Hereditary Transthyretin Amyloidosis: Opportunities & Challenges

Abstract

Hereditary transthyretin amyloidosis (hATTR) is a progressive, autosomal dominant, multisystem disease with incomplete and age-related penetrance. The disease presents many challenges for diagnosis, as well as presymptomatic and symptomatic management, due to its clinical heterogeneity. With the recent approval of three therapeutics by the Food and Drug Administration (FDA), the medical community has become increasingly aware of hATTR. Despite this increase in awareness, hATTR is still underdiagnosed. With the aim of raising awareness of this condition among a variety of healthcare providers, clinical information was extracted from over 400 original research articles in order to create an updated variant tabulation. With now over 130 pathogenic TTR variants, and a total of greater than 150 variants, an updated variant tabulation is necessary. Clinical manifestations and ages of onset were of particular interest and variants with the most severe phenotype are described in further detail. Finally, an analysis of genetic counseling issues is conducted, utilizing updated knowledge of the condition to provide a thorough examination of genetic counseling challenges specific to hATTR amyloidosis.