Cargando…

OR22-02 PTEN Hamartoma Tumor Syndrome in Pediatrics: Triggers for Evaluation and the Value of Surveillance

Context: PTEN Hamartoma Tumor Syndrome (PHTS) comprises a collection of rare clinical disorders characterized by germline mutations in the tumor suppressor gene PTEN. Current guidelines recommend screening for thyroid tumors beginning in pediatric age at the time of PHTS diagnosis; however, the bene...

Descripción completa

Detalles Bibliográficos
Autores principales: Baran, Julia, Tsai, Steven, Singleton, Daniel, Isaza, Amber, Brodeur, Garrett, MacFarland, Suzanne, Zelley, Kristin, Mamula, Petar, Bauer, Andrew Jacob
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7209534/
http://dx.doi.org/10.1210/jendso/bvaa046.859
_version_ 1783531100720594944
author Baran, Julia
Tsai, Steven
Singleton, Daniel
Isaza, Amber
Brodeur, Garrett
MacFarland, Suzanne
Zelley, Kristin
Mamula, Petar
Bauer, Andrew Jacob
author_facet Baran, Julia
Tsai, Steven
Singleton, Daniel
Isaza, Amber
Brodeur, Garrett
MacFarland, Suzanne
Zelley, Kristin
Mamula, Petar
Bauer, Andrew Jacob
author_sort Baran, Julia
collection PubMed
description Context: PTEN Hamartoma Tumor Syndrome (PHTS) comprises a collection of rare clinical disorders characterized by germline mutations in the tumor suppressor gene PTEN. Current guidelines recommend screening for thyroid tumors beginning in pediatric age at the time of PHTS diagnosis; however, the benefit of early surveillance has not been well defined. Patients/Objective: We conducted a retrospective, single-site cohort investigation of patients followed at the Children’s Hospital of Philadelphia with diagnosis of PHTS between January 2003 - June 2019. In total, 81 patients under 18 years of age were identified. Clinical features, PTEN mutation codon, thyroid and gastrointestinal (GI) features were extracted from the electronic health record. The aim of the study is to assess genotype-phenotype, the incidence of thyroid and gastrointestinal disease, and to determine whether current recommendations for thyroid surveillance are improving outcomes. Results: The most common clinical feature at presentation was macrocephaly (85%) followed by impaired development (42%), skin/oral lesions (31%), and autistic spectrum disorder (27%). GI polyps were the presenting feature in 5 patients, with 14 of 81 patients ultimately diagnosed secondary to constipation (71%), rectal bleeding (64%), and/or abdominal pain (50%). All polyps were benign. A total of 58 of 81 patients underwent thyroid surveillance, with 30 patients (52%) found to have a nodule(s). Ultimately, 16 patients underwent thyroidectomy, with 31% (5/16) diagnosed with thyroid cancer. All thyroid cancer patients were greater than 10 years of age at diagnosis and all displayed low-invasive behavior (ATA low-risk). Of the patients &lt 10 years at the time of thyroid ultrasound (US) surveillance, 74% (14/19) had a normal US. The remaining five patients who underwent thyroid surgery all had benign histology. No genotype-phenotype relations were found; however, patients with identical mutations were found to have similar clinical features. Conclusions: Patients with macrocephaly associated with impaired development, skin/oral lesions, thyroid nodules and/or early onset GI polyps should undergo germline testing for PHTS. There does not appear to be a clinical advantage to initiating thyroid US surveillance prior to 10 years of age. Early detection may not improve outcome of thyroid cancer as the majority of thyroid cancers display low-invasive behavior. In PHTS patients with a normal physical exam, thyroid ultrasound surveillance can be delayed until after 10 years of age. Early onset GI polyps may be the presenting diagnosis of PHTS.
format Online
Article
Text
id pubmed-7209534
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-72095342020-05-13 OR22-02 PTEN Hamartoma Tumor Syndrome in Pediatrics: Triggers for Evaluation and the Value of Surveillance Baran, Julia Tsai, Steven Singleton, Daniel Isaza, Amber Brodeur, Garrett MacFarland, Suzanne Zelley, Kristin Mamula, Petar Bauer, Andrew Jacob J Endocr Soc Pediatric Endocrinology Context: PTEN Hamartoma Tumor Syndrome (PHTS) comprises a collection of rare clinical disorders characterized by germline mutations in the tumor suppressor gene PTEN. Current guidelines recommend screening for thyroid tumors beginning in pediatric age at the time of PHTS diagnosis; however, the benefit of early surveillance has not been well defined. Patients/Objective: