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Original Articles: Gastroenterology

Polyp Progression in Paediatric Patients With Familial Adenomatous Polyposis: A Single-centre Experience

Anele, Chukwuemeka C.∗,†,‡; Xiang, Jinpo§; Martin, Isabel∗,||; Hawkins, Menna; Clark, Susan K.∗,||; Faiz, Omar D.∗,‡,||; Latchford, Andrew∗,||; Hyer, Warren

Author Information
Journal of Pediatric Gastroenterology and Nutrition: November 2020 - Volume 71 - Issue 5 - p 612-616
doi: 10.1097/MPG.0000000000002845


What Is Known/What Is New

What Is Known

  • Familial adenomatous polyposis is an autosomal dominant inherited polyposis syndrome leading to formation of adenomas in childhood and adolescents.
  • The phenotype is confirmed by colonoscopy commencing in the early teenage years but the ideal frequency of colonoscopy in teenager cohort has not been previously investigated.

What Is New

  • This is the first study to identify the natural history of familial adenomatous polyposis in a paediatric cohort <18 years, specifically looking at polyp progression over time.
  • The frequency of colonoscopies no longer needs to be annual and can be personalized depending on polyp burden.

An infographic is available for this article at:

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited condition characterized by the development of hundreds to thousands of adenomatous polyps in the colon and rectum. Progression to colorectal cancer (CRC) is inevitable if left untreated (1). The management of children with, or at risk of, FAP is based around appropriate timing of predictive genetic testing, endoscopic surveillance and prophylactic colectomy (colectomy and ileorectal or ileodistal sigmoid anastomosis [IRA]) or proctocolectomy (usually restorative, with formation of ileoanal pouch [RPC]) at a premalignant stage. Adenomas generally begin to be detected in adolescence, with some studies reporting a mean age of 16 years at first identification of polyps of (2–4). The number and size of the adenomas are thought to be dependent on factors including genotype (location of pathogenic variant in the adenomatous polyposis coli [APC] gene) and age at which the large bowel is examined (5,6).

Published guidelines recommend regular colonoscopic surveillance to assess for the adenoma number, size, and distribution (7,8). Although endoscopic surveillance has been shown to reduce the risk of CRC in patients with FAP (9), optimal frequency remains contentious. Some authors recommend yearly colonoscopy in all children under surveillance once adenomas have been identified (6,10), whereas recent guidelines recommend adopting an individualized approach based on the patient's genotype and phenotype (11,12). Similar controversies exist with regard to timing of prophylactic surgery. Generally, indications for surgery include onset of colorectal symptoms, marked increase in polyp size or number, presence of high-grade dysplasia, and patient's choice (8,13). There is, however, no consensus on the exact age, size, or polyp number at which surgery should be offered or which surgical procedure should be performed. Some centres recommend colectomy once adenomas have been identified while others recommend colectomy at a time that when it will cause minimal disruption to the child's psychological, social, and educational development. It is generally agreed that in those with a milder genotype (pathogenic variant outside the mutation cluster region [MCR]) and phenotype (<500 colonic polyps and <20 rectal polyps), it is reasonable to delay surgery and perform IRA (14,15).

Evidently, there are controversies in the management of paediatric patients with FAP in terms of optimum intervals for colonoscopy surveillance and timing of prophylactic colectomy. Our aim was to better understand the natural history of FAP in this group of patients by evaluating adenoma progression and factors influencing the timing of colectomy.


This study was approved by our institutional review board as a service evaluation project. At our institution, predictive genetic testing for children at risk of FAP (where there is a known constitutional pathogenic variant in an affected family member) is recommended at the age of 12 to 14 years. Colonoscopy surveillance is commenced if they are proven to be mutation carriers. In those with a family history of FAP but no identified pathogenic variant, screening colonoscopy at the age 14 to 15 years is recommended. Colonoscopies in children are usually performed under general anaesthetic by a paediatric gastroenterologist. Colorectal adenoma burden is calculated by counting number of adenomas on withdrawal, or if adenomas are too numerous to count individually, it is estimated as previously described in the literature (16). Adenoma size was estimated relative to the open biopsy forceps (17,18). Polypectomy is not routinely performed in children at our institution.

