Peutz-Jeghers Syndrome in Resource-Limited Scenario

Abstract

BACKGROUND: Peutz-Jeghers Syndrome (PJS) is a rare, autosomal dominant disease, caused by deletions in the chromosome 19p33.3/ gene LKB1/STK11. These mutations inactivate a serine/threonine kinase and predispose to carcinogenesis. In PJS, tumors of the gastrointestinal, testicles, pulmonary, breast, pancreas, uterus and ovaries can be found. OBJECTIVE: To evaluate demographics, clinical presentation and complication/outcomes of pediatric patients presenting with Peutz-Jeghers syndrome (PJS), as well as to present and discuss management in the context of limited resources. METHODS: We conducted a retrospective chart review of a cohort of six patients, who were diagnosed and/or followed at the Clinics Hospital, University of Campinas - Sao Paulo/Brazil, between 2000 and 2018. Data analyzed included gender, age of presentation, age of diagnosis, family history, PJS complications. RESULTS: Median age of diagnosis of 6.7 years, with a mean time of follow-up of 8.1 years. Mucocutaneous pigmentation was universally present. Half of the patients had a known family history at the time of diagnosis. On follow up, intestinal intussusception was documented in four out of six patients, in most (three), in different locations and in multiple occasions. The active investigation of siblings and parents of the index case led to the diagnosis of three first-degree relatives in the present case series. CONCLUSION: In this first pediatric PJS Brazilian case series, we report a wide spectrum of PJS manifestations and complications. In a resource limited scenario, despite limitations for the surveillance of complications, the relative frequency of complications was not higher than historically reported.

Oral pigmented lesions in syndromic individuals: A systematic review

“…It is important to highlight that patients with PJS exhibit an increased incidence of gastrointestinal carcinoma as well as genital and mammary tumors (Latchford et al., 2019). Therefore, an early diagnosis of PJS allows the practitioner to anticipate guidance, manage complications, and provide early treatment (Sandy et al., 2020). The diagnosis is based on clinical findings, and the affected individual should have at least two of the three listed clinical criteria for a positive diagnosis: (1) family history; (2) multiple dark blue or brown pigmented (macules) lesions on the mucous membranes and skin, intraoral lesions on the buccal mucosa or gingiva, lips and perioral area, as well as lesions on the fingertips, palms, and soles; (3) hamartomatous intestinal polyps (Wu & Krishnamurthy, 2020).…”

“…It is important to highlight that patients with PJS exhibit an increased incidence of gastrointestinal carcinoma as well as genital and mammary tumors (Latchford et al, 2019). Therefore, an early diagnosis of PJS allows the practitioner to anticipate guidance, manage complications, and provide early treatment (Sandy et al, 2020). McCune-Albright syndrome is a distinctive form of endocrine and non-endocrine neoplasia caused by a postzygotic mutation of the GNAS1 gene, with affected cells being distributed in a mosaic pattern (Ringel et al, 1996).…”

“…Peutz–Jeghers syndrome represented the second most frequent syndrome in this systematic review. This condition comprises a rare autosomal dominant disorder characterized by multiple gastrointeintestinal hamartomatous polyps with an increased risk of cancer and typical mucocutaneous pigmentation (Sandy et al., 2020; Wu & Krishnamurthy, 2020). In agreement with the findings of our systematic review, white women ≤ 19 years of age were more affected.…”

Peutz-Jeghers syndrome

“…Compared to capsule enteroscopy, magnetic resonance enterography provides higher specificity and comparable sensitivity in the diagnosis of small bowel lesions generally [49]. The reliability of both methods in the detection of larger (>10 mm) polyps is comparable in Peutz-Jeghers syndrome [50], and their use depends mainly on local experience and availability [51]. Complementary use of both diagnostic methods can be useful and increase the amount of information before the use of more invasive procedures.…”

Clinical criteria for Peutz-Jeghers syndrome diagnosis: Look for what is missing

“…More investigations for all the family members as well as genetic study were indicated. Discussion Clinical diagnosis of Peutz-Jeghers syndrome is confirmed in the following situations: three or more histologically confirmed Peutz-Jeghers polyps, any number of Peutz-Jeghers polyps with family history of Peutz-Jeghers syndrome, characteristic mucocutaneous pigmentation with a family history of Peutz-Jeghers syndrome, any number of Peutz-Jeghers polyps and characteristic mucocutaneous pigmentation [3]. Small bowel intussusception in PJS is widely described in the literature [4].…”