Spastic Paraplegia 29, 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. (2005) reported a large family of Scottish descent in which 19 members were affected with spastic paraplegia inherited in an autosomal dominant pattern. The mean age at onset was 15.2 years, and most patients had spasticity and hyperreflexia of the lower limbs with extensor plantar responses. Two patients had hyperreflexia of the upper limbs. Other features included sensorineural hearing impairment, pes cavus, clonus, and neonatal hyperbilirubinemia without kernicterus. Six patients had urinary urgency due to detrusor muscle hyperactivity. Thirteen patients had a hiatal hernia, including 10 paraesophageal and 3 sliding. There was a general impression of genetic anticipation, manifest by earlier age at onset and increasing disease severity in subsequent generations.

Mapping

By genomewide analysis of a Scottish family with autosomal dominant spastic paraplegia, Orlacchio et al. (2005) identified a 22.3-cM candidate disease locus, designated SPG29, on chromosome 1p31.1-p21.1 (maximum multipoint lod score of 7.80 at marker D1S2865). Affected family members shared a common haplotype flanked by D1S2889 and D1S248.