The prospectively maintained St Mark's Hospital Polyposis Registry was searched to identify all patients with FAP under the age of 18 years at their first surveillance colonoscopy. FAP diagnosis was defined as confirmed APC pathogenic variant on genetic testing or the presence of histologically confirmed adenomas on colonoscopy in an individual with known family history of clinically diagnosed FAP. Data from the Polyposis Registry were supplemented with data from patients’ medical, endoscopic, pathology, and operative records. Data extracted include demographic information, family history, genetic results (location of pathogenic variant in APC), dates and frequency of endoscopic surveillance, endoscopic findings (number of polyps at each colonoscopy), and type of surgery (eg, IRA or RPC), age at surgery, and indication for surgery.

To adequately assess adenoma progression, we excluded patients who had undergone only 1 colonoscopy, patients followed up at other institutions, and colonoscopy reports without a numerical adenoma count.


To facilitate analysis of genotype, the pathogenic APC variant was stratified based on the location relative to the MCR (codon 1250–1450). The groups were group 1, pre-MCR (5’ of codon 1250); group 2, MCR (codon 1250–1464); group 3, post-MCR (3’ of 1464); and group 4, gross deletion. The increase in absolute colorectal adenoma (polyp) counts count per year for each individual was calculated relative to the polyp count at previous colonoscopy, using the formula “rate of polyp progression per year” = (number of polyps documented at a given colonoscopy – polyp count at previous colonoscopy)/(time between colonoscopies [years]). There is currently no evidence to support polyp regression in patients with FAP; therefore, the rate of polyp progression was assumed to be zero if the polyp count at a given colonoscopy was less than the count at previous colonoscopy.

Statistical Analysis

Continuous variables were expressed as mean and standard deviation or median and range depending on distribution. Categorical variables were reported as frequency (percentages). In addition to a summary of the changes in category in different time periods, a statistical comparison between time periods was performed. A feature of the data was that the same patients were assessed over time. Because of the binary nature of the outcome (increase or no increase), the analyses were performed using multilevel binary logistic regression. In patients who showed polyp progression, the rate of polyp progression was calculated as described above. The Mann-Whitney U test was used to compare 2 categories and the Kruskal-Wallis test for >2 categories.



Over the 20-year study period, 142 patients under the age of 18 years with a confirmed diagnosis of FAP were seen at our institution. Of these, 58 were excluded because they were not followed up at our institution (n = 24), only had 1 surveillance colonoscopy (n = 33) or did not have a numerical documented polyp count (n = 1). A total of 84 patients met our inclusion criteria of which 42 (50%) were boys. Eighty-three patients (99%) had known family history of FAP and 1 (1%) had new mutation. All patients had undergone genetic testing of which 62 (74%) had an APC pathogenic variant in the pre-MCR region, 13 (15%) in MCR, 5 (6%) in post-MCR region, and 4 (5%) patients had a gross deletion (Table 1). Forty-five (54%) patients had undergone prophylactic surgery.

