Meeting patients’ right to the correct diagnosis: Ongoing international initiatives on undiagnosed rare diseases and ethical and social issues

Sabina Gainotti, Deborah Mascalzoni, Virginie Bros-Facer, Carlo Petrini, Giovanna Floridia, Marco Roos, Marco Salvatore, Domenica Taruscio

Research output: Contribution to journalReview article

3 Citations (Scopus)

Abstract

The time required to reach a correct diagnosis is a key concern for rare disease (RD) patients. Diagnostic delay can be intolerably long, often described as an “odyssey” and, for some, a diagnosis may remain frustratingly elusive. The International Rare Disease Research Consortium proposed, as ultimate goal for 2017–2027, to enable all people with a suspected RD to be diagnosed within one year of presentation, if the disorder is known. Subsequently, unsolved cases would enter a globally coordinated diagnostic and research pipeline. In-depth analysis of the genotype through next generation sequencing, together with a standardized in-depth phenotype description and sophisticated high-throughput approaches, have been applied as diagnostic tools to increase the chance of a timely and accurate diagnosis. The success of this approach is evident in the Orphanet database. From 2010 to March 2017 over 600 new RDs and roughly 3600 linked genes have been described and identified. However, combination of-omics and phenotype data, as well as international sharing of this information, has raised ethical concerns. Values to be assessed include not only patient autonomy but also family implications, beneficence, non-maleficence, justice, solidarity and reciprocity, which must be respected and promoted and, at the same time, balanced among each other. In this work we suggest that, to maximize patients’ involvement in the search for a diagnosis and identification of new causative genes, undiagnosed patients should have the possibility to: (1) actively participate in the description of their phenotype; (2) choose the level of visibility of their profile in matchmaking databases; (3) express their preferences regarding return of new findings, in particular which level of Variant of Unknown Significance (VUS) significance should be considered relevant to them. The quality of the relationship between individual patients and physicians, and between the patient community and the scientific community, is critically important for optimizing the use of available data and enabling international collaboration in order to provide a diagnosis, and the attached support, to unsolved cases. The contribution of patients to collecting and coding data comprehensively is critical for efficient use of data downstream of data collection.

Original languageEnglish
Article number2072
JournalInternational Journal of Environmental Research and Public Health
Volume15
Issue number10
DOIs
Publication statusPublished - Oct 1 2018

Fingerprint

Patient Rights
Rare Diseases
Ethics
Phenotype
Databases
Beneficence
Patient Participation
Information Dissemination
Social Justice
Research
Genes
Genotype
Physicians

Keywords

  • Deep phenotyping
  • Diagnostic odyssey
  • Genomic matchmaking
  • Next generation sequencing
  • Patient involvement
  • Secondary findings
  • Undiagnosed rare diseases

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Cite this

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title = "Meeting patients’ right to the correct diagnosis: Ongoing international initiatives on undiagnosed rare diseases and ethical and social issues",
abstract = "The time required to reach a correct diagnosis is a key concern for rare disease (RD) patients. Diagnostic delay can be intolerably long, often described as an “odyssey” and, for some, a diagnosis may remain frustratingly elusive. The International Rare Disease Research Consortium proposed, as ultimate goal for 2017–2027, to enable all people with a suspected RD to be diagnosed within one year of presentation, if the disorder is known. Subsequently, unsolved cases would enter a globally coordinated diagnostic and research pipeline. In-depth analysis of the genotype through next generation sequencing, together with a standardized in-depth phenotype description and sophisticated high-throughput approaches, have been applied as diagnostic tools to increase the chance of a timely and accurate diagnosis. The success of this approach is evident in the Orphanet database. From 2010 to March 2017 over 600 new RDs and roughly 3600 linked genes have been described and identified. However, combination of-omics and phenotype data, as well as international sharing of this information, has raised ethical concerns. Values to be assessed include not only patient autonomy but also family implications, beneficence, non-maleficence, justice, solidarity and reciprocity, which must be respected and promoted and, at the same time, balanced among each other. In this work we suggest that, to maximize patients’ involvement in the search for a diagnosis and identification of new causative genes, undiagnosed patients should have the possibility to: (1) actively participate in the description of their phenotype; (2) choose the level of visibility of their profile in matchmaking databases; (3) express their preferences regarding return of new findings, in particular which level of Variant of Unknown Significance (VUS) significance should be considered relevant to them. The quality of the relationship between individual patients and physicians, and between the patient community and the scientific community, is critically important for optimizing the use of available data and enabling international collaboration in order to provide a diagnosis, and the attached support, to unsolved cases. The contribution of patients to collecting and coding data comprehensively is critical for efficient use of data downstream of data collection.",
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author = "Sabina Gainotti and Deborah Mascalzoni and Virginie Bros-Facer and Carlo Petrini and Giovanna Floridia and Marco Roos and Marco Salvatore and Domenica Taruscio",
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AU - Mascalzoni, Deborah

AU - Bros-Facer, Virginie

AU - Petrini, Carlo

AU - Floridia, Giovanna

AU - Roos, Marco

AU - Salvatore, Marco

AU - Taruscio, Domenica

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