FAMILIAL PROGRESSIVE SUPRANUCLEAR PALSY - DESCRIPTION OF A PEDIGREE AND REVIEW OF THE LITERATURE

We describe a family with autosomal dominant progressive supranuclear palsy (PSP) involving five generations which was confirmed in one pati ent. The proband presented with progressive slowness at age 53 years, followed by ocular palsy, loss of balance, axial dystonia, dysphagia a nd dysarthria, and died at age 59 years. Neuropathological examination revealed moderate numbers of neurofibrillary tangles without prominen t senile plaques in the cortex, and neuronal loss, gliosis and moderat e to severe accumulation of tangles in the basal ganglia and brainstem . Other affected relatives, including the proband's sister father pate rnal uncle, and other members of earlier generations presented with no n-characteristic akinetic syndromes, which progressed towards more typ ical PSP only after several years of disease. A review of the literatu re revealed six other families with neurodegenerative disorders associ ated with pathological findings compatible with PSP in at least one me mber: The clinical symptoms varied greatly between individuals in thes e families. The pattern of inheritance seems compatible with autosomal dominant transmission, although other patterns of transmission could not be excluded We conclude that there is art autosomal dominant form of PSP and that the number of hereditary cases may be greater than pre viously thought. The rarity of familial cases of PSP could be attribut ed to diagnostic problems, including lack of recognition of atypical c ases and death of the gene carriers before the age of appearance of th e clinical symptoms. Large families with hereditary PSP could provide an adequate point of departure for investigation of the gene defect re sponsible for this disease.