Patient demographics

Endoscopic Surveillance and Polyp Progression

A total of 293 colonoscopies were carried out over the study period, of which 210 (72%) were performed by a single paediatric gastroenterologist. The median age at first colonoscopy was 13 (range 9–18). Three patients with mutation in codon 1309 had their first colonoscopy before the age of 11 years due to onset of colorectal symptoms. Adenomas were identified in 77 (92%) patients at initial colonoscopy. In 29 (35%) patients, polyps were identified in colon despite rectal sparing. At first colonoscopy 67 (79%) individuals had fewer than 100 polyps, 14 (17%) had between 101 and 500 polyps, and 3 (4%) had over 500 polyps (Table 2). The median adenoma count in the different genotypic groups was pre-MCR 40 (0–400), MCR 75 (15–1000), post-MCR 2 (0–15), and gross deletion 50 (10–60) (P = 0.0547). The median size of the largest adenoma colonoscopy was 3 mm (range 1–15 mm). After a median follow-up of 3.5 (range 2–8) years and median of 3 (range 2–8) colonoscopies per patient, there was a 26% increase in polyp count per year (95% confidence interval: 20%–32%; P < 0.001). The median rate of polyp progression per patient was 12.5 polyps/year (range 0–124). The rate of polyp progression was highest in the MCR group (16 polyps/year [range 5–145]).

Endoscopic surveillance


During the study period, 45 patients had undergone prophylactic surgery of which 27 (60%) were boys. The mean age at surgery was 17 (range 11–22) years and the rate of polyp progression in this group was 13 polyps/year (0–124). The median polyp count in the resected surgical specimen was 178 (3–3150) and no patient was diagnosed with CRC. Forty-one (91%) patients underwent IRA, 3 (7%) underwent RPC and 1 (2%) underwent panproctocolectomy and end ileostomy. Restorative proctocolectomy was performed in 3 patients with 1309 mutation due to presence of severe rectal polyposis and each had total pathology polyp count >1000. All 3 underwent colectomy before the age of 12 years. One patient was scheduled to undergo RPC; however, this was converted to panproctocolectomy and end ileostomy due to the presence mesenteric desmoid. Surgery was mostly (51%) performed as a planned procedure at a time that was least disruptive on the child's social and educational development. The genotype and indications for surgery are summarized in Table 3.

Prophylactic surgery


Our results support the recently published guidelines from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition, which recommend that annual colonoscopy is not required for all children with FAP under surveillance, rather surveillance should be individualized based on colorectal phenotype (11). In addition, polyp progression did not appear to alter the choice of surgical intervention in any patient; the choice of surgery was guided by genotype, colonic phenotype, and rectal polyp burden, which in none of our cases changed sufficiently to alter which operation was recommended. Similar findings were reported in a recent study by Sarvepalli et al (19). They examined the rate of polyposis progression in 168 patients younger than 30 years and found that the rate of polyp progression was independently associated with genotype and polyp number at initial colonoscopy. To our knowledge, our study is the first article to evaluate polyp progression in children with FAP. Other published studies on paediatric patients with FAP have mainly reported on smaller groups of patients or were published before the genetic testing era and therefore may have included patients with other adenomatous polyposis syndromes, where tumour biology may differ.

Current evidence suggests that flexible sigmoidoscopy is inadequate in the assessment of adenoma number and distribution in children with FAP. Previous historical data by Bussey (20) demonstrated rectal involvement in all 170 adult cases with colonic polyposis; however, studies have shown that <80% of children have colonic adenomas at first colonoscopy (21,22). Furthermore, Munck et al (12) demonstrated that at initial colonoscopy, 11% of children were found to have colonic polyposis despite not having any polyp in the rectosigmoid. Similar findings were observed in our study; at a median age of 13 (9–17) years at first colonoscopy, colonic adenomas were identified in 92% of patients in our cohort and 29 (35%) patients had identifiable colonic polyps despite the absence of polyps in the rectum. Consequently, it is unsurprising that some authors (21) and institutions (11) now recommend colonoscopy rather than flexible sigmoidoscopy as an initial screening tool when predictive genetic testing is not available. Our findings further support the evidence that endoscopic surveillance should be by colonoscopy to adequately assess the entire large bowel and define the patient's colorectal phenotype.

