Spastic Paraplegia 38, Autosomal Dominant

For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600).

Clinical Features

Orlacchio et al. (2008) reported a large 4-generation Italian family in which 19 individuals had autosomal dominant spastic paraplegia. The mean ages at onset in the lower and upper limbs were 16.8 and 18.5 years, respectively. All patients presented with spastic gait resulting from mild to severe spasticity in the lower limbs and occasionally by additional weakness of the foot extensor. All patients had pyramidal tract signs characterized by hyperreflexia and extensor plantar responses; most had pes cavus. All patients except 2 had atrophy of the small hand muscles, which appeared after the gait difficulties. Sensation was generally normal, but 2 individual had moderately impaired vibration sensation in the ankles. One patient was wheelchair-bound. Electrophysiology showed abnormalities in both the upper and lower motor neurons. Orlacchio et al. (2008) noted that the clinical features in this family were similar to those of Silver syndrome (SPG17; 270685).

Mapping

By genomewide linkage analysis of a large Italian family with autosomal dominant SPG, Orlacchio et al. (2008) found linkage to a 13.1-cM (6.9-Mb) interval on chromosome 4p16-p15 between D4S432 and D4S1599 (maximum 2-point lod score of 3.30 at D4S2935). The locus was designated SPG38.