AUTOSOMAL-DOMINANT CEREBELLAR-ATAXIA WITH RETINAL DEGENERATION (ADCA-II) - CLINICAL AND NEUROPATHOLOGICAL FINDINGS IN 2 PEDIGREES AND GENETIC-LINKAGE TO 3P12-P21.1

Objectives - To investigate relations between clinical and neuropathol ogical features and age of onset, presence of anticipation, and geneti c linkage in autosomal dominant cerebellar ataxia type II (ADCA II). M ethods - The natural history of ADCA II was studied on the basis of cl inical and neuropathological findings in two pedigrees and genetic lin kage studies were carried out with polymorphic DNA markers in the larg est, four generation, pedigree. Results - Ataxia was constant in all a ge groups. Retinal degeneration with early extinction of the electrore tinogram constituted an important component in juvenile and early adul t (< 25 years) onset but was variable in late adult presentation. Neur omuscular involvement due to spinal anterior horn disease was an impor tant contributing factor to illness in juvenile cases. Postmortem find ings in four patients confirm the general neurodegenerative nature of the disease, which includes prominent spinal anterior horn involvement and widespread involvement of grey and white matter. Genetic linkage was found with markers to chromosome 3p12-p21.1 (maximum pairwise lod store 4.42 at D3S1285). Conclusions - The sequence of clinical involve ment seems related to age at onset. Retinal degeneration is variable i n late onset patients and neuromuscular features are important in pati