Peutz–Jeghers–Touraine syndrome: signs and management

Peutz-Jeghers-Touraine syndrome is a rare hereditary condition characterized by hamartomatous polyps of the gastrointestinal tract and characteristic mucocutaneous pigmentation (dark freckles on the lips, oral mucosa, fingers, and perianal area). The disease is caused by germline variants in the STK11 (also LKB1) gene and is inherited in an autosomal dominant manner. Some patients have sporadic (de novo) mutations or mosaicism. The disease is associated with a significantly increased risk of malignant tumors later in life. [1]

Polyps are most commonly located in the small intestine (in descending order: jejunum, ileum, duodenum), but can also be found in the stomach and colon, as well as in extraintestinal locations. Clinically, they lead to bleeding, anemia, abdominal pain, and episodes of intussusception, especially in childhood and adolescence. Characteristic pigmentation usually appears in childhood and may partially fade after puberty. [2]

The primary medical goal in this syndrome is not only to monitor polyps and prevent complications (such as intussusception), but also to effectively organize lifelong monitoring for oncological risks. Current European and North American guidelines detail intervals for endoscopic monitoring of the stomach, intestines, and small intestine, and also describe when and how to discuss pancreatic and breast screening. [3]

Despite its rarity, information on the syndrome is rapidly evolving: European guidelines (EHTG) were published in 2021, the ESPGHAN position paper on pediatric management was published in 2019, and reviews and practice notes were updated in 2024–2026. In this version of the article, all sections and tables have been verified against the latest open-access sources. [4]

Code according to the International Classification of Diseases, 10th and 11th revisions

The International Classification of Diseases, Eleventh Revision, provides a separate code for Peutz-Jeghers syndrome, LD2D.0. A separate section in the International Classification of Diseases, Eleventh Revision, emphasizes the hereditary, hamartomatous nature of the polyps and the associated increased risk of cancer, which simplifies accounting and registries. [5]

The International Classification of Diseases, Tenth Revision, does not have a specific entry for the syndrome name, so the section "Other phakomatoses" is used—code Q85.89 (in some reference books, it is listed as Q85.8 with clarification), which is officially used for Peutz-Jeghers syndrome. Additionally, when recording an episode of care, procedural and "organ" codes are often added (for example, K63.5—colon polyp), but the primary code for the syndrome is Q85.89. [6]

Table 1. Diagnosis coding

System	Code	Name	Comment
ICD 11	LD2D.0	Peutz-Jeghers syndrome	Specific heading of the International Classification of Diseases, Eleventh Revision
ICD 10 (CM)	Q85.89	Other phakomatoses, not elsewhere classified	Recommended code for Peutz-Jeghers
Additional "organ" codes	K63.5 / K31.7 and others.	Intestinal/stomach polyps	Used as an adjunct to a specific episode

[7]

Epidemiology

Peutz-Jeghers syndrome is rare: the prevalence is estimated at 1 in 50,000-200,000, and in some sources - up to 1 in 25,000-300,000. The disease affects people of both sexes and all ethnic groups. Up to 50-80% of families have a detectable pathogenic variant in STK11. [8]

The age of onset varies: pigmentation usually appears in the first years of life, while symptomatic polyps and intussusceptions often occur in adolescence and early adulthood. This determines the low threshold for early diagnosis and preventive endoscopic interventions in pediatric practice. [9]

The overall lifetime risk of any cancer is significantly elevated. According to systematic reviews and cohorts, the overall lifetime risk ranges from 37% to 93%, with relative risks to the general population being approximately 10-18. Not only the magnitude of the risks is important, but also their "rejuvenation": many tumors occur before the age of 40-50. [10]

The highest cumulative risks are for breast cancer in women, colorectal cancer, pancreatic cancer, gastric cancer, and tumors of the genital organs (including sex cord tumors of the ovary and Sertoli tumors in boys). This justifies multidisciplinary monitoring (gastroenterology, gynecologic oncology, mammology, genetics). [11]

Table 2. Epidemiological landmarks

Indicator	Meaning
Prevalence	1 in 50,000-200,000 (according to some sources 1 in 25,000-300,000)
Genetics	Autosomal dominant type, STK11 is found in 50-80% of families
Age of debut	Pigmentation in childhood, polyps/intussusceptions - adolescents/young adults
Lifetime risk of any cancer	37-93% (10-18 times increase over the population)

[12]

Reasons

The only reliably confirmed cause of the syndrome is germline pathogenic variants in the STK11 gene (locus 19p13.3), which encodes a serine/threonine kinase involved in the regulation of cell polarity, energy metabolism, and signaling via the AMPK-mTOR pathway. This is a typical tumor suppressor gene: loss of function facilitates tumor transformation in a number of tissues. [13]

