Discordant penetrance of the trait for familial amyloidotic polyneuropathy in two pairs of monozygotic twins

Abstract

Background: Familial amyloidotic polyneuropathy (FAP) is caused by mutated transthyretin in which valine at position 30 is substituted by methionine (ATTR Val30Met). FAP is inherited as an autosomal dominant trait with variable penetrance.

Cases: Two pairs of DNA confirmed monozygotic twin brothers, 63 and 37 years of age respectively, who are heterozygous for the ATTR Val30Met gene, have been identified in Sweden. In the first twin pair (A), the onset of typical FAP symptoms occurred at the age of 48 for twin A1, whilst his twin brother (A2) is still free from FAP symptoms 13 years later. In the second pair of twins (B), the onset of polyneuropathy occurred at the age of 34 for the proband (B1), whilst his brother (B2) is healthy 3 years after the onset of his brother's disease.

Discussion: In the following, a detailed description of the clinical presentation of the Swedish twin pairs is provided together with a discussion of possible environmental factors initiating the onset of the disease.