Juvenile polyposis of the colon, Weil's syndrome: features

Juvenile polyposis (JPP) is a rare, autosomal dominant inherited disorder in which multiple hamartomatous "juvenile" polyps develop throughout the gastrointestinal tract. The term "juvenile" refers to the histologic type of polyp, not the patient's age; however, most people develop their first polyps before age 20. The primary sites of occurrence are the colon and rectum, and less commonly the stomach and small intestine. [1]

The clinical spectrum is extremely variable: in some families, the lifetime polyp count among different members ranges from 4-5 to over 100. Juvenile polyps are essentially benign, but the syndrome increases the risk of malignant tumors, primarily colorectal cancer, and if the stomach is affected, gastric cancer. This dictates mandatory observation and timely endoscopic treatment. [2]

The underlying cause is germline variants in genes involved in the transforming growth factor beta signaling pathway, most commonly SMAD4 and BMPR1A. Carriers of the SMAD4 variant may have a phenotypic overlap with hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome), necessitating expanded screening for vascular manifestations. [3]

Current guidelines emphasize early genetic testing in at-risk families, regular colonoscopy and esophagogastroduodenoscopy, and an individualized polyp removal strategy. For massive polyps that are not accessible by endoscopic sanitation, surgical options are considered; however, with proper monitoring, most patients benefit from organ-preserving care. [4]

Code according to ICD-10 and ICD-11

In the International Classification of Diseases, Tenth Revision, the clinical code for juvenile polyposis syndrome is D12.6 "Benign neoplasm of colon, unspecified," with additional diagnostic detail (e.g., "juvenile polyposis syndrome"). Alternatively, colon polyp(s) are recorded as K63.5 in symptomatic cases, or history/family history codes are used for routing purposes. The choice of a specific code depends on local reporting regulations. [5]

The International Classification of Diseases, Eleventh Revision, includes a category for "Polyposis Syndrome" (2E92.40) with post-coordination, allowing for the addition of features of the hereditary syndrome and clarification of anatomy (large intestine). This approach is consistent with the logic of ICD-11, where detail is achieved through code clusters. Some reference books map juvenile polyposis to ICD-11 as "polyposis syndrome"; it is recommended to use the official ICD-11 browser with post-coordination. [6]

Table 1. Practical coding

Classifier	Basic code	What to include in the diagnosis text
ICD-10	D12.6	Juvenile polyposis syndrome; colon polyps
ICD-10 (alternative, depending on the situation)	K63.5; Z83.71; Z86.010	Colon polyp; family or personal history of polyps
ICD-11	2E92.40 (+ post-coordination)	Polyposis syndrome; clarify the hereditary nature and localization

Explanation: ICD is a statistical tool; for clinical routing and insurance, morphology and genetic status are also important, but they are reflected in the descriptive part, and not always in the code. [7]

Epidemiology

Juvenile polyposis is a rare syndrome; the estimated incidence is approximately 1 in 100,000 population, although estimates vary due to differences in detection and study design. Most patients present before age 20, but diagnosis is often made later, with the development of bleeding or anemia. [8]

In familial cohorts, up to 40-60% of cases are explained by pathogenic variants in SMAD4 or BMPR1A. Some patients have no detectable changes in these genes even with complete sequencing and analysis of large deletions/duplications, indicating genetic heterogeneity. The proportion of de novo variants is estimated at approximately 20-30%. [9]

The risk of colorectal and gastric cancer in carriers varies from 9% to 50%, according to published data, and depends on the genotype, polyp burden, and quality of follow-up. Gastric involvement is particularly pronounced in carriers of the SMAD4 variant, requiring a targeted gastroscopic strategy. [10]

Registry data and guidelines of recent years are shifting tactics towards early screening of families, regular colonoscopy and endoscopic sanitation, which allows for a reduction in surgical activity and oncological risks. [11]

Table 2. Epidemiological landmarks

Indicator	Grade
Frequency in the population	≈ 1 in 100,000
The proportion of SMAD4/BMPR1A among confirmed JPS	40%-60%
Share of de-novo variants	20%-30%
Lifetime risk of gastrointestinal cancer	9%-50% (higher with SMAD4)

