Co-segregation of Huntington disease and hereditary spastic paraplegia in 4 generations.

ABSTRACT

INTRODUCTION: Huntington disease (HD) is an autosomal dominant neurodegenerative disease characterized by choreic hyperkinesias, cognitive decline, and psychiatric manifestations, caused by an increased number of CAG repeats in the IT15 gene on chromosome 4p16.3. Silver syndrome is a rare autosomal dominant form of complicated hereditary spastic paraplegia, characterized by lower limb spasticity in addition to amyotrophy of the small muscles of the hands. In addition to the previously identified locus SPG17 on chromosome 11q12-q14, a new locus (SPG38) on chromosome 4p16-p15 has been recently identified, a region that includes the HD gene. REPORT OF THE CASES We present a Greek family with 5 members diagnosed with HD in 4 generations. All affected members also presented with clinical features of Silver syndrome showing severe spastic paraplegia and prominent atrophy of all small hand muscles bilaterally. None of the other family members showed features of either HD or spastic paraplegia. CONCLUSIONS: The reported coexistence of Silver syndrome with HD in 4 generations is not fortuitous, suggesting that these 2 distinct genetic disorders are in linkage disequilibrium. Although rare, it is reasonable to expect additional similar cases. Clinical neurologists should perhaps investigate this possibility in cases combining features of HD and involvement of the upper and lower motor neurons.