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. 2024 Oct 29;19(1):403.
doi: 10.1186/s13023-024-03370-z.

Improving genetic testing pathways for transthyretin amyloidosis in France: challenges and strategies

Bérénice Hebrard  1   2   3   4 , Marie-Lise Babonneau  3 , Philippe Charron  3   5 , Emilie Consolino  3   4   6 , Benjamin Dauriat  3   7 , Delphine Dupin-Deguine  3   8 , Dominique Fargeaud  2   3   9 , Agnès Farrugia  10 , Anna-Gaëlle Giguet-Valard  11   12 , Damien Guijarro  2   13 , Jocelyn Inamo  2   11   12 , Julien Jeanneteau  2   14 , Jean-Michaël Mazzella  3   4   6 , Claire-Cécile Michon  3 , Gilles Millat  3   15 , Frédéric Mouquet  16 , Silvia Oghina  2   3   17 , Yann Pereon  12   18 , Vianney Poinsignon  12   19 , Julie Pompougnac  2   3   17 , Julie Proukhnitzky  3   5 , Elise Schaefer  3   20 , Franck Sturtz  3   21 , Mathilde Trosdorf  3 , Anne Auguste  22 , Giorgia Canali  22 , Alexandre Combes  22 , Benoît Funalot  1   2   3   23 , Thibaud Damy  24   25   26   27
Affiliations

Improving genetic testing pathways for transthyretin amyloidosis in France: challenges and strategies

Bérénice Hebrard et al. Orphanet J Rare Dis. .

Abstract

Transthyretin amyloidosis (ATTR) is a severe and rare disease characterized by the progressive deposition of misfolded transthyretin proteins, causing irreversible organ damage. Transthyretin amyloidosis can present as a hereditary ATTR or acquired wild-type ATTR form. Genetic testing is critical for determining a hereditary predisposition and subsequently initiating appropriate family screening. In France, strict regulations govern genetic testing that aim to protect patients and their families affected by hereditary diseases such as ATTR. However, challenges persist in establishing an effective genetic testing pathway. A multidisciplinary group of French experts convened to discuss the challenges associated with an ATTR genetic diagnosis and to propose improvement strategies. Key challenges include the lack of pathway standardization, communication gaps between healthcare professionals (HCPs) and patients, and difficulties in complying with regulatory requirements. Concerns about patient data safety and outsourced testing quality further complicate matters. Proposed strategies included the development of stakeholder mapping tools for HCPs and patients, educational programs to improve literacy on genetic testing regulations, increase disease awareness among medical geneticists and genetic counselors, and strengthening HCP-patient communication through educational materials. These initiatives aim to streamline the genetic testing pathway, enhance compliance with regulations, and ultimately provide optimal support for patients and families with ATTR.

Keywords: ATTR; Experts’ consensus; Genetic testing; Multidisciplinary expert group; Rare disease.

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Conflict of interest statement

BD, BF, BH, DG, EC, ES, FM, JPo, SO, TD and YP have received honoraria from Pfizer related to this work. BD has received honoraria from Pfizer. ES has received honoraria from Alnylam and Pfizer. FM has received honoraria from BMS and Pfizer. PC has received honoraria from Amicus, BMS, Owkin, Pfizer and Sanofi. SO has received honoraria from Pfizer. TD has received honoraria from Alexion, Alnylam, Akcea, Bridge Bio, Ionis, Neurimmune, Novo Nordisk and Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

Fig. 1
Fig. 1
Genetic Pathways for patients with suspected or proven clinical ATTR
Fig. 2
Fig. 2
Genetic Pathways for asymptomatic relatives. 1. According to French legislation defining best practices for genetic testing [15]; 2. Defined by the French Public Health Legislation [11]; 3. Defined by the French Civil Code [16]; 4. Filière CARDIOGEN, Centre de référence Amyloses Cardiaques, rotocole National de Diagnostic et de Soins (PNDS) Amyloses Cardiaque (2020–2021); 5. Centre de Référence des Neuropathies Amyloïdes Familiales et Autres Neuropathies Périphériques Rares (NNERf), Protocole National de Diagnostic et de Soins (PNDS) Neuropathie amyloïde familiale
Fig. 3
Fig. 3
Principles and main stakeholders involved for the mapping of laboratories offering TTR analysis, clinical genetic services and amyloidosis experts
See this image and copyright information in PMC

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Supplementary concepts