Cerebral MRI and Clinical Findings in Children with PTEN Hamartoma Tumor Syndrome: Can Cerebral MRI Scan Help to Establish an Earlier Diagnosis of PHTS in Children?

Michaela Plamper,Vera Splittstößer,Sandra Schulte,Felix Schreiner,Joachim Woelfle,Bettina Gohlke,Mark Born

doi:10.3390/cells9071668

Michaela Plamper, Vera Splittstößer + Show 5 more

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https://doi.org/10.3390/cells9071668

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Journal: Cells	Publication Date: Jul 10, 2020
Citations: 10	License type: CC BY 4.0

Affiliation: University Hospital Bonn, University of Bonn

Abstract

Background: PTEN Hamartoma Tumor Syndrome (PHTS) is caused by germline autosomal-dominant mutations of the tumor suppressor gene PTEN. Subjects harbour an increased risk for tumor development, with thyroid carcinoma occurring in young children. Establishing a diagnosis is challenging, since not all children fulfill diagnostic criteria established for adults. Macrocephaly is a common feature in childhood, with cerebral MRI being part of its diagnostic workup. We asked whether distinct cMRI features might facilitate an earlier diagnosis. Methods: We retrospectively studied radiological and clinical data of pediatric patients who were presented in our hospital between 2013 and 2019 in whom PTEN gene mutations were identified. Results: We included 27 pediatric patients (18 male) in the analysis. All patients were macrocephalic. Of these, 19 patients had received at least one cMRI scan. In 18 subjects variations were detected: enlarged perivascular spaces (EPVS; in 18), white matter abnormalities (in seven) and less frequently additional pathologies. Intellectual ability was variable. Most patients exhibited developmental delay in motor skills, but normal intelligence. Conclusion: cMRI elucidates EPVS and white matter abnormalities in a high prevalence in children with PHTS and might therefore aid as a diagnostic feature to establish an earlier diagnosis of PHTS in childhood.

Highlights

PTEN hamartoma tumor syndrome (PHTS) is caused by germline autosomal-dominant mutations of the tumor suppressor gene PTEN
Age at diagnosis of the PTEN mutation ranged from eight months to 13.5 years
Genetical analysis was performed within the diagnostic workup for a combination of macrocephaly, developmental delay and other clinical features such as penile freckling or lipoma

Summary

Introduction

PTEN hamartoma tumor syndrome (PHTS) is caused by germline autosomal-dominant mutations of the tumor suppressor gene PTEN. Juvenile polyposis of infancy, autism spectrum disorders with macrocephaly and children with macrocephaly and developmental delay and/or cognitive impairment are associated with PTEN gene mutations. Cells 2020, 9, 1668 proven PTEN mutation are at increased risk of developing benign or malignant tumors and benefit from cancer surveillance strategies. The development of thyroid carcinoma has been described in young children [2,3,4]. PTEN Hamartoma Tumor Syndrome (PHTS) is caused by germline autosomal. -dominant mutations of the tumor suppressor gene PTEN. Subjects harbour an increased risk for tumor development, with thyroid carcinoma occurring in young children. Establishing a diagnosis is challenging, since not all children fulfill diagnostic criteria established for adults. Methods: We retrospectively studied radiological and clinical data of pediatric patients who were presented in our hospital between

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