Dataset Information

A Bi-Institutional Study of Gastrointestinal and Hepatic Manifestations in Children With PTEN Hamartoma Tumor Syndrome.

ABSTRACT:

Background and aims

PTEN hamartoma tumor syndrome (PHTS) confers a high risk of specific cancers and is the most common genetic cause of autism spectrum disorder (ASD). Gastrointestinal (GI) phenotypes in PHTS are poorly characterized in children. Thus, we aimed to characterize the GI and hepatic manifestations in children with PHTS and to investigate genotype-phenotype associations.

Methods

We performed a retrospective chart review of prospectively accrued children with PHTS at 2 tertiary-care centers. Wilcoxon rank-sum, Chi-squared, and Fisher's exact tests and Firth's logistic regression were utilized to explore associations between variables.

Results

This series included 80 children with disease-causing PTEN variants. Common GI manifestations included constipation in 41 (51%), feeding issues in 31 (39%), and polyps in 22 (28%) children. The polyps were of mixed histologic types. Eosinophilic gastrointestinal disorders were observed in 5 (6%) children. Crohn's disease, celiac disease, and protein-losing enteropathy were observed once each. Eosinophilic gastrointestinal disorders were observed exclusively in patients without ASD (P = .052). Nonsense PTEN variants were enriched in those with polyps (P = .029). Missense PTEN variants (OR 2.9, P = .034) and upper GI polyps (OR 4.4, P = .018) were associated with increased odds of constipation.

Conclusion

Constipation and feeding issues are common in children with PHTS. Polyps are more prevalent in children with PHTS than previously described and associated with nonsense PTEN variants. Children without ASD represent a distinct patient subset with a predisposition to eosinophilic gastrointestinal disorders and possibly upper GI polyps. Endoscopic evaluation should continue to be performed in symptomatic children with PHTS, with consideration of closer follow-up in those without ASD.

SUBMITTER: Liu D

PROVIDER: S-EPMC11307957 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

A Bi-Institutional Study of Gastrointestinal and Hepatic Manifestations in Children With <i>PTEN</i> Hamartoma Tumor Syndrome.

Liu Darren D MacFarland Suzanne P SP Yehia Lamis L Duvall Melani M MM Mamula Petar P Kurowski Jacob A JA Greene Colleen S CS Radhakrishnan Kadakkal K Eng Charis C

Gastro hep advances 20231031 2

<h4>Background and aims</h4><i>PTEN</i> hamartoma tumor syndrome (PHTS) confers a high risk of specific cancers and is the most common genetic cause of autism spectrum disorder (ASD). Gastrointestinal (GI) phenotypes in PHTS are poorly characterized in children. Thus, we aimed to characterize the GI and hepatic manifestations in children with PHTS and to investigate genotype-phenotype associations.<h4>Methods</h4>We performed a retrospective chart review of prospectively accrued children with PH ...[more]

PMID: 39129943

Similar Datasets

Project description:BackgroundPTEN hamartoma tumor syndrome (PHTS) represents a group of syndromes caused by a mutation in the PTEN gene. Children with a germline PTEN mutation have an increased risk of developing differentiated thyroid carcinoma (DTC). Several guidelines have focused on thyroid surveillance in these children, but studies substantiating these recommendations are lacking.ObjectiveThe present study intends to provide the available evidence for a thyroid carcinoma surveillance program in children with PHTS.MethodsAn extensive literature search was performed to identify all studies on DTC in pediatric PHTS patients. Two pediatric cases are presented to illustrate the pros and cons of thyroid carcinoma surveillance. Recommendations for other patient groups at risk for DTC were evaluated. Consensus within the study team on recommendations for children with PHTS was reached by balancing the incidence and behavior of DTC with the pros and cons of thyroid surveillance, and the different surveillance methods.ResultsIn 5 cohort studies the incidence of DTC in childhood ranged from 4 to 12%. In total 57 cases of DTC and/or benign nodular disease in pediatric PHTS patients were identified, of which 27 had proven DTC, with a median age of 12 years (range 4-17). Follicular thyroid carcinoma (FTC) was diagnosed in 52% of the pediatric DTC patients. No evidence was found for a different clinical behavior of DTC in PHTS patients compared to sporadic DTC.ConclusionsChildren with PHTS are at increased risk for developing DTC, with 4 years being the youngest age reported at presentation and FTC being overrepresented. DTC in pediatric PHTS patients does not seem to be more aggressive than sporadic DTC.RecommendationsSurveillance for DTC in pediatric PHTS patients seems justified, as early diagnosis may decrease morbidity. Consensus within the study team was reached to recommend surveillance from the age of 10 years onwards, since at that age the incidence of DTC seems to reach 5%. Surveillance for DTC should consist of yearly neck palpation and triennial thyroid ultrasound. Surveillance in children with PHTS should be performed in a center of excellence for pediatric thyroid disease or PHTS.