Transmission is autosomal dominant with high phenotypic penetrance but variable expression. De novo cases and low-level parental mosaicism have been described, which is important to consider in genetic counseling and risk assessment for offspring. [14]

Genotype-phenotype correlations are moderate: different types of mutations (nonsense/frameshift vs. missense) influence the age of symptom manifestation but do not strictly predict cancer risks for a given patient. This justifies a universal screening approach regardless of the variant type. [15]

The tumor microenvironment and additional "second hits" (e.g., somatic mutations in KRAS, TP53, PTEN) contribute to carcinogenesis. This explains the wide spectrum of tumors and their sometimes earlier age of onset compared to the general population. [16]

Risk factors

The main factor is the presence of a germline variant of STK11. However, family history is not required: up to half of individuals may be the first in the family due to a de novo mutation or mosaicism, but their children will have a 50% risk of inheriting the variant. [17]

Gender does not protect against the syndrome, but the cancer risk profile in women includes a high probability of breast cancer and gynecological tumors, which requires a separate monitoring route (mammologist, gynecologist-oncologist). [18]

Childhood and adolescence are independent factors for complications of the small intestine (intussusception), therefore children and adolescents require proactive endoscopic/radiological monitoring of the small intestine and timely electro/endoscopic polypectomy. [19]

Smoking and chronic metabolic factors are generally unfavorable for carcinogenesis, but no specific risk modifiers comparable in strength to the influence of STK11 have been identified in Peutz-Jeghers syndrome; however, compliance with screening programs has proven beneficial. [20]

Pathogenesis

Loss of STK11 function disrupts the control of cell growth, polarity, and metabolism; through the AMPK-mTOR axis, proliferation is enhanced and hamartomatous polyps are formed. These polyps are morphologically benign but can cause clinically significant complications (bleeding, anemia, obstruction, intussusception). [21]

Carcinogenesis in this syndrome is multifocal and multiorgan. The risk is increased in the gastrointestinal tract (colon, stomach, small intestine, pancreas) and outside it (mammary gland, genitals), which requires lifelong multi-screening programs. [22]

Small intestinal polyps, especially large ones, often serve as a "mechanical" link in complications, leading to intussusception, the most common emergency problem in young people. Preventive measures include removing polyps of a certain size and monitoring the small intestine using capsule imaging or magnetic resonance imaging. [23]

Additional "second hits" in tumor genes against the background of the STK11 defect accelerate the development of dysplasia and malignancies. This explains the observed "degree of rejuvenation" of cancer risk. [24]

Symptoms

The most recognizable symptom is dark brown/bluish-brown spots on the lips, oral mucosa, around the nostrils, eyes, and perianal area; they are also common on the fingers. These spots appear in childhood, sometimes partially lightening after puberty, but serve as an important diagnostic "beacon" when combined with intestinal symptoms. [25]

Intestinal manifestations include episodes of abdominal pain, bleeding, iron deficiency anemia, and bloating; in children and adolescents, small bowel intussusception with vomiting and a picture of acute intestinal obstruction is typical. Repeat laparotomies, previously performed, are now more often prevented by planned endoscopic removal of polyps. [26]

In men, gynecomastia may occur due to hormonally active Sertoli cell tumors; in women, it may be due to menstrual irregularities and ovarian sex cord tumors. With age, the risk of stomach, colon, pancreatic, and breast cancer increases. [27]

Some patients remain asymptomatic for a long time; in such cases, the syndrome is detected by pigmentation or family screening/genetic testing. This further emphasizes the value of early genetic diagnosis in families with a known mutation. [28]

Table 3. Clinical clues

Block	Examples	What does it give to a doctor?
Mucocutaneous pigmentation	Spots on the lips/in the mouth/perianally	Early "red mark" in a child
Intestinal symptoms	Pain, bleeding, anemia, intussusception	Threshold for endoscopy and MR/capsule evaluation of the small intestine
Extraintestinal signs	Gynecomastia, sex cord tumors	Reasons for cancer screening by gender and age
Family history	Relatives with polyps/spots/cancer at a young age	Indication for STK11 testing

[29]

Classification, forms and stages

There is no universal "staging," but in practice, the phenotype is described along three axes: 1) polyp process activity (frequency of symptoms, need for interventions), 2) polyp burden by gastrointestinal tract (stomach/small intestine/colon), 3) cancer risk profile and the presence of dysplasia. This stratification helps select observation intervals. [30]

