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A Bi-Institutional Study of Gastrointestinal and Hepatic Manifestations in Children With PTEN Hamartoma Tumor
Darren Liu1,2, Suzanne P MacFarland3,4, Lamis Yehia1
1Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Insights
PTEN hamartoma tumor syndrome (PHTS) in children commonly causes constipation and feeding issues. Polyps are more frequent than previously thought and linked to specific PTEN variants, while children without autism spectrum disorder (ASD) may have unique gastrointestinal risks.
Area of Science:
- Genetics and Genomics
- Pediatric Gastroenterology
- Autism Spectrum Disorder Research
Background:
- PTEN hamartoma tumor syndrome (PHTS) is a genetic disorder associated with increased cancer risk and is a leading genetic cause of autism spectrum disorder (ASD).
- Gastrointestinal (GI) manifestations in pediatric PHTS are not well-documented.
- This study aims to detail GI and hepatic issues in children with PHTS and explore genotype-phenotype correlations.
Purpose of the Study:
- To characterize gastrointestinal and hepatic manifestations in children diagnosed with PHTS.
- To investigate the relationship between specific PTEN gene variants and clinical phenotypes in affected children.
- To identify potential differences in GI presentations between children with PHTS with and without ASD.
Main Methods:
- Retrospective chart review of 80 children with pathogenic PTEN variants at two tertiary care centers.
- Statistical analyses including Wilcoxon rank-sum, Chi-squared, and Firth's logistic regression were employed.
- Exploration of associations between GI symptoms, PHTS phenotypes, and PTEN genotype.
Main Results:
- Constipation (51%) and feeding difficulties (39%) were the most common GI issues. Polyps were found in 28% of children, with mixed histology.
- Eosinophilic gastrointestinal disorders (EGIDs) occurred in 6% of patients, exclusively in those without ASD (p=0.052).
- Nonsense PTEN variants correlated with polyps (p=0.029), while missense variants and upper GI polyps were linked to increased constipation risk (p=0.034 and p=0.018, respectively).
Conclusions:
- Constipation and feeding problems are prevalent GI issues in pediatric PHTS.
- The prevalence of polyps in PHTS children is higher than previously reported and associated with specific PTEN variants.
- Children with PHTS without ASD may represent a distinct subgroup with increased risk for EGIDs and upper GI polyps, warranting specific endoscopic surveillance strategies.
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.
