Supranuclear Palsy, Progressive, 2

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Retrieved
2019-09-22
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Trials

For a phenotypic description and a discussion of genetic heterogeneity of progressive supranuclear palsy (PSP), see PSNP1 (601104).

Clinical Features

De Yebenes et al. (1995) studied a 5-generation Spanish family in which progressive supranuclear palsy was transmitted as an autosomal dominant trait. The proband had the classic presentation of this disorder beginning with axial rigidity, slowness of movement, and gait difficulty. Over the course of 2 years he progressed to complete vertical gaze palsy, axial dystonia, and retrocollis, as well as generalized severe akinesia. Postmortem examination demonstrated neuronal loss and atrophy of the brainstem, cerebellum, and diencephalon. There were also neurofibrillary tangles and gliosis without prominent senile plaques, the same pathology that was observed in the sporadic cases of progressive supranuclear palsy originally reported by Steele et al. (1964). Rojo et al. (1999) reported clinical findings on an additional 25 family members.

Ros et al. (2005) reported follow-up on the family originally reported by de Yebenes et al. (1995). Four members had typical PSP, characterized by supranuclear gaze palsy, dysarthria, dysphagia, akinesia, rigidity, postural tremor, and frontal lobe dysfunction. At least 5 ancestors were reportedly affected. Several asymptomatic or mildly symptomatic individuals showed abnormal neuroimaging results on PET scan, including decreased dopa uptake and/or reduced frontal lobe glucose metabolism; these individuals were considered to be presymptomatic and thus affected (Piccini et al., 2001).

Mapping

By genomewide linkage analysis of the large family with PSP, Ros et al. (2005) achieved a maximum multipoint lod score of 3.53 between markers D1S428 and D1S461 assuming autosomal dominant inheritance and 90% penetrance. Haplotype analysis identified a 3.4-cM candidate disease locus between markers D1S238 and D1S2823 on chromosome 1q31.1. Ros et al. (2005) noted that the power of the linkage analysis was increased by detecting presymptomatic individuals with PET scans and assuming that they were affected. No linkage was found to the MAPT gene (157140) on chromosome 17q21.