• Violaine Planté-Bordeneuve, Farida Gorram, Malin Olsson, Intissar Anan, Anna Mazzeo, Luca Gentile, Eugenia Cisneros-Barroso, Juan Gonzalez-Moreno, Ines Losada, Marcia Waddington-Cruz, Luiz Felipe Pinto, Yeşim Parman, Pascale Fanen, Flora Alarcon, and Gregory Nuel.
• Department of Neurology, Henri Mondor University Hospital, APHP, Créteil, France.
• Amyloid. 2023 Sep 1; 30 (3): 313320313-320.

BackgroundIn hereditary transthyretin amyloidosis (ATTRv), early manifestation and age at onset (AO) may vary strikingly. We assessed the disease'risk (penetrance), AO and initial features in ATTRv families to gain insights on the early disease presentation.MethodsGenealogical information, AO and first disease manifestations were collected in ATTRv families, from Sweden, Italy (Sicily), Spain (Mallorca), France, Turkey, Brazil. Penetrance was computed using a non-parametric survival method.ResultsWe analysed 258 TTRV30M kindreds and 84 carrying six other variants (TTRT49A, F64L, S77Y, S77F, E89Q, I107V). In ATTRV30M families, the earliest disease risk was found at age 20 years in the Portuguese and Mallorcan families and at age 30-35 years, in the French and Swedish groups. The risks were higher in men and in carriers of maternal descent. In families carrying TTR-nonV30M variants, the earliest disease risk ranged from 30 y-o in TTRT49A to 55 y-o in TTRI107V families. Peripheral neuropathy symptoms were the most frequent initial manifestations. Among patients carrying TTRnonV30M variants, about 25% had an initial cardiac phenotype, one third a mixed phenotype.ConclusionOur work provided solid data on the risks and early features of ATTRv in a spectrum of families to enhance an early diagnosis and treatment.

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