[No Title Available]

Abstract

Machado-Joseph disease (MJD) is an autosomal dominant, late-onset neurological disorder and the most common form of spinocerebellar ataxia (SCA) worldwide. Diagnostic genetic testing is available to detect the disease-causing mutation by direct sizing of the CAG repeat tract in the ataxin 3 gene. Presymptomatic testing (PST) can be used to identify persons at risk of developing the disease. Genetic counseling provides patients with information about the disease, genetic risks, PST, and the decision-making process. In this study, we present the protocol used in PST for MJD and the relevant observations from two centers: Brazil (Porto Alegre) and Portugal (Porto). We provide a case report that illustrates the significant ethical and psychological issues related to PST in late-onset neurological disorders. In both centers, counseling and PST are performed by a multidisciplinary team, and genetic testing is conducted at the same institutions. From 1999 to 2012, 343 individuals sought PST in Porto Alegre; 263 (77%) of these individuals were from families with MJD. In Porto, 1,530 individuals sought PST between 1996 and 2013, but only 66 (4%) individuals were from families with MJD. In Brazil, approximately 50% of the people seeking PST eventually took the test and received their results, whereas 77% took the test in Portugal. In this case report, we highlight several issues that might be raised by the consultand and how the team can extract significant information. Literature about PST testing for MJD and other SCAs is scarce, and we hope this report will encourage similar studies and enable the implementation of PST protocols in other populations, mainly in Latin America.

Computational neurobiology is a useful tool in translational neurology: the example of ataxia

“…SCA modeling would therefore be integrated with genomic testing, family history considerations, and presymptomatic investigation and treatment. Presymptomatic testing is often pursued for severe late-onset neurodegenerative diseases, including SCAs (Guimarães et al, 2013 ; Schuler-Faccini et al, 2014 ). Even without genetic testing, other early clinical disease features (prodromes) are detectable prior to onset of ataxia and can be used to determine treatment timing (Velázquez-Pérez et al, 2014a , b ).…”

Genetic counseling and testing practices for late-onset neurodegenerative disease: a systematic review

“…Where symptoms were identified as part of the neurological or psychiatric/psychological assessment, the response varied. Many teams proceeded with predictive testing if clients perceived themselves as asymptomatic [ 28 , 30 , 41 , 43 , 44 , 46 , 57 ], while others excluded symptomatic individuals from their predictive testing protocol [ 45 , 57 ]. In the one study that discussed neurological and psychological assessments in reproductive testing, a couple’s request for IVF could be rejected if symptoms were present in a parent and the couple seemed unable to provide a stable home environment [ 58 ].…”

“…Others were concerned that the psychological assessments pre-testing were unnecessary or that testing would be withheld based on the clients’ psychological state [ 33 , 41 , 43 , 47 ]. Consequently, fourteen papers suggested predictive testing be conducted in a more individual, flexible way by adapting the protocol to the specific needs, information processed and decision-making of the client [ 39 , 40 , 42 , 44 , 46 – 50 , 57 , 59 , 61 – 63 ]. Adaptations included reducing the number of appointments [ 46 , 48 , 57 , 59 , 63 ], tailoring the content [ 46 – 48 , 59 , 63 ] or adapting the psychological support provided to each individual’s needs [ 46 , 50 ].…”

Population medical genetics: translating science to the community

“…The search for a modifier treatment for this autosomal dominant disease did not prevent us to focus on genetic counseling and on pre-symptomatic testing as primary prevention tools not only for familial planning, but also for reducing anxiety related to uncertainty. Decision making process on pre-symptomatic testing was the subject of two studies by our group (Rodrigues et al , 2012; Schuler-Faccini et al , 2014).…”