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Meta-Analysis
. 2018 Mar;176(3):597-608.
doi: 10.1002/ajmg.a.38603. Epub 2018 Jan 23.

Benign and malignant tumors in Rubinstein-Taybi syndrome

Max V Boot  1 , Martine J van Belzen  2 , Lucy I Overbeek  3 , Nathalie Hijmering  1 , Matias Mendeville  1 , Quinten Waisfisz  4 , Pieter Wesseling  1   5 , Raoul C Hennekam  6 , Daphne de Jong  1
Affiliations
Meta-Analysis

Benign and malignant tumors in Rubinstein-Taybi syndrome

Max V Boot et al. Am J Med Genet A. 2018 Mar.

Abstract

Rubinstein-Taybi syndrome (RSTS) is a multiple congenital anomalies syndrome associated with mutations in CREBBP (70%) and EP300 (5-10%). Previous reports have suggested an increased incidence of specific benign and possibly also malignant tumors. We identified all known individuals diagnosed with RSTS in the Netherlands until 2015 (n = 87) and studied the incidence and character of neoplastic tumors in relation to their CREBBP/EP300 alterations. The population-based Dutch RSTS data are compared to similar data of the Dutch general population and to an overview of case reports and series of all RSTS individuals with tumors reported in the literature to date. Using the Nationwide Network and Registry of Histopathology and Cytopathology in the Netherlands (PALGA Foundation), 35 benign and malignant tumors were observed in 26/87 individuals. Meningiomas and pilomatricomas were the most frequent benign tumors and their incidence was significantly elevated in comparison to the general Dutch population. Five malignant tumors were observed in four persons with RSTS (medulloblastoma; diffuse large-cell B-cell lymphoma; breast cancer; non-small cell lung carcinoma; colon carcinoma). No clear genotype-phenotype correlation became evident. The Dutch population-based data and reported case studies underscore the increased incidence of meningiomas and pilomatricomas in individuals with RSTS. There is no supporting evidence for an increased risk for malignant tumors in individuals with RSTS, however, due to the small numbers this risk may not be fully dismissed.

Keywords: CREBBP; EP300; Rubinstein-Taybi syndrome; diffuse large B-cell lymphoma; meningioma; neoplasia.

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Figures

Figure 1
Figure 1
Cumulative incidence of malignant tumors and meningiomas in Dutch individuals with molecularly confirmed RSTS compared to that of the general Dutch population per age cohort. Blue, malignant tumors in the general Dutch population; green, malignant tumors in the Dutch RSTS population; orange, meningiomas in the Dutch RSTS population (Cumulative meningioma incidence is <0,1% in general Dutch population). Data on general population from www.cijfersoverkanker.nl (retrieved June, 2017). [Color figure can be viewed at wileyonlinelibrary.com]
Figure 2
Figure 2
Variants in CREBBP in present cohort of individuals with RSTS with pilomatricoma, meningioma, intracranial malignancies, and other malignancies, compared to all CREBBP variants reported in LOVD. Various functional protein domains are indicated schematically. Individuals with a tumor from the present series of individuals with RSTS are indicated above the protein cartoon, individuals with RSTS reported in the LOVD are reported below the cartoon, each line or symbol representing a single individual. No specific distinction can be made between those with and without tumors in the latter series as this information is not known for all individuals. [Color figure can be viewed at wileyonlinelibrary.com]
See this image and copyright information in PMC

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