Cascade carrier testing after a child is diagnosed with cystic fibrosis through newborn screening: investigating why most relatives do not have testing

Abstract

Original research article INTRODUCTIONNewborn screening (NBS) for cystic fibrosis (CF) has increasingly been adopted by many countries worldwide, including Australia and New Zealand (since 1981), the United Kingdom (2007), a number of other countries and regions in Europe, and the United States. [1][2][3] The birth prevalence of CF is ~1 in 3,500 for northern European populations, 4 with a carrier frequency of 1 in 25, making it the most common severe recessive condition in children. In the state of Victoria, Australia, CF has been part of NBS since 1989, using immunoreactive trypsinogen as the screening analyte, and from 1991, using CF transmembrane conductance regulator gene mutation analysis for elevated immunoreactive trypsinogen results. 5A supplement edition of Genetics in Medicine (December 2010) highlighted the need for establishing systems for shortand longer-term follow-up of children who receive positive screening results from NBS. Long-term follow-up of children diagnosed with CF is generally achievable due to their ongoing treatment and management. 6 One important area that has been poorly studied is the impact of family cascade testing following a child's diagnosis of CF through NBS. "Cascade testing" is the term often used to describe genetic testing of relatives of a person diagnosed with a genetic condition or identified as a genetic carrier. The "cascade" refers to the process of testing an individual for the familial mutation(s) and then, in the event of a positive result, descendants are tested; descendants of an individual who receives a negative result are not tested. The diagnosis of a child with CF inherently means relatives are at increased risk of being CF carriers (e.g., aunts and uncles of a child with CF have a 50% risk). Carrier relatives may have their partners tested. When both partners are identified to be carriers, knowledge of carrier status provides relatives with information that may be used to make reproductive decisions, which might include having no (more) children, prenatal diagnosis, preimplantation genetic diagnosis, using donor gametes, and adoption.We have previously investigated cascade carrier testing of relatives of children diagnosed with CF through NBS in Victoria, Australia. Parents are counseled regarding the familial implications at the time of their child's diagnosis and are provided with a letter to give to relatives to assist them with communicating the genetic information.7 Even though carrier testing was free of charge to relatives who wished to receive testing, only 11.8% of relatives accessed carrier testing. 8 The aim of this study was to explore the reasons why relatives access or do not access carrier testing following a child's diagnosis of CF by NBS.Purpose: Newborn screening for cystic fibrosis is increasingly available, but cascade testing following the diagnosis in a child has received little attention. We previously reported low levels of cascade testing over time, and this study investigated motivators as well as barriers to testing. Methods:P...

Improving family communication after a new genetic diagnosis: a randomised controlled trial of a genetic counselling intervention

“…Further, while probands frequently describe feeling a sense of obligation about informing other at-risk relatives [7], they may be reluctant to do so due to existing challenging family dynamics and relationships [8,9]. Finally, probands may wish to protect their family members from anxiety [10-13] or they may be experiencing difficulties in coming to terms with their own diagnosis, [1,14] making communication problematic.…”

Highlighting the impact of cascade carrier testing in cystic fibrosis families

“…Investigating the reasons for not testing in relatives of 30 CF children diagnosed through newborn screening, McClaren et al [33] recently showed that the main reasons mentioned by relatives are irrelevant perception of the test's usefulness, lack of awareness of the possibility to do the test and test considered as something to do later.…”

“…Communication should certainly be easier since set up of NBS programs and multidisciplinary disease management in CF centers. The need to provide support to parents to facilitate the information transmission appears crucial [33]. Recent changes in French laws that now allow GPs to inform relatives of CF patients might have an impact on the uptake rate of testing in the coming years.…”

Epithelial ovarian cancer risk: A review of the current genetic landscape

“…The reasons for this are likely multifactorial, including insufficient referrals to clinical genetics, variable reporting of relatives by probands, inadequate understanding and communication of tests, feelings of irrelevance and deferring the process by relatives. [100][101][102] The use of screening has been investigated. The risk of ovarian cancer algorithm (ROCA) using serum CA125 and transvaginal ultrasound has been proposed for high-risk women; however, impact on survival is not known.…”

“…Uptake of cascade testing in this situation has been noted to be relatively low, estimated at 15% to 57% in one systematic review and genetic testing in eligible women with ovarian cancer also low. The reasons for this are likely multifactorial, including insufficient referrals to clinical genetics, variable reporting of relatives by probands, inadequate understanding and communication of tests, feelings of irrelevance and deferring the process by relatives . The use of screening has been investigated.…”