Genotypic and phenotypic correlation in FAP have been reported in published studies (23,24). Pathogenic variants in the hotspot regions such as 1309 or between 1250 and 1450 regions are associated with a more severe phenotype and earlier presentation of disease. These phenomena were observed in our study. The median rate of polyp progression/year was lowest in individuals with less severe phenotype: pre-MCR and post-MCR 15.4 (range 0–124), MCR 16 (range 5–145), and gross deletion 10.4 (range 9–31), although this was not statistically significant (P = 0.647). Studies have also described phenotypic variability amongst individuals or families with similar pathogenic variant (22,25,26). For example, although the median age at initial colonoscopy was 13, three patients with pathogenic variant in codon 1309 (associated with severe polyposis) had first colonoscopy before the age of 11 years due to onset of colorectal symptoms; 2 of these patients had >1000 colorectal polyps and 1 had 150 at first colonoscopy. Furthermore, of the 66 patients with less severe genotype (pre-MCR and post-MCR), 7 patients had no identifiable colorectal polyp at initial colonoscopy and the rate of polyp progression in these 7 patients was 1.2 polyps/year. Similar findings were reported in the Cleveland Clinic study (19). They demonstrated a correlation between the rate of polyposis progression, genotype, and polyp count at first colonoscopy. In their study, patients with a pathogenic variant in MCR had the highest of progression whereas the lowest rate were observed in patients with a pathogenic variant 5’ of codon 151 and in those with <20 polyps at first colonoscopy (19). They concluded that low polyp count at first colonoscopy predicts polyposis progression independent of genotype. These genotypic-phenotypic correlation and inter and intrafamilial variability in polyp count has led to some authors recommending individualization of surveillance protocol based on the patient's colorectal phenotype with the genotype providing supportive information (12,21,27). Asymptomatic patients with low polyp burden at initial colonoscopy could be offered a less frequent surveillance compared to those with severe phenotype.

Colectomy remains the definitive management of patients with FAP; however, the optimal age at which surgery should be performed, the magnitude of increase in polyp count at which surgery should be recommended and the choice of surgery remains contentious. Recent guidelines suggest that patients should be referred for colectomy if there is concern about polyp size, density, and presence of advanced changes (11). In our study, only 7% of patient underwent surgery due to polyposis progression. The majority (53%) underwent colectomy as a planned procedure at time that was least disruptive to the child's social educational development. This suggests that the decision for colectomy is not solely dependent on the endoscopic evidence of polyposis progression. This is supported by the fact the rate of polyp progression in the patients who had undergone surgery was only slightly higher than those with intact colon continuing surveillance (13.1 vs 10.8 polyps/year). The other factor contributing to timing of colectomy is patient's or family decision to opt for early colectomy over continuing surveillance despite the individual having no concerning endoscopic features. In the 15 patients who opted for earlier surgery in our cohort, the median preoperative endoscopic polyp count was 43 (range 0–110) and all patients underwent IRA. It is likely that this decision may have been influenced by the surgical outcome in older first-degree relatives who had undergone surgery at similar age. Consequently, we recommend the decision for timing and type of surgery is made by a multidisciplinary team and factors such as genotype, phenotype (colorectal polyp burden and size of polyp), patient's preference, social and educational needs should be considered.

We acknowledge several limitations to our study. This was a single-centre study from a large polyposis registry which is prone to inherent institutional, referral, and data entry biases. For example, our data did not include other factors which may influence polyposis progression and surgical decision making, including but not limited to diet, smoking history, body mass index, family history of desmoid, and size of adenomas. Furthermore, although 72% of the colonoscopies were performed by a single experienced paediatric gastroenterologist, estimation of polyp size and counts especially in cases in which actual numerically count could not be done may have been prone to error. Also, we have assumed a linear relationship in description of the polyp progression over time which may not be entirely accurate.


Our results suggest that polyposis progression is slow in the majority of children under surveillance. The need for annual colonoscopy is not supported and tailoring surveillance interval to phenotype is a more appropriate strategy. Our results support the recently published European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines.


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colonoscopy; colorectal cancer; familial adenomatous polyposis; paediatric patients; surveillance

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