Based on age, a distinction is made between a childhood-adolescent phenotype with a risk of intussusception and an adult phenotype with an increase in cancer risks, particularly of the breast and pancreas. This is reflected in separate guidelines for children (ESPGHAN) and adults (EHTG, NCCN). [31]

In terms of genetics, cases with confirmed STK11 mutation and clinically diagnosed cases without an identified variant are discussed - surveillance strategies for both groups are similar, given the comparable risks. [32]

A number of sources use practical gradations based on the size of polyps (for example, thresholds of 10-15-20 mm for the decision on removal) and the frequency of bleeding episodes/“suspected intussusception” to form endotherapy tactics. [33]

Table 4. Practical phenotyping

Axis	Categories	What changes tactics
Age	Children/teenagers - adults	Start time and frequency of examinations
The Burden of Polyps	Stomach / small intestine / large intestine	Choice of imaging method and polypectomy threshold
Oncological factors	Dysplasia, familial cancer cases, female gender	Involvement of a mammologist/gynecologist, pancreatic screening
Genetics	STK11+ / no identified mutation	Equally rigorous screening

[34]

Complications and consequences

In young patients, the key problem is intussusception of the small intestine due to large polyps, which may require emergency intervention; prevention is provided by planned endoscopic removal of polyps and targeted monitoring of the small intestine. [35]

In the adult cohort, the main burden is oncological risks: colorectal cancer, gastric cancer, pancreatic cancer, breast cancer, and sex cord tumors. Timely screening programs reduce mortality and the incidence of late-stage disease. [36]

Iron deficiency anemia and chronic blood loss impair exercise tolerance and quality of life, requiring not only the removal of “bleeding” polyps, but also persistent correction of iron deficiency and nutritional support. [37]

Repeated bowel surgeries (in the absence of prophylactic endotherapy) can lead to adhesions and short bowel syndrome. Current recommendations emphasize the priority of an organ-preserving, endoscopic strategy. [38]

When to see a doctor

If a child or adult develops characteristic spots on the lips/in the mouth, along with abdominal pain, intestinal bleeding, or episodes of obstruction, a consultation with a gastroenterologist with experience in hereditary polyposis is necessary. Genetic counseling and STK11 testing expedite diagnosis. [39]

Urgent medical attention is required for signs of intussusception/obstruction (paroxysmal pain, vomiting, absence of stool and gas), melena/blood in the stool, and severe weakness associated with anemia. These conditions require urgent imaging and, often, emergency endoscopy. [40]

Women with the syndrome need scheduled visits to a mammologist and gynecological oncologist, and if there is a family history of pancreatic cancer, a discussion of early screening at a specialized center. [41]

First-degree relatives of patients with identified STK11 mutations are recommended to undergo cascade testing and, if positive, to be included in a surveillance program from childhood. [42]

Diagnostics

The first step is a clinical and anamnestic assessment and physical examination: characteristic pigmentation, family history of early oncological diseases, episodes of intussusception. A complete blood count (anemia), ferritin, biochemistry, and, if necessary, tests for occult blood are prescribed. [43]

The second step is an endoscopic "passport" examination of the stomach and colon with polypectomy of accessible large polyps. For the small intestine, capsule endoscopy and/or magnetic resonance enterography are chosen; if polyps requiring removal are identified, balloon-assisted enteroscopy is planned. [44]

The third step is molecular genetic testing for STK11 in an accredited laboratory (blood/saliva). A positive result confirms the diagnosis and initiates a cascade testing program within the family; if a negative result is obtained, the clinical diagnosis remains in the typical presentation, and screening is not relaxed. [45]

The fourth step is to develop an individualized monitoring plan: intervals for gastroscopy and colonoscopy, small bowel monitoring, referral to a mammologist/gynecologist, and discussion of pancreatic screening at a center with experience in managing high-risk groups. [46]

Table 5. Diagnostic supports

Direction	What are we looking for?	Why is it important?
Examination and anamnesis	Pigmentation, family history of cancer, intussusception	Generates a "pre-test" probability
Endoscopy	Polyp mapping + targeted polypectomy	Prevention of bleeding/intussusception
Small bowel assessment	Capsule and/or MR enterography	Search for "problem" polyps in the small intestine
Genetics	Pathogenic variant of STK11	Confirmation of diagnosis and cascade testing

[47]

Differential diagnosis

Peutz-Jeghers syndrome is distinguished from other hamartomatous polyposis disorders: juvenile polyposis (BMPR1A/SMAD4), Cowden syndrome/PTEN hamartomatous syndrome, and familial adenomatous polyposis (APC). Peutz-Jeghers syndrome is characterized by mucocutaneous pigmentation and polyps of a specific structure, while other syndromes have different phenotypes and genes. [48]