We conducted a retrospective, single-site cohort investigation of patients followed at the Children’s Hospital of Philadelphia with diagnosis of PHTS between January 2003 - June 2019. In total, 81 patients under 18 years of age were identified. Clinical features, PTEN mutation codon, thyroid and gastrointestinal (GI) features were extracted from the electronic health record. The aim of the study is to assess genotype-phenotype, the incidence of thyroid and gastrointestinal disease, and to determine whether current recommendations for thyroid surveillance are improving outcomes. Results: The most common clinical feature at presentation was macrocephaly (85%) followed by impaired development (42%), skin/oral lesions (31%), and autistic spectrum disorder (27%). GI polyps were the presenting feature in 5 patients, with 14 of 81 patients ultimately diagnosed secondary to constipation (71%), rectal bleeding (64%), and/or abdominal pain (50%). All polyps were benign. A total of 58 of 81 patients underwent thyroid surveillance, with 30 patients (52%) found to have a nodule(s). Ultimately, 16 patients underwent thyroidectomy, with 31% (5/16) diagnosed with thyroid cancer. All thyroid cancer patients were greater than 10 years of age at diagnosis and all displayed low-invasive behavior (ATA low-risk). Of the patients &lt 10 years at the time of thyroid ultrasound (US) surveillance, 74% (14/19) had a normal US. The remaining five patients who underwent thyroid surgery all had benign histology. No genotype-phenotype relations were found; however, patients with identical mutations were found to have similar clinical features. Conclusions: Patients with macrocephaly associated with impaired development, skin/oral lesions, thyroid nodules and/or early onset GI polyps should undergo germline testing for PHTS. There does not appear to be a clinical advantage to initiating thyroid US surveillance prior to 10 years of age. Early detection may not improve outcome of thyroid cancer as the majority of thyroid cancers display low-invasive behavior. In PHTS patients with a normal physical exam, thyroid ultrasound surveillance can be delayed until after 10 years of age. Early onset GI polyps may be the presenting diagnosis of PHTS. Oxford University Press 2020-05-08 /pmc/articles/PMC7209534/ http://dx.doi.org/10.1210/jendso/bvaa046.859 Text en © Endocrine Society 2020. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Pediatric Endocrinology
Baran, Julia
Tsai, Steven
Singleton, Daniel
Isaza, Amber
Brodeur, Garrett
MacFarland, Suzanne
Zelley, Kristin
Mamula, Petar
Bauer, Andrew Jacob
OR22-02 PTEN Hamartoma Tumor Syndrome in Pediatrics: Triggers for Evaluation and the Value of Surveillance
title OR22-02 PTEN Hamartoma Tumor Syndrome in Pediatrics: Triggers for Evaluation and the Value of Surveillance
title_full OR22-02 PTEN Hamartoma Tumor Syndrome in Pediatrics: Triggers for Evaluation and the Value of Surveillance
title_fullStr OR22-02 PTEN Hamartoma Tumor Syndrome in Pediatrics: Triggers for Evaluation and the Value of Surveillance
title_full_unstemmed OR22-02 PTEN Hamartoma Tumor Syndrome in Pediatrics: Triggers for Evaluation and the Value of Surveillance
title_short OR22-02 PTEN Hamartoma Tumor Syndrome in Pediatrics: Triggers for Evaluation and the Value of Surveillance
title_sort or22-02 pten hamartoma tumor syndrome in pediatrics: triggers for evaluation and the value of surveillance
topic Pediatric Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7209534/
http://dx.doi.org/10.1210/jendso/bvaa046.859
work_keys_str_mv AT baranjulia or2202ptenhamartomatumorsyndromeinpediatricstriggersforevaluationandthevalueofsurveillance
AT tsaisteven or2202ptenhamartomatumorsyndromeinpediatricstriggersforevaluationandthevalueofsurveillance
AT singletondaniel or2202ptenhamartomatumorsyndromeinpediatricstriggersforevaluationandthevalueofsurveillance
AT isazaamber or2202ptenhamartomatumorsyndromeinpediatricstriggersforevaluationandthevalueofsurveillance
AT brodeurgarrett or2202ptenhamartomatumorsyndromeinpediatricstriggersforevaluationandthevalueofsurveillance
AT macfarlandsuzanne or2202ptenhamartomatumorsyndromeinpediatricstriggersforevaluationandthevalueofsurveillance
AT zelleykristin or2202ptenhamartomatumorsyndromeinpediatricstriggersforevaluationandthevalueofsurveillance
AT mamulapetar or2202ptenhamartomatumorsyndromeinpediatricstriggersforevaluationandthevalueofsurveillance
AT bauerandrewjacob or2202ptenhamartomatumorsyndromeinpediatricstriggersforevaluationandthevalueofsurveillance