FinDis - Finnish Disease Database
HOME DISEASES ABOUT
Findis

Amyloidosis, finnish type (FAF)

Genes

Summary

Amyloidosis, Finnish type , also known as Familial amyloidosis, Finnish type (FAF) is a dominantly inherited amyloid depositing disorder caused by missense mutation at nucleotide c.654 of the gelsolin gene (GSN) at chromosome 9q32-34. The mutated gene product has a substitution of aspartic acid to asparagine or tyrosine at amino acid 214. The clinical findings of FAF are characterized by a slowly presenting triad of ocular, skin and neurological manifestations of adult age. Corneal lattice dystrophy, visible in slit-lamp examination, is the most characteristic and often the first disease manifestation. Corneal lattice dystrophy, common to all patients, usually begins during the third to fourth decade but it can be as late as at eigthies. Photophobia, general irritablity of the eyes, corneal erosions, inflammations and periodical visus impairment are frequent, while total permanent blindness is rare. The most significant neurological finding in FAF is the slowly progressing cranial neuropathy, usually presenting with facial palsy during the fourth or fifth decade. At later ages, lower cranial nerves can be involved resulting in severe bulbar paresis. Minor peripheral nerve involvement is seen in some cases. Dermatological signs include thickened and loose skin leading to cutis laxa after the fifth decade. The lax facial skin, palsies and muscle atrophy give a characteristic sad facial appearance, particularly in older patients. In rare homozygous patients, all disease manifestations appear earlier and in more severe form. All organ manifestations in FAF are caused by systemic deposition of amyloid fibrils composed of integral degradation fragments of variant gelsolin. Clinical diagnosis of FAF is mainly based on detection of corneal lattice dystrophy in slit-lamp examinations, and supported by other characteristic findings such as facial nerve paresis and cutis laxa. Gene tests for the mutation offer reliable laboratory diagnosis of both affected and symptomless gene carriers.

Links

UMLS Concept names

Selected publications

  • J Exp Med. 1990 Dec 1;172(6):1865-7. Mutation in gelsolin gene in Finnish hereditary amyloidosis. Levy E1, Haltia M, Fernandez-Madrid I, Koivunen O, Ghiso J, Prelli F, Frangione B. PMID: 2175344 (Pubmed)
  • FEBS Lett. 1990 Dec 10;276(1-2):75-7. Finnish hereditary amyloidosis is caused by a single nucleotide substitution in the gelsolin gene. Maury CP1, Kere J, Tolvanen R, de la Chapelle A. PMID: 2176164 (Pubmed)