"Common" hyperplastic/inflammatory polyps without a family history and without pigmentation, as well as polyposis "due" to chronic inflammation, should be excluded. Morphology and genetics are decisive here, as is the polyp distribution map (predominance of the small intestine in Peutz-Jeghers syndrome). [49]

In children, it is differentiated from diseases causing intussusception without polyposis (eg, Wirsungolithiasis/mesenteric factors), but the presence of multiple polyps and pigmentation quickly shifts the diagnosis in favor of Peutz-Jeghers. [50]

The second major issue is the distinction from other hereditary cancer syndromes, where pancreatic/mammary screening tactics may differ. A number of centers are developing standardized "screening maps" for all carriers of high-risk genes, adapting them to the specific gene. [51]

Table 6. Differential series

State	What is "for"?	What's against?	How to check
Peitz-Jeghers	Pigmentation + hamartomas of the small intestine + familial	The absence of STK11 mutation does not exclude	STK11 Genetics, Polyp Map
Juvenile polyposis	Multiple juvenile polyps	No characteristic pigmentation	Genetics of BMPR1A/SMAD4
PTEN-hamartoma	Papillomas, macrocephaly, skin signs	Another clinic	PTEN Genetics
Familial adenomatous	Hundreds of colon adenomas	Different type of polyps, different genetics	APC Genetics

[52]

Treatment

The basic management strategy is the prevention of mechanical complications involving the small intestine and the reduction of oncological risks through organized screening. During the active phase, endoscopic polypectomy and removal of "leading" polyps with a high risk of intussusception are used for multiple and large polyps; this allows the situation to be transitioned from an emergency to a planned one. In children and adolescents, this tactic significantly reduces the risk of surgery. [53]

Capsule endoscopy and/or magnetic resonance enterography are used to map the small intestine. If large lesions are detected (usually 10-15-20 mm), a double- or single-balloon enteroscopy with polyp removal is planned. In specialized centers, staged elimination of the "risk pool" over several sessions is possible. [54]

Gastroscopy and colonoscopy are performed regularly, with polyp removal, dysplasia monitoring, and biopsy of suspicious areas. European guidelines (EHTG/ESGE) emphasize that examinations should be performed in centers with experience in polyp syndromes and quality indicators for endoscopy (completeness of examination, complete removal, documentation). [55]

There is no drug-based "anti-polyp" therapy with proven long-term effectiveness; the role of mTOR inhibitors is discussed in the context of individual tumors and studies, but this is not the standard for polyp prevention. The primary focus is timely endotherapy and screening for high-risk target organs. [56]

Pancreatic screening remains a topic of debate: current consensus suggests discussing it in specialized centers starting at approximately 30–35 years of age (or 10 years younger than the earliest family history), using annual MRCP and/or endoscopic ultrasound. The decision is personalized based on family history and resource availability. [57]

For women with this syndrome, breast cancer risk counseling is essential: starting at age 30, annual magnetic resonance imaging of the mammary glands with contrast and mammography, as well as clinical examinations every 6-12 months; preventive surgery is discussed individually. For gynecological tumors, annual examinations and ultrasound monitoring are recommended based on high-risk recommendations. [58]

Nutritional support and correction of iron and vitamin deficiencies are an important part of care, especially after multiple polypectomies and in cases of blood loss. This improves the tolerability of endoscopic procedures and quality of life, and reduces the need for transfusions and hospitalizations. [59]

Surgical interventions are indicated for complications that are not amenable to endotherapy (unstoppable bleeding, obstruction that cannot be corrected endoscopically, suspected invasive cancer) and should be maximally organ-preserving, taking into account the risk of a short bowel. Preoperative polyp mapping reduces the incidence of "unexpected" residual lesions. [60]

Non-gastrointestinal cancer screening is an integral part of the surveillance plan: for the mammary gland, pelvic organs, and, if there is a family history, for the pancreas. Management is coordinated by a multidisciplinary team (geneticist, gastroenterologist, endoscopist, radiologist, oncologists of various specialties, and a pediatrician/internist). [61]

Patient and family education is another "treatment tool": recognizing the symptoms of intussusception, understanding the goals and timing of screening, and the importance of cascade testing of first-degree relatives. Support and reminder programs increase adherence to lifelong monitoring, which directly impacts long-term outcomes. [62]

