Uptake of prenatal diagnostic testing for retinoblastoma compared to other hereditary cancer syndromes in the Netherlands

Charlotte J Dommering,Arjen R Mensenkamp,Hanne Meijers-Heijboer,Lidewij Henneman,Annette C Moll,Ans M W Van Den Ouweland,Egbert J W Redeker,Frans B L Hogervorst,Carli M J Tops,Christine E M De Die-Smulders,Annemarie H Van Der Hout,Marianne A Jonker,Rob B Van Der Luijt

doi:10.1007/s10689-016-9943-z

Abstract

Since the 1980s the genetic cause of many hereditary tumor syndromes has been elucidated. As a consequence, carriers of a deleterious mutation in these genes may opt for prenatal diagnoses (PND). We studied the uptake of prenatal diagnosis for five hereditary cancer syndromes in the Netherlands. Uptake for retinoblastoma (Rb) was compared with uptake for Von Hippel–Lindau disease (VHL), Li–Fraumeni syndrome (LFS), familial adenomatous polyposis (FAP), and hereditary breast ovarian cancer (HBOC). A questionnaire was completed by all nine DNA-diagnostic laboratories assessing the number of independent mutation-positive families identified from the start of diagnostic testing until May 2013, and the number of PNDs performed for these syndromes within these families. Of 187 families with a known Rb-gene mutation, 22 had performed PND (11.8%), this was significantly higher than uptake for FAP (1.6%) and HBOC (<0.2%). For VHL (6.5%) and LFS (4.9%) the difference was not statistically significant. PND for Rb started 3 years after introduction of diagnostic DNA testing and remained stable over the years. For the other cancer syndromes PND started 10–15 years after the introduction and uptake for PND showed an increase after 2009. We conclude that uptake of PND for Rb was significantly higher than for FAP and HBOC, but not different from VHL and LFS. Early onset, high penetrance, lack of preventive surgery and perceived burden of disease may explain these differences.

Highlights

5% of all cancers are caused by a genetic predisposition, with the mode of inheritance being mainly autosomal dominant
We studied the uptake of prenatal diagnosis for five hereditary cancer syndromes in the Netherlands
We conclude that uptake of prenatal diagnoses (PND) for Rb was significantly higher than for familial adenomatous polyposis (FAP) and hereditary breast ovarian cancer (HBOC), but not different from Von Hippel–Lindau disease (VHL) and Li–Fraumeni syndrome (LFS)

Summary

Introduction

5% of all cancers are caused by a genetic predisposition, with the mode of inheritance being mainly autosomal dominant. 12 Department of Ophthalmology, VU University Medical Center, Amsterdam, The Netherlands diagnosis and management of cancer for affected mutation carriers. Prenatal diagnosis (PND) and PGD for hereditary cancer syndromes were described as early as 1988 and 1998, respectively [6, 7]. Access to PND and/or PGD is limited in some countries because they are not covered by health insurances [9] Both in society and in medical literature, PND and PGD for hereditary cancer syndromes have led to ethical, social and legal discussions [10,11,12,13,14,15]. Arguments put forward in favour of offering PND and PGD are that preventive surgery may have a large impact on psychosocial well-being [16] and that families with hereditary cancer syndromes are burdened by their increased risk and deserve the same choices as families with other high-risk hereditary diseases [12, 17]

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Conclusion