Heterogeneity in families with ATTRV30M amyloidosis: a historical and longitudinal Portuguese case study impact for genetic counselling

Abstract

Background

Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is an inherited disease, where the study of family history holds importance. This study evaluates the changes of age-of-onset (AOO) and other age-related clinical factors within and among families affected by ATTRv amyloidosis.

Methods

We analysed information from 934 trees, focusing on family, parents, probands and siblings relationships. We focused on 1494 female and 1712 male symptomatic ATTRV30M patients. Results are presented alongside a comparison of current with historical records. Clinical and genealogical indicators identify major changes.

Results

Overall, analysis of familial data shows the existence of families with both early and late patients (1/6). It identifies long familial follow-up times since patient families tend to be diagnosed over several years. Finally, results show a large difference between parent-child and proband-patient relationships (20–30 years).

Conclusions

This study reveals that there has been a shift in patient profile, with a recent increase in male elderly cases, especially regarding probands. It shows that symptomatic patients exhibit less variability towards siblings, when compared to other family members, namely the transmitting ancestors’ age of onset. This can influence genetic counselling guidelines.

Keywords:

• ATTRv amyloidosis
• epidemiological study
• genealogical data
• Portuguese families

Acknowledgements

We express our gratitude to the patients as well as the doctors and medical staff whose work made this study possible.

Ethical approval

The study was approved by the ethical and institutional review boards at Centro Hospitalar Universitário de Santo António, Porto, Portugal, prior to subject enrolment. All methods were performed in accordance with the relevant guidelines and regulations.

Disclosure statement

Teresa Coelho received support from Pfizer, Ionis, Alnylam and Biogen to attend to scientific meetings. No potential conflict of interest was reported by the author(s).

Data availability statement

Patient data is not publicly available due to restrictions e.g. ‘containing information that could compromise research participant privacy/consent’.

Additional information

Funding

This work is financed by National Funds through the Portuguese funding agency, FCT – Fundação para a Ciência e a Tecnologia, within project LA/P/0063/2020. DOI: 10.54499/LA/P/0063/2020 | https://doi.org/10.54499/LA/P/0063/2020