Table 7. Endoscopic tactics and monitoring

Direction	Method	Basic intervals (guidelines)	Key points
Colon	Colonoscopy	From the age of 18, every 2-3 years (more often with multiple polyps)	Removal of polyps, dysplasia control
Stomach	Esophagogastroduodenoscopy	From 18 years old every 2-3 years	Biopsies of suspicious areas
Small intestine	Capsule ± MR enterography; targeted enteroscopy	From 8-10 years, then every 2-3 years/based on findings	Polypectomy at size thresholds
Quality	Polyposis centers	Constantly	ESGE: Endoscopy quality is critical

[63]

Prevention

There is no primary prevention for the syndrome, as it is caused by an inherited variant of STK11. However, secondary prevention of complications is extremely effective: early detection and planned removal of polyps significantly reduce the risk of intussusception and emergency surgery in children and young adults. [64]

At the level of oncological risks, "prevention" is achieved through competent screening and timely diagnosis of precancerous changes—endoscopic examinations, a mammography program, and discussion of pancreatic screening at experienced centers. Adherence to monitoring is a key factor. [65]

Family-based cascade testing allows for the identification of carriers before symptoms appear and their inclusion in the ESPGHAN child monitoring program (starting at 8-10 years of age). This reduces the risk of emergency situations and improves the family's long-term quality of life. [66]

Lifestyle (smoking cessation, weight control, physical activity) is beneficial but does not compensate for genetic risk; it may reduce overall cancer burden and improve the tolerability of interventions, and is therefore included in the recommendations. [67]

Forecast

In the absence of organized surveillance, the overall lifetime risk of any cancer is very high, reaching 37–93% according to systematic reviews; tumors often develop at a young age. The implementation of polyp screening and endotherapy programs significantly improves long-term outcomes. [68]

Cumulative risks vary by organ: according to large series and reviews, by the age of 60–70 years, the highest risks are for breast cancer (up to 54%), colon (about 39%), pancreatic (up to 36%), stomach (about 29%), and ovarian (about 21%). These figures vary between studies, but the trend is stable. [69]

Early diagnosis and prophylactic polypectomy reduce the incidence of intussusception and surgical interventions; follow-up with specialists in hereditary polyposis is associated with better outcomes and fewer complications. [70]

The individual prognosis depends on the age at which observation begins, the polypectomies performed, the quality of endoscopy, and adherence to mammological/gynecological/pancreatic monitoring. With good adherence to the program, patients live long, active lives. [71]

Table 8. Approximate cumulative risks (guidelines based on open sources)

Localization	Lifetime risk assessment*	Typical ages
Any cancer	37-93%	Young and middle age
Mammary gland (women)	up to 54%	30-60 years old
Colon	about 39%	30-60 years old
Pancreas	up to 36%	30-70 years old
Stomach	about 29%	30-60 years old
Ovaries	about 21%	20-50 years old

* Estimates vary between studies and depend on methodology.[72]

FAQ

Is it always inherited?
Yes, classically – autosomal dominant with a 50% risk for offspring. However, de novo mutations and mosaicism are possible, so there may be no family history. Genetic testing for STK11 clarifies the situation. [73]

Is pancreatic screening necessary for everyone?
This is decided on an individual basis in experienced centers. Current consensus recommends discussing annual MRCP and/or endoscopic ultrasound starting at age 30–35, or 10 years younger than the age of the previous family history, if any. [74]

At what age should children be examined?
Initial assessment of the stomach, colon, and small intestine begins at 8-10 years of age; then at 2-3 year intervals, or more frequently, based on findings and symptoms. This approach reduces the risk of intussusception and emergency surgery. [75]

What codes should be included in the patient's chart?
The International Classification of Diseases, Eleventh Revision uses LD2D.0 (specific). The International Classification of Diseases, Tenth Revision uses Q85.89 "Other phakomatoses," as well as "organ" codes as appropriate (e.g., K63.5 for colon polyp). [76]

Table 9. Summary observation plan (adults and adolescents)

Authority/Direction	Start	Interval	Methods
Colon	18 years old	2-3 years (more often with multiple polyps)	Colonoscopy, polypectomy
Stomach	18 years old	2-3 years	Esophagogastroduodenoscopy, biopsy if indicated
Small intestine	8-10 years	2-3 years/based on findings	Capsule, MR enterography, balloon enteroscopy
Mammary gland (women)	30 years old	Annually	Magnetic resonance imaging with contrast + mammography
Pancreas*	30-35 years old	Annually	MRCP and/or endoscopic ultrasound
Gynecology	18-20 years old	Annually	Examination, ultrasound, cytology

* In a specialized center after informed discussion. [77]