, Types, Causes and Treatment

Peutz-Jeghers Syndrome (PJS) is a rare, inherited condition with distinctive features that profoundly impact the lives of affected individuals and their families. Known for its striking mucocutaneous pigmentation and the development of multiple gastrointestinal polyps, PJS poses unique clinical challenges, including significant cancer risks and potentially life-threatening complications. This article explores the syndrome’s symptoms, types, causes, and modern treatment approaches, drawing from current research and clinical guidelines to provide a clear, human-centered overview.

Symptoms of Peutz Jeghers Syndrome

Peutz-Jeghers Syndrome reveals itself through a combination of visible and internal symptoms. Many of these signs start early in life, sometimes even in childhood, and can be clues for early diagnosis—crucial for reducing complications and cancer risk.

Feature	Description	Typical Onset	Source(s)
Pigmentation	Dark spots on lips, mouth, fingers, perianal, etc.	Childhood	1, 2, 5, 11
GI Polyps	Multiple hamartomatous polyps in GI tract	Childhood-Teens	1, 3, 5, 11
Abdominal Pain	Recurrent, linked to polyps/intussusception	Childhood-Adult	1, 3, 4, 5
Bleeding	GI bleeding, anemia	Any age	1, 5, 11, 14
Obstruction	Bowel obstruction, intussusception	Often young age	3, 4, 5, 10
Cancer Risk	Increased GI and non-GI malignancy risk	Adulthood	2, 8, 11, 12

Table 1: Key Symptoms

Mucocutaneous Pigmentation

One of the earliest and most recognizable symptoms is the appearance of small, dark-colored spots—known as lentigines—on the lips, inside and around the mouth, fingers, toes, and sometimes around the eyes, nostrils, and anus. These spots often develop in early childhood and can fade with age, but are an important diagnostic clue. Less commonly, similar spots are seen on the hands and feet. The severity of pigmentation often correlates with the number and size of gastrointestinal polyps 1, 2, 5, 11.

Gastrointestinal Polyps

PJS is marked by multiple benign (hamartomatous) polyps that can occur anywhere in the gastrointestinal tract, but are most commonly found in the small intestine, followed by the colon and stomach. These polyps can cause a range of symptoms from abdominal pain and chronic bleeding to more severe issues like bowel obstruction and intussusception (where one part of the intestine slides into another) 1, 3, 4, 5, 11.

Abdominal Symptoms

• Pain: Recurrent abdominal pain is common and may be due to polyp growth, intussusception, or bowel obstruction.
• GI Bleeding & Anemia: Polyps can bleed, sometimes causing chronic blood loss and resulting in anemia.
• Obstruction & Intussusception: Large or multiple polyps can lead to bowel obstruction or intussusception, which may require emergency intervention 3, 4, 5, 10, 14.

Cancer Risk

Perhaps the most serious long-term symptom is an increased risk for several cancers, both in the GI tract (such as small bowel, colon, stomach, and pancreas) and outside it (including breast, ovarian, cervical, testicular, and lung cancer). This risk rises with age and underscores the importance of regular surveillance 2, 8, 11, 12.

Types of Peutz Jeghers Syndrome

While Peutz-Jeghers Syndrome is generally considered a single genetic disorder, its manifestations vary widely. These variations can be grouped based on clinical presentation, genetic findings, and associated tumor types.

Type/Manifestation	Defining Features	Prevalence/Pattern	Source(s)
Classic PJS	Pigmentation + GI hamartomatous polyps	Most common	2, 5, 11
Non-classic/Attenuated	Milder pigment, fewer/smaller polyps	Less common	9
Ovarian Tumor Association	Sex-cord tumors with annular tubules (SCTATs)	Females, ~1/3 with SCTATs	2, 6
Testicular Tumor Assoc.	Large cell calcifying Sertoli cell tumors (LCCSCTs)	Males, rare	2
Cancer-predominant	Marked by early/multiple cancers	Variable, higher in females	2, 8

Table 2: Clinical Types and Associations

Classic Peutz-Jeghers Syndrome

The majority of PJS cases fit the classic profile: prominent mucocutaneous pigmentation and multiple GI hamartomatous polyps. This group carries the hallmark risks for polyp complications and malignancies 2, 5, 11.

Non-classic or Attenuated Forms

Some patients, especially those with certain STK11 gene mutations, may exhibit milder symptoms: less obvious pigmentation and fewer or smaller polyps. These individuals often present later or may be diagnosed after a family member is identified 9.

Tumor-Associated Subtypes

• Females: There is a well-established association with ovarian sex-cord tumors, particularly sex-cord tumors with annular tubules (SCTATs). Up to one-third of women with PJS may develop these tumors, which can be benign or, rarely, malignant. Additionally, PJS increases the risk of gynecological cancers, including cervical and uterine cancer 2, 6.
• Males: Boys and young men with PJS may develop testicular tumors, primarily large cell calcifying Sertoli cell tumors (LCCSCTs), which can lead to early puberty and are usually benign 2.

Cancer-Predominant Presentations

Some PJS families or individuals have a high burden of cancer, either because of genetic factors or the presence of certain mutations (e.g., "null" mutations in STK11). These cases often require more intensive surveillance 2, 8.

Causes of Peutz Jeghers Syndrome

Understanding the cause of Peutz-Jeghers Syndrome is crucial for effective diagnosis, family counseling, and targeted therapies. At its core, PJS is a genetic disorder with a well-established molecular basis.

