The benefits and challenges of family genetic testing in rare genetic diseases—lessons from Fabry disease

Mol Genet Genomic Med. 2021 Apr 9;e1666. doi: 10.1002/mgg3.1666. Online ahead of print.

PMID: 33835733

Dominique P. Germain | Sergey Moiseev | Fernando Suárez-Obando | Faisal Al Ismaili | Huda Al Khawaja | Gheona Altarescu | Fellype C. Barreto | Farid Haddoum | Fatemeh Hadipour | Irina Maksimova | Mirelle Kramis | Sheela Nampoothiri | Khanh Ngoc Nguyen | Dau-Ming Niu | Juan Politei | Long-Sun Ro | Dung Vu Chi | Nan Chen | Sergey Kutsev

Summary: In this review, the problems faced in the family genetic screening of patients affected with rare genetic diseases are highlighted by an international group of experts of Fabry disease. These problems include related costs, low awareness of its importance, cultural and societal issues, educational levels of the population, national geography and infrastructure, and a lack of medical geneticists.

Abstract

Background: When a patient is newly diagnosed with a rare genetic disorder, family genetic testing may help with early identification of family members, enabling patients to undergo disease-specific treatments as soon as possible. Fabry disease, an X-linked storage disorder, can lead to end-stage renal disease, cardiac arrhythmias, and stroke. Due to the disease rarity and the non-specific early symptoms, diagnostic delays are common. Individuals with Fabry disease can be identified by newborn screening and screening of high-risk populations (e.g., patients with hypertrophic cardiomyopathy or undiagnosed nephropathies). A greater number of affected individuals may be identified with subsequent cascade genotyping of family members, often at younger age than they would have been diagnosed otherwise.

Methods: Literature search was conducted to identify all published data on family genetic testing for Fabry disease and these data were discussed, as well as experts' personal experiences with family genetic testing and the obstacles to this screening in their countries.

Results: In some countries, there are possible obstacles that make family genetic screening difficult to implement. These include related costs and low awareness of its importance, and cultural and societal issues. Regionally, obstacles include educational levels of the population, national geography and infrastructure, and a lack of medical geneticists.

Conclusion: In this review, the problems faced in the family genetic screening of patients affected with rare genetic diseases are highlighted by an international group of experts of Fabry disease.