AUTOSOMAL-DOMINANT PURE SPASTIC PARAPLEGIA - A CLINICAL, PARACLINICAL, AND GENETIC-STUDY

Objectives-At least three clinically indistinguishable but genetically different types of autosomal dominant pure spastic paraplegia (ADPSP) have been described. In this study the clinical, genetic, neurophysio logical, and MRI characteristics of ADPSP were investigated. Methods-S ixty three at risk members from five families were clinically evaluate d. A diagnostic index was constructed for the study. Microsatellite ge notypes were determined for chromosomes 2p, 14q, and 15q markers and m ultipoint linkage analyses were performed. Central motor conduction ti me studies (CMCT), somatosensory evoked potential (SSEP) measurement, and MRI of the brain and the total spinal cord were carried out in 16 patients from four families. Results-The clinical core features of ADP SP were homogeneously expressed in all patients but some features were only found in some families and not in all the patients within the fa mily. In two families non-progressive ''congenital'' ADPSP was seen in some affected members whereas adult onset progressive ADPSP was prese nt in other affected family members. As a late symptom not previously described low backache was reported by 47%. Age at onset varied widely and there was a tendency for it to decline in successive generations in the families, suggesting anticipation. Genetic linkage analysis con fined the ADPSP locus to chromosome 2p21-p24 in the five families. The led scores obtained by multipoint Linkage analysis were positive with a combined maximum lod score of Z=8.60. The neurophysiological studie s only showed minor and insignificant prolongation of the central moto r conduction time and further that peripheral conduction and integrity of the dorsal columns were mostly normal. Brain and the total spinal cord MRI did not disclose any significant abnormalities compared with controls. Conclusions-ADPSP linked to chromosome 2p21-p24 is a phenoty pic heterogeneous disorder characterised by both interfamilial and int rafamilial variation. In some families the disease may be ''pure'' but the existence of ''pure plus'' families is suggested in others. The n europhysiological and neuroimaging investigations did not show any maj or abnormalities.