Reasons

Key causes are germline pathogenic variants in SMAD4 and BMPR1A, components of the transforming growth factor-beta and bone morphogenetic protein signaling pathways. These variants disrupt the control of proliferation and apoptosis in the mucosa, predisposing to hamartomatous polyps. [12]

A combined phenotype of "juvenile polyposis and hereditary hemorrhagic telangiectasia" (JP-HHT) has been described in SMAD4 variant carriers, necessitating screening for telangiectasias, epistaxis, and visceral arteriovenous malformations. Any identified SMAD4 mutation is considered a risk factor for JP-HHT until proven otherwise. [13]

Not all patients show changes in SMAD4/BMPR1A - other, as yet rare, genes and regulatory regions are likely involved; this does not exclude a clinical diagnosis and does not cancel out monitoring according to guidelines. [14]

Inheritance is autosomal dominant, with a 50% risk of transmitting the variant to offspring in each pregnancy. Mosaicism and incomplete penetrance explain the clinical diversity within families. [15]

Risk factors

The main factor is a family history of juvenile polyposis or early colorectal/gastric tumors; in such families, genetic counseling and testing of adults and adolescents is recommended. Identifying an index carrier allows for the development of an individualized screening plan for relatives. [16]

Factors influencing clinical manifestation include genotype (SMAD4 vs. BMPR1A), polyp burden, and associated inflammatory changes in the mucosa; an increase in the number and size of polyps increases the risk of bleeding and anemia. [17]

SMAD4 carriers have increased gastric involvement; with age, the lesion tends to progress from the cardia to the body and antrum, which justifies more frequent gastroscopy. [18]

General population factors (smoking, obesity, low-fiber diet) are not the primary cause of the syndrome, but may modify the course and recovery after interventions, so standard lifestyle recommendations remain appropriate.[19]

Pathogenesis

Juvenile polyps (hamartomas): proliferation of glandular epithelium with dilated crypts against a background of inflammation and edema of the lamina propria. Histologically, this distinguishes them from adenomas, but with chronic inflammation and multiple polyps, the likelihood of dysplasia increases. [20]

Signaling through BMPR1A/SMAD4 regulates the balance of crypt proliferation and differentiation. Loss of function leads to mucosal hyperplasia and architectural disruption, which clinically manifests as multiple polyps and a tendency to bleed. [21]

In the SMAD4-associated phenotype, vascular structures are involved—telangiectasias, nosebleeds, and arteriovenous malformations appear. This explains the need for multidisciplinary monitoring (gastroenterologist, geneticist, ENT specialist, phlebologist/angiologist). [22]

Long-standing large polyps may ulcerate, become infected, and create conditions for anemia and nutritional deficiency; timely endoscopic sanitation and nutritional correction reduce these risks. [23]

Symptoms

The most common manifestations are rectal bleeding, mucous discharge, alternating constipation and diarrhea, and lower abdominal pain. Prolonged bleeding leads to iron deficiency anemia with weakness and shortness of breath during exertion. In some patients, polyps are discovered incidentally during screening endoscopy. [24]

With massive polyposis, polyp prolapse through the anus, tenesmus, and signs of partial intestinal obstruction are possible. Bleeding can be both overt and latent; therefore, in cases of unexplained anemia, colonoscopy is indicated. [25]

Gastric polyps present with epigastric discomfort, nausea, early satiety, and, if ulcerated, malnutrition. In the SMAD4 variant, gastrointestinal symptoms may be accompanied by nosebleeds and telangiectasias of the skin/mucous membranes. [26]

In children and adolescents, warning signs include blood on toilet paper, recurrent abdominal pain, and failure to gain weight; if there is a family history, these signs require prompt evaluation. [27]

Classification, forms and stages

A distinction is made between "juvenile polyposis coli" (polyps limited to the colon) and "generalized juvenile polyposis" (polyps in the upper and lower sections). The diagnostic criteria of the World Health Organization include one of three: ≥5 juvenile polyps in the colon/rectum; multiple juvenile polyps throughout the gastrointestinal tract; any juvenile polyps with a positive family history. [28]

