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SCA2 predictive testing in Cuba: challenging concepts and protocol evolution

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Abstract

Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease caused by a CAG repeat expansion in the ATXN2 gene. Cuba has the highest prevalence (6.57 cases/105 inhabitants) of SCA2 in the world. The existence of 753 affected individuals and 7173 relatives at risk prompted the development in 2001 of the first predictive testing program in the country. The medical records of over 1193 individuals, who requested the test within a 13-year period, were analyzed retrospectively. The presymptomatic and the prenatal tests had uptake rates of 43.4 and 23.9 %, respectively. Several ethical challenges resulted from this program. These include the following: (1) withdrawal due to the initial protocol’s length; (2) the request to participate by 16 at-risk adolescents; (3) the decision made by ten out of 33 couples with a test-positive fetus to carry the pregnancy to term, leading to de facto predictive testing of minors; (4) the elevated frequency of the ATXN2 gene large normal alleles (≥23 to 31 repeats) in the reference population. These issues have led to major changes in the guidelines of the predictive testing protocol: (1) the protocol length was shortened; (2) the inclusion criteria were expanded to reach at-risk adolescents with an interest in prenatal diagnosis; (3) interdisciplinary follow-up was offered to families in which test-positive fetuses were not aborted; (4) prenatal testing was made available to carriers of large normal alleles with ≥27 CAG repeats. The profiles of the participants were similar to those reported for other predictive testing programs for conditions like Huntington disease and familial adenomatous polyposis. The genetic counseling practices at the community level, the ample health education provided to the at-risk population, together with multidisciplinary and specialized attention to the affected families, are lessons from the Cuban experience that can be relevant for other international teams conducting predictive testing for other late-onset neurodegenerative disorders.

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Acknowledgments

The authors are deeply indebted to the SCA2 Cuban families and to the Cuban Ministry of Health. We would like to praise the work of BSc Nieves Santos Falcón, MD Karell Escalona Batallán, MD Humberto Jorge Cedeño, MD Ruben Reynaldo Armiñan, MD Mercedes Velázquez, BSc Nalia Canales Ochoa, BSc Arnoy Peña Acosta, BSc Roberto Rodríguez Labrada, and BSc Rafael Bestard. We are thankful to José Luis Guisao Martínez for the language corrections and to MD Patrick MacLeod for his contribution to the program along these years.

Compliance with ethical guidelines

The presymptomatic testing and the prenatal diagnosis procedures are in compliance with the laws existing in Cuba. They are in accordance with the ethical standards of CIRAH and with the Helsinki declaration of 1975 as revised in 2000. All participants were informed about PST and PND procedures and protocol, as well as the possibility of using information from their clinical records in clinical research and they gave their separate written consent for both.

Conflict of interest

Authors declare no conflicts of interest

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    Authors and Affiliations

    1. Predictive Genetics Department, Center for the Research and Rehabilitation of Hereditary Ataxias, Holguín, Cuba

      Tania Cruz-Mariño & Miguel Velázquez-Santos

    2. Molecular Neurobiology Department, Center for the Research and Rehabilitation of Hereditary Ataxias, Holguín, Cuba

      Yaimeé Vázquez-Mojena, Yanetza González-Zaldívar, José Miguel Laffita-Mesa & Luis E. Almaguer-Mederos

    3. Neurophysiology Department, Center for the Research and Rehabilitation of Hereditary Ataxias, Libertad Street 26, Holguín, Cuba, 80100

      Luis Velázquez-Pérez

    4. Clinical Department, Center for the Research and Rehabilitation of Hereditary Ataxias, Holguín, Cuba

      Raúl Aguilera-Rodríguez & Annelié Estupiñán-Rodríguez

    5. Center for Predictive and Preventive Genetics IBMC-Institute for Molecular and Cell Biology, University of Porto, Porto, Portugal

      Milena Paneque

    6. Calle 4 de Abril #6, Entre Final y Carretera de Gibara, Reparto Luz, Holguín, Cuba, 80100

      Tania Cruz-Mariño

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    1. Tania Cruz-Mariño
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    Corresponding authors

    Correspondence to Tania Cruz-Mariño or Luis Velázquez-Pérez.

    Additional information

    This article is part of the special issue on “Genetics and Ethics in Latin America.”

    Tania Cruz-Mariño and Yaimeé Vázquez-Mojena contributed equally to this work.

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    Cruz-Mariño, T., Vázquez-Mojena, Y., Velázquez-Pérez, L. et al. SCA2 predictive testing in Cuba: challenging concepts and protocol evolution. J Community Genet 6, 265–273 (2015). https://doi.org/10.1007/s12687-015-0226-4

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    • DOI: https://doi.org/10.1007/s12687-015-0226-4

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