Clinical genetics of familial progressive supranuclear palsy

Recent studies have shown that progressive supranuclear palsy (PSP) could b e inherited, but the pattern of inheritance and the spectrum of the clinica l findings in relatives are unknown. We here report 12 pedigrees, confirmed by pathology in four probands, with familial PSP. Pathological diagnosis w as confirmed according to recently reported internationally agreed criteria . The spectrum of the clinical phenotypes in these families was variable in cluding 34 typical cases of PSP (12 probands plus 22 secondary cases), thre e patients with postural tremor, three with dementia, one with parkinsonism , two with tremor, dystonia, gaze palsy and ties, and one with gait disturb ance, The presence of affected members in at least two generations in eight of the families and the absence of consanguinity suggests autosomal domina nt transmission with incomplete penetrance. We conclude that hereditary PSP is more frequent than previously thought and that the scarcity of familial cases may be related to a lack of recognition of the variable phenotypic e xpression of the disease.