Genetically, SMAD4-associated and BMPR1A-associated variants are conventionally distinguished; the former more often results in gastric polyps and overlap with hereditary hemorrhagic telangiectasia. This influences the examination plan and observation intervals. [29]

Staging, as with tumors, is not used; instead, the polyp burden (number, size, distribution), presence of dysplasia, blood loss, and nutritional status are assessed. These parameters determine the management strategy, from observation to endoscopic debridement or surgery. [30]

The age of onset, family history and associated polyposis syndromes (for differential diagnosis with Peutz-Jeghers syndrome, Cowden syndrome, etc.) are also taken into account. [31]

Table 3. Diagnostic criteria for juvenile polyposis (WHO)

Criterion	It is sufficient for diagnosis if at least one is present
≥5 juvenile polyps in the colon/rectum	Yes
Multiple juvenile polyps throughout the gastrointestinal tract	Yes
Any juvenile polyps + family history of JPS	Yes

Complications and consequences

The most common complications are chronic blood loss with iron deficiency anemia, polyp prolapse, ulceration and inflammation of the mucosa, and, less commonly, intussusception and partial obstruction. These complications most often occur with large and multiple polyps. [32]

Oncologic risks include colorectal cancer and gastric cancer; their magnitude depends on genotype, polyp burden, age, and quality of follow-up. Early polyp removal and strict endoscopic monitoring reduce these risks. [33]

In the SMAD4-associated phenotype, vascular complications of hereditary hemorrhagic telangiectasia are added—nosebleeds, iron deficiency due to chronic bleeding, arteriovenous malformations of the lungs/liver/brain. This requires multidisciplinary management. [34]

Psychosocial consequences include frequent endoscopies, fear of cancer, and limitations in daily activities; patient and family education, access to genetic counseling, and support are part of the standard of care. [35]

When to see a doctor

Immediately - in case of rectal bleeding, melena, severe weakness or dizziness due to anemia, abdominal pain with suspected obstruction. These symptoms require urgent endoscopic and laboratory evaluation. [36]

Routine screening is recommended for recurring mucus discharge, changes in stool, unexplained anemia, or weight loss. Genetic counseling should be considered if there is a family history of juvenile polyposis or early colorectal/gastric cancer. [37]

Children and adolescents from risk families are recommended to start endoscopic monitoring and genetic testing early if indicated - this helps prevent complications and delay or avoid surgery. [38]

After polyp removal, a schedule of follow-up endoscopies and correction of deficiencies (iron, vitamin B12, folates) should be followed, agreeing on the frequency of visits with the treatment team. [39]

Diagnostics

The first step is to confirm the phenotype: colonoscopy with a comprehensive examination and removal of visible polyps with histological examination; if there are complaints above, esophagogastroduodenoscopy. In children/adolescents and if a generalized process is suspected, this procedure is expanded to bilateral endoscopic screening. [40]

The second step is a laboratory assessment of anemia (complete blood count, ferritin, iron, transferrin), nutritional deficiencies, and inflammation. If indicated, a fecal occult blood test, stool analysis, and malabsorption markers may be performed. [41]

The third step is genetic testing (JPS panel: SMAD4, BMPR1A; with analysis of large rearrangements). A positive result helps with cascade testing in the family and influences the surveillance plan (especially for SMAD4). The absence of an identified variant does not exclude JPS if the clinical criteria are met. [42]

The fourth step is the development of an endoscopic surveillance plan: starting at 12-15 years of age or earlier if symptoms occur; colonoscopy and gastroscopy every 1-3 years depending on the polyp burden, increasing to annual frequency in the case of multiple polyps and reducing to every 3 years for “clean” examinations. [43]

Table 4. Diagnostic algorithm

Stage	Action	Target
1	Colonoscopy ± EGDS with removal of polyps	Phenotype confirmation, treatment
2	Laboratory (anemia, deficiencies)	Correction of complications
3	Genetics (SMAD4, BMPR1A)	Verification, family screening
4	Observation plan 1-3 years	Prevention of complications and cancer