Cause/Mechanism	Details	Inheritance/Genetics	Source(s)
STK11/LKB1 Mutation	Germline mutation on chromosome 19p13.3	Autosomal dominant	2, 5, 9, 10
Tumor Suppressor Loss	Loss of kinase function, cell cycle control	Inherited or de novo	2, 9, 11
Variable Expressivity	Different mutations = varied symptoms	Missense vs. null alleles	9
Family History	Can be new (sporadic) or inherited	50% risk to offspring	5, 9, 12

Table 3: Genetic and Causal Factors

STK11/LKB1 Gene Mutation

• Gene Location: The STK11 gene (also known as LKB1) is located on chromosome 19p13.3. It acts as a tumor suppressor by regulating cell growth and polarity.
• Mutation Type: PJS is caused by a germline (inherited) mutation in this gene. Both missense (altered function) and null (complete loss of function) mutations are seen. Null mutations are associated with earlier and more severe symptoms 2, 5, 9, 10.

Inheritance Pattern

• Autosomal Dominant: Each child of an affected individual has a 50% chance of inheriting the mutation. However, up to 25%-45% of cases result from new (de novo) mutations, meaning no prior family history 9, 12.
• Variable Expression: Even within a family, the severity and types of symptoms can differ, influenced by the specific mutation and possible modifying factors 9.

Mechanism of Disease

The mutation in STK11 leads to loss of its tumor-suppressing function, allowing abnormal growths (hamartomatous polyps) and increasing the risk of various cancers. This gene also plays a role in fertility, ovarian function, and spermatogenesis, explaining some of the syndrome’s reproductive associations 2, 9, 11.

Treatment of Peutz Jeghers Syndrome

Managing PJS is multidimensional, focusing on treating immediate complications, preventing cancer, and supporting quality of life. Advances in endoscopic techniques and surveillance have transformed outcomes for many patients.

Approach	Focus/Method	When Indicated	Source(s)
Polypectomy	Endoscopic or surgical removal of polyps	Symptomatic or large	12, 15
Surveillance	Regular GI, pancreatic, other screening	Lifelong, all patients	7, 11, 12, 13
Surgery	For obstruction, intussusception, cancer	Emergencies/complicated	3, 4, 15
Cancer Screening	Colon, breast, pancreas, gyn, testicle	Per guidelines	7, 8, 12, 13
Genetic Testing	STK11 mutation analysis	Diagnosis/family	2, 9, 12

Table 4: Main Treatment and Management Strategies

Endoscopic and Surgical Management

• Polypectomy: The cornerstone of treatment is the removal of GI polyps, which can be done endoscopically (using colonoscopy or double-balloon enteroscopy) or surgically for larger or inaccessible growths. Early and regular removal prevents complications such as bleeding, obstruction, and intussusception 12, 15.
• Surgical Intervention: Occasionally, emergency surgery is necessary for acute bowel obstruction, intussusception, or when malignancy is detected. Advances in endoscopic techniques now allow many polyps to be removed without surgery, reducing the risk of short bowel syndrome 3, 4, 15.

Surveillance Protocols

• GI Tract: Regular upper and lower endoscopy is recommended to detect and remove new polyps before they cause symptoms 11, 12, 13.
• Pancreas: Annual or biennial imaging (MRI or endoscopic ultrasound) is advised due to the high risk of pancreatic cancer 7, 8, 11, 13.
• Breast and Gynecologic: Women need regular breast exams, mammography, and pelvic ultrasound. Cervical cancer screening is also essential 7, 8, 13.
• Testicular Exams: Boys and young men should undergo routine testicular exams and ultrasound for early tumor detection 2, 11.

Genetic Counseling and Family Screening

• Genetic Testing: Confirming a STK11 mutation allows for presymptomatic diagnosis and testing of at-risk relatives, enabling early surveillance and intervention 2, 9, 12.
• Family Education: Relatives should be informed about inheritance patterns, cancer risks, and the importance of regular follow-up.

Supportive Care

• Anemia Management: Chronic bleeding may require iron supplementation or transfusions.
• Fertility Counseling: Given reproductive risks, patients may benefit from endocrinology or fertility specialist input 2.

Emerging and Future Therapies

While current treatments focus on surveillance and surgical/endoscopic management, research into the molecular pathways of PJS may eventually lead to targeted medical therapies 11.

Conclusion

Peutz-Jeghers Syndrome is a complex, inherited disorder that demands lifelong attention and a multidisciplinary approach. Its vivid pigmentation, GI polyps, and cancer risk make early recognition and comprehensive management essential. Advances in genetics and endoscopic care have improved outcomes, but ongoing surveillance and research remain critical.

Key points:

• Early clues: Mucocutaneous pigmentation and GI symptoms should prompt consideration of PJS, especially in young patients.
• Genetic basis: Caused by mutations in the STK11/LKB1 tumor suppressor gene, with autosomal dominant inheritance.
• Wide variation: Symptoms and risks vary, including rare tumors in the ovaries and testes.
• Cancer risk: Marked increase in GI and non-GI cancers; requires strict, lifelong surveillance.
• Treatment: Relies on regular endoscopic polypectomy, cancer screening, and genetic counseling for families.
• Future directions: Ongoing research into targeted therapies and optimized surveillance protocols is vital for improving patient outcomes.

With timely diagnosis and proactive care, individuals with Peutz-Jeghers Syndrome can manage risks and live fulfilling lives.