Complications of Childhood Peutz-Jeghers Syndrome: Implications for Pediatric Screening

Peutz-Jeghers syndrome (PJS) is an autosomal dominant condition characterized by hamartomatous gastrointestinal polyps and mucocutaneous pigmentation. Polyps are found predominantly in the small bowel but also in the stomach and colon. The primary concern to the pediatrician is the development of small bowel intussusception and obstruction, and the object of pediatric surveillance of affected individuals is the prevention or amelioration of these complications. In affected kindreds, an early diagnosis is nearly always possible because perioral and mucosal pigmentation is found in 95% of affected individuals (1). On the other hand, genetic markers have been less useful in the clinical context. Although a defective gene (2) has been identified in some cases (LKB1, also called STK11, which is located on chromosome 19q13.3), not all affected individuals have been found to have a mutation in this gene. Board-man et al. (3) found mutations in only 6 of 33 cases, and significant variation in the severity of clinical manifestations has been reported in those cases with an identifiable genotype (4). Various protocols to assess the presence of small bowel polyps have been reported. These may soon require modification with the advent of newer techniques, such as wireless capsule endoscopy, which may allow better visualization of the small bowel. Reviewing the published data concerning the natural history of PJS and its complications in childhood reveals a striking lack of information on the most basic descriptive data, such as the frequency of obstructive complications or the age at which such complications could be expected. MATERIALS AND METHODS The St. Mark’s Hospital Polyposis Registry is a resource that offers an opportunity to collect such natural history data. Staff began collecting data more than 70 years ago on PJS and other polyposis syndromes. The Registry now constitutes the largest prospectively collected database of individuals with PJS. In this study, we used this database to describe the natural history of PJS in childhood, with particular reference to intra-abdominal complications. Our object was to inform the debate as to when, how, and how often children from affected families should undergo screening for polyps. A review of information in The Registry concerning all individuals affected with PJS and the evaluated family members was performed. A structured questionnaire was sent to all identified individuals in an attempt to validate the data. Information regarding age at presentation and timing of episodes of gastrointestinal complications or laparotomies before the age of 18 years was sought. RESULTS We identified 32 kindreds in The Registry among whom there were 51 individuals affected with PJS. Thirty-four were older than 18 years (median age, 34 years). There was a progressive increase in the percentage of patients requiring a laparotomy for a PJS complication throughout the childhood years (Fig. 1). The questionnaire response rate was 94%. There was excellent concordance between The Registry and the questionnaire. The recall for the year of laparotomy in two individuals was inaccurate by 1 and 2 years, respectively.FIG. 1.: Percentage of all PJS patients avoiding laparotomy in their childhood years.In this study, 23 of 34 (68%) adults with PJS had undergone a laparotomy for an episode of intestinal obstruction before they reached 18 years of age (3.8% per year; median time from diagnosis to first laparotomy, 10 years; range, 2–17 years). Seventy percent of the initial laparotomies were performed urgently for intestinal obstruction. After the initial laparotomy, 39% (9/23) of the individuals with intestinal obstruction before the age of 18 years had a second laparotomy within 5 years for a polyp-related complication. Of these, two occurred within the first year and three within the second year after laparotomy. DISCUSSION The natural history of children with PJS has not been well characterized. Consequently an evidence-based approach to screening has been hard to establish. This study has some inevitable weaknesses, namely the difficulty in separating true emergencies from semielective operations for large symptomatic polyps. Despite these reservations, it is still the largest report to date of intra-abdominal complications in childhood and can provide reference data from which to develop screening protocols. The aims of screening in this population should be the identification of children at risk for intestinal obstruction from small bowel polyps so that the polyps can be removed by enteroscopy or elective laparotomy with intra-operative enteroscopy. Preventative removal of polyps may reduce the rate of emergency surgery being performed in nonspecialist units. Surgery performed in these circumstances is less likely to be performed by appropriately trained pediatric teams and may be associated with increased rates of morbidity and mortality. Furthermore, emergency surgery outside centers with pediatric gastroenterology experience may not include enteroscopy at the time of laparotomy, which has been shown to reduce reoperation rates (5). Based on our clinical impressions, rather than this more systematic review of the natural history of PJS in childhood, we have previously proposed a screening regimen of regular small intestinal contrast radiology (6). The data from this study confirm the potential benefit of a relatively early start for such a program, perhaps between 5 and 10 years of age. By the age of 10 years, 30% of subjects had already required a laparotomy. We would recommend performing screening at the younger end of this age range for children with symptoms. Otherwise, in non-symptomatic cases, 8 years of age seems appropriate. The progressive increase in laparotomies with age means that after the initial assessment screening will need to be repeated at regular intervals (we suggest every 2 years). Such repeat assessment with contrast radiology could be open to debate in view of the resulting cumulative radiation dosage. The capsule endoscopy (7) which is rapidly being applied in pediatric patients will probably become the screening tool of choice in time. However, the minimum age and size criteria for this diagnostic modality still need to be defined. The management of symptomatic polyps should be elective laparotomy with intra-operative enteroscopy in specialist pediatric centers. For asymptomatic polyps, we recommend that a similar approach be adopted where polyps are of significant size (> 1 cm), particularly when pedunculated. Otherwise, repeat screening should be performed within 2 years or sooner if symptoms arise. The impact of screening on the overall clinical outcome unfortunately will be difficult to quantify because the condition is rare and the time scales involved are prolonged. Its role in asymptomatic cases will be even more difficult to ascertain, particularly in the context of the current lack of data on such cases. However, this study does highlight the value of meticulous long-term data collection from registries such as that at St. Mark’s Hospital. In practice, these registries represent one of the few sources of evidence that can be used to inform policy decisions, particularly when considering rare inherited diseases. Acknowledgments: The authors thank Kay Neale and Professor R. K. Phillips of The Polyposis Registry.