Differential diagnosis

Juvenile polyposis is distinguished from other hereditary polyposis conditions: Peutz-Jeghers syndrome (hamartomas with dendritic muscular stroma and STK11 mutations), Cowden syndrome/PTEN hamartoma syndromes, and familial adenomatous polyposis (hundreds of adenomas, APC). Morphology and genetics are the key to an accurate diagnosis. [44]

JPS differs from solitary juvenile polyps of childhood (often sporadic and not associated with cancer) in the number of lesions, family history, and polyp burden. Solitary polyps generally do not require long-term follow-up outside the context of familial risk. [45]

Juvenile hamartomas differ from inflammatory and hyperplastic polyps in the architecture of the crypts and stroma; if in doubt, repeat histology at a reference center is decisive. [46]

In SMAD4 carriers, it is important to differentiate bleeding from polyps and from telangiectasias of the upper sections; if suspected, endoscopy with targeted hemostasis and consultation with HHT are recommended. [47]

Table 5. How JPS differs from other polyposis

Syndrome	Morphology	Genetics	Peculiarities
Juvenile polyposis	Hamartomas with dilated crypts	SMAD4/BMPR1A	Risk of colon and stomach cancer
Peitz-Jeghers	Branched muscular stroma	STK11	Lip pigmentation, small intestinal intussusception
Familial adenomatous polyposis	Adenomas (hundreds)	APC	Very high risk of cancer, colproctectomy

Treatment

The basic strategy is endoscopic debridement: removal of clinically significant polyps with histological control and mapping. For multiple polyps, a staged approach with separate procedures is used to reduce the risk of complications and properly manage anemia. Preoperative correction of iron deficiency improves tolerability. [48]

The frequency of control endoscopies depends on the polyp burden: in the case of multiple polyps and rapid recurrences - annually; in the case of rare findings after sanitation - every 2-3 years. The stomach is simultaneously assessed: in SMAD4 - more frequently, due to the tendency for gastric lesions to progress. [49]

Genetic counseling is standard: cascade testing of adult first-degree relatives; for children in families with JPS, monitoring begins at 12-15 years of age or earlier if symptoms develop. Variant detection allows for personalized endoscopy intervals and the scope of examinations. [50]

Surgery is indicated for uncontrolled polyp burden, high-grade multiple dysplasia, or recurrent complications that are not remediable endoscopically. Preference is given to organ-preserving surgeries (segmental colectomy) based on foci mapping; total colectomy is reserved for extreme polyposis and intractable complications. Postoperative follow-up is essential, as polyps may develop in the stump and upper sections. [51]

In patients with the SMAD4-associated phenotype, additional monitoring is performed using HHT protocols: ENT examination, pulmonary screening for arteriovenous malformations, echocontrast examination, and, if necessary, embolization. This reduces the risk of sudden vascular complications. [52]

There is no specific drug therapy for JPS; anti-inflammatory and antiproliferative strategies discussed in studies do not yet replace endoscopy/surgery. Therapy is aimed at correcting deficiencies (iron, folate, vitamin B12), nutritional support, and treating complications. [53]

Management tactics for children: gentle removal techniques, minimization of anesthetic risk, coordination with a pediatric gastroenterologist. Examination intervals in children are more frequent, especially in the first years after manifestation, with a gradual reduction when the picture is stable. [54]

In cases of severe gastric polyposis (most often SMAD4), the strategy may include frequent endoscopic resections; gastrectomy is an extremely rare measure when sanitation is unavailable and severe complications arise. The decision is made by a consultation involving a gastroenterologist, a geneticist, and an anesthesiologist. [55]

An important part is patient education: recognizing the signs of blood loss, rules for preparing for endoscopy, and the role of family testing. A written "patient passport" with genotype, endoscopy dates, and center contact information improves adherence and safety. [56]

Finally, if high-grade dysplasia or adenocarcinoma is suspected, the oncological standard applies: staging imaging, discussion at a clinical-oncological council, and determination of the extent of resection/adjuvant therapy according to local protocols. A juvenile background does not exclude "adenomatous" carcinoma. [57]

