Genetic epidemiology of familial amyloidotic polyneuropathy (FAP)‐type I in Póvoa do Varzim and Vila do Conde (north of Portugal)

Abstract

Familial amyloidotic polyneuropathy (FAP-type I) was first described in Portugal by Andrade in 1952, a time when 54 among 64 patients (belonging to 25 families) originated from Póvoa do Varzim or its surrounding districts. Since then, a total of 1,233 patients, belonging to 489 pedigrees (so far unrelated), have been diagnosed at Centro de Estudos de Paramiloidose, Porto, Portugal. Although age-of-onset showed a wide range (17 to 78 years), 87% of these 1,233 patients developed symptoms before 40 years of age (mean 33.5, SD 9.4 years). Among all patients, 432 belong to 140 families originating from the area of Póvoa do Varzim/Vila do Conde, 330 of whom lived in that area at the time of diagnosis; age-of-onset was, on average, lower than in the overall group of patients (mean 31.1, SD 6.7 years), and no patient had onset after 57 years (versus 3.3% in the global sample). As in previous studies, women were found to have a later onset (33.7) than men (29.0) years. In 1991, the crude prevalence rate was 90.3 x 10(-5) (one in every 1,108 inhabitants), and the frequency of gene carriers was estimated to be 186 x 10(-5) (one in every 538); about 48.4% of these carriers had manifested symptoms by 1991. Female patients had a significantly higher number of children (mean 3.7, SD 2.6) than male patients (mean 2.7, SD 2.1) and the length of their reproductive period (mean 8.4, SD 5.8 yr) was also greater than for men (mean 5.6, SD 4.4 yr). Altogether, the 122 patients who ever reproduced contributed 457 children to the next generation, a mean fertility of 3.7. Further studies using a control groups may answer the question of whether this is the result of a specific high fertility of these patients or just their belonging to a population in natural expansion.

Estimating the global prevalence of transthyretin familial amyloid polyneuropathy

“…Among the 10 retained records, 8 records18, 21, 22, 23, 24, 25, 26, 27 directly reported 25 prevalence estimates pertaining to 11 countries (for pertinent details of the 10 retained records, see Table 1). National level prevalence estimates were reported for 10 of the countries, and these 10 constituted the core group of countries for which ATTR‐FAP population sizes were directly estimable.…”

Variants in RBP4 and AR genes modulate age at onset in familial amyloid polyneuropathy (FAP ATTRV30M)

“…[3][4][5][6] Among Portuguese families, a remarkable wide variation in AO (19-82 years) has been observed, and an increasing number of late-onset cases (≥50 years) are being ascertained, including asymptomatic carriers aged 95 years. 4 Variation in AO between generations has also been observed: lateonset parents often have early-onset offspring (o40 years) -an evidence for anticipation -whereas the reverse has never been observed. Recently, our group has shown that anticipation is a true biological phenomenon in FAP ATTRV30M.…”

Genotype–phenotype correlation and course of transthyretin familial amyloid polyneuropathies in France

“…Val30Met (Met30) is almost the only variant found in Portugal, where mean age at onset is 33 years, a positive family history is frequent, and penetrance is high 7, 8, 9. In Japan, Met30 families with early onset neuropathy were initially identified in 2 limited areas (Arao district and Ogawa village) with a penetrance of 80% 10.…”