Recommendations for pre-symptomatic genetic testing for hereditary transthyretin amyloidosis in the era of effective therapy: a multicenter Italian consensus
Abstract Hereditary transthyretin amyloidosis (ATTRv, v for variant) is a late-onset, autosomal dominant disease caused by progressive extracellular deposition of transthyretin amyloid fibrils, leading to organ damage and death. For other late-onset fatal diseases, as Huntington’s disease, protocols...
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BMC
2020-12-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-020-01633-z |
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| author | M. Grandis L. Obici M. Luigetti C. Briani F. Benedicenti G. Bisogni M. Canepa F. Cappelli C. Danesino G. M. Fabrizi S. Fenu G. Ferrandes C. Gemelli F. Manganelli A. Mazzeo L. Melchiorri F. Perfetto L. G. Pradotto P. Rimessi G. Tini S. Tozza L. Trevisan D. Pareyson P. Mandich |
| author_facet | M. Grandis L. Obici M. Luigetti C. Briani F. Benedicenti G. Bisogni M. Canepa F. Cappelli C. Danesino G. M. Fabrizi S. Fenu G. Ferrandes C. Gemelli F. Manganelli A. Mazzeo L. Melchiorri F. Perfetto L. G. Pradotto P. Rimessi G. Tini S. Tozza L. Trevisan D. Pareyson P. Mandich |
| author_sort | M. Grandis |
| collection | DOAJ |
| description | Abstract Hereditary transthyretin amyloidosis (ATTRv, v for variant) is a late-onset, autosomal dominant disease caused by progressive extracellular deposition of transthyretin amyloid fibrils, leading to organ damage and death. For other late-onset fatal diseases, as Huntington’s disease, protocols for pre-symptomatic genetic testing (PST) are available since decades. For ATTRv, limited experience has been reported to date, mostly gathered before the availability of approved therapies. We aimed at developing recommendations for a safe and feasible PST protocol in ATTRv in the era of emerging treatments, taking also into account Italian patients’ characteristics and healthcare system rules. After an initial survey on ongoing approaches to PST for ATTRv in Italy, two roundtable meetings were attended by 24 experts from 16 Italian centers involved in the diagnosis and care of this disease. Minimal requirements for PST offer and potential critical issues were highlighted. By November 2019, 457 families affected by ATTRv with 209 molecularly confirmed pre-symptomatic carriers were counted. The median age at PST was 41.3 years of age, regardless of the specific mutation. Half of the Italian centers had a multidisciplinary team, including a neurologist, an internist, a cardiologist, a medical geneticist and a psychologist, although in most cases not all the specialists were available in the same center. A variable number of visits was performed at each site. Experts agreed that PST should be offered only in the context of genetic counselling to at risk individuals aged 18 or older. Advertised commercial options for DNA testing should be avoided. The protocol should consist of several steps, including a preliminary clinical examination, a pre-test information session, an interval time, the genetic test and a post-test session with the disclosure of the test results, in the context of an experienced multidisciplinary team. Recommendations for best timing were also defined. Protocols for PST in the context of ATTRv can be refined to offer at risk individuals the best chance for early diagnosis and timely treatment start, while respecting autonomous decisions and promoting safe psychological adjustment to the genetic result. |
| first_indexed | 2024-12-21T14:17:33Z |
| format | Article |
| id | doaj.art-06f1cac9f11446abaa06ec95182536f4 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-21T14:17:33Z |
| publishDate | 2020-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-06f1cac9f11446abaa06ec95182536f42022-12-21T19:00:51ZengBMCOrphanet Journal of Rare Diseases1750-11722020-12-011511710.1186/s13023-020-01633-zRecommendations for pre-symptomatic genetic testing for hereditary transthyretin amyloidosis in the era of effective therapy: a multicenter Italian consensusM. Grandis0L. Obici1M. Luigetti2C. Briani3F. Benedicenti4G. Bisogni5M. Canepa6F. Cappelli7C. Danesino8G. M. Fabrizi9S. Fenu10G. Ferrandes11C. Gemelli12F. Manganelli13A. Mazzeo14L. Melchiorri15F. Perfetto16L. G. Pradotto17P. Rimessi18G. Tini19S. Tozza20L. Trevisan21D. Pareyson22P. Mandich23Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), Section of Medical Genetics, University of GenoaAmyloidosis Research and Treatment Center, IRCCS Fondazione Policlinico San MatteoUOC Neurologia, Fondazione Policlinico Universitario A. Gemelli IRCCSDepartment of Neuroscience, University of PadovaMedical Genetics, Azienda Sanitaria Dell’Alto AdigeCentro Clinico Nemo Adulti-Fondazione Policlinico Universitario Agostino Gemelli IRCCSCardiovascular Disease Unit, IRCCS Policlinico San Martino, Genova, and IRCCS Italian Cardiovascular Network, Department of Internal Medicine, University of GenovaTuscan Regional Amyloidosis Center, Careggi University HospitalMolecular Medicine Department, University of PaviaDepartment of Neurosciences, Biomedicine and Movement Sciences, Section of Neurology, University of Verona and University Hospital GB RossiUnit of Rare Neurodegenerative and Neurometabolic Diseases, Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo BestaIRCCS Policlinico San MartinoDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), Section of Medical Genetics, University of GenoaDepartment of Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples “Federico II”Unit of Neurology and Neuromuscular Diseases, Department of Clinical and Experimental Medicine, University of MessinaMedical Genetics Unit, Azienda Ospedaliero Universitaria Di FerraraTuscan Regional Amyloidosis Center, Careggi University HospitalDepartment of Neurosciences, University of TurinMedical Genetics Unit, Azienda Ospedaliero Universitaria Di FerraraCardiovascular Disease Unit, IRCCS Policlinico San Martino, Genova, and IRCCS Italian Cardiovascular Network, Department of Internal Medicine, University of GenovaDepartment of Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples “Federico II”Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), Section of Medical Genetics, University of GenoaUnit of Rare Neurodegenerative and Neurometabolic Diseases, Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo BestaDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), Section of Medical Genetics, University of GenoaAbstract Hereditary transthyretin amyloidosis (ATTRv, v for variant) is a late-onset, autosomal dominant disease caused by progressive extracellular deposition of transthyretin amyloid fibrils, leading to organ damage and death. For other late-onset fatal diseases, as Huntington’s disease, protocols for pre-symptomatic genetic testing (PST) are available since decades. For ATTRv, limited experience has been reported to date, mostly gathered before the availability of approved therapies. We aimed at developing recommendations for a safe and feasible PST protocol in ATTRv in the era of emerging treatments, taking also into account Italian patients’ characteristics and healthcare system rules. After an initial survey on ongoing approaches to PST for ATTRv in Italy, two roundtable meetings were attended by 24 experts from 16 Italian centers involved in the diagnosis and care of this disease. Minimal requirements for PST offer and potential critical issues were highlighted. By November 2019, 457 families affected by ATTRv with 209 molecularly confirmed pre-symptomatic carriers were counted. The median age at PST was 41.3 years of age, regardless of the specific mutation. Half of the Italian centers had a multidisciplinary team, including a neurologist, an internist, a cardiologist, a medical geneticist and a psychologist, although in most cases not all the specialists were available in the same center. A variable number of visits was performed at each site. Experts agreed that PST should be offered only in the context of genetic counselling to at risk individuals aged 18 or older. Advertised commercial options for DNA testing should be avoided. The protocol should consist of several steps, including a preliminary clinical examination, a pre-test information session, an interval time, the genetic test and a post-test session with the disclosure of the test results, in the context of an experienced multidisciplinary team. Recommendations for best timing were also defined. Protocols for PST in the context of ATTRv can be refined to offer at risk individuals the best chance for early diagnosis and timely treatment start, while respecting autonomous decisions and promoting safe psychological adjustment to the genetic result.https://doi.org/10.1186/s13023-020-01633-zAttrvHereditary transthyretin amyloidosisPre-symptomatic genetic testing; PST |
| spellingShingle | M. Grandis L. Obici M. Luigetti C. Briani F. Benedicenti G. Bisogni M. Canepa F. Cappelli C. Danesino G. M. Fabrizi S. Fenu G. Ferrandes C. Gemelli F. Manganelli A. Mazzeo L. Melchiorri F. Perfetto L. G. Pradotto P. Rimessi G. Tini S. Tozza L. Trevisan D. Pareyson P. Mandich Recommendations for pre-symptomatic genetic testing for hereditary transthyretin amyloidosis in the era of effective therapy: a multicenter Italian consensus Orphanet Journal of Rare Diseases Attrv Hereditary transthyretin amyloidosis Pre-symptomatic genetic testing; PST |
| title | Recommendations for pre-symptomatic genetic testing for hereditary transthyretin amyloidosis in the era of effective therapy: a multicenter Italian consensus |
| title_full | Recommendations for pre-symptomatic genetic testing for hereditary transthyretin amyloidosis in the era of effective therapy: a multicenter Italian consensus |
| title_fullStr | Recommendations for pre-symptomatic genetic testing for hereditary transthyretin amyloidosis in the era of effective therapy: a multicenter Italian consensus |
| title_full_unstemmed | Recommendations for pre-symptomatic genetic testing for hereditary transthyretin amyloidosis in the era of effective therapy: a multicenter Italian consensus |
| title_short | Recommendations for pre-symptomatic genetic testing for hereditary transthyretin amyloidosis in the era of effective therapy: a multicenter Italian consensus |
| title_sort | recommendations for pre symptomatic genetic testing for hereditary transthyretin amyloidosis in the era of effective therapy a multicenter italian consensus |
| topic | Attrv Hereditary transthyretin amyloidosis Pre-symptomatic genetic testing; PST |
| url | https://doi.org/10.1186/s13023-020-01633-z |
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