Table 6. Control and interventions

Situation	Action	Interval
Multiple polyps after sanitation	Colonoscopy ± EGDS	1 year
Small polyp burden	Colonoscopy ± EGDS	2-3 years
SMAD4, expressed gastric component	EGDS	1 year (or more often according to the clinic)
Uncontrolled polyposis/dysplasia	Consultation, surgery	Individually

Prevention

There is no specific "primary prevention" for the syndrome, as it is hereditary. Prevention of complications lies in early identification of affected families, genetic counseling, and regular endoscopies with polyp removal. Informing first-degree relatives is key. [58]

Lifestyle recommendations: adequate fiber intake, alcohol limitation, smoking cessation, and weight management. These do not negate the genetic component, but they improve the tolerability of interventions and help manage deficiencies. [59]

In SMAD4, vascular complications are prevented using HHT protocols (prevention of mucosal bleeding, iron deficiency monitoring, and screening for arteriovenous malformations). Patients are given an action plan for nosebleeds and red flag signs. [60]

Families are offered psychological support and a “patient school” to improve adherence to care and reduce anxiety about cancer risks. [61]

Forecast

Prognosis is largely determined by the quality of follow-up and genotype. With regular endoscopic sanitation and appropriate screening intervals, most patients live with a good quality of life, avoiding severe bleeding and reducing cancer risks. [62]

The SMAD4-associated phenotype requires more vigilant gastric monitoring and screening for HHT-related complications, while early detection and treatment of vascular malformations significantly improves outcomes. [63]

Surgical interventions allow control of polyp burden when endoscopy is ineffective, but are associated with the risk of functional consequences; therefore, a staged endoscopic approach is preferred whenever possible. [64]

Overall, as genetics and screening protocols are implemented, the prognosis for patients with JPS improves, particularly with cascade testing in families and centralized surveillance.[65]

Additional tables for practice

Table 7. Recommendations for the start and frequency of monitoring

Age/situation	What to do	Frequency
12-15 years in risk families or earlier if symptoms appear	Colonoscopy + EGDS	Start; further on the burden of polyps
"Clean" colonoscopy after sanitation	Colonoscopy	Every 2-3 years
Multiple polyps	Colonoscopy	Annually
SMAD4 carrier	EGDS	Annually

Table 8. Genetics and phenotype

Gene	Share among JPS	Typical features
SMAD4	≈ 20%-30% of all JPS; together with BMPR1A - 40%-60%	Prominent gastric polyps, overlap with HHT
BMPR1A	The rest of the pair is SMAD4/BMPR1A	Mainly colorectal polyps

Table 9. Coding and documents

Task	What to indicate
ICD-10	D12.6 + description "juvenile polyposis syndrome"
ICD-11	2E92.40 "Polyposis syndrome" + postcoordination
Anamnesis	Z83.71 "family history of colon polyps"; Z86.010 "personal history"

Table 10. Red flags in favor of JPS

Sign	Why is it important?
≥5 juvenile polyps in the colon	WHO criterion
Polyps in the upper and lower sections	Generalized JPS
Family history of JPS/early cancer	The basis for genetics
Epistaxis/telangiectasias (SMAD4)	Suspicion of JP-HHT

FAQ

1) Is this a "childhood" disease?
No. "Juvenile" is a histological type of polyp. Symptoms often appear before age 20, but JPS is also diagnosed in adults; lifelong monitoring is required. [66]

2) Is surgery always necessary?
No. The basis is regular endoscopic debridement. Surgery is considered in cases of uncontrolled polyp burden, high dysplasia, or complications not amenable to endoscopy. [67]

3) How often should colonoscopy and EGD be performed?
Typically, they start at 12-15 years of age, or earlier if symptoms occur, then every 1-3 years depending on the polyps; for multiple polyps, they are performed annually; for "clean" examinations, they are performed every 2-3 years. For SMAD4, gastroscopy is performed more frequently. [68]

4) Does everyone need genetic testing?
It is recommended for patients with clinical criteria for JPS and first-degree relatives. Identification of the SMAD4/BMPR1A variant helps plan family surveillance and screening. A negative result does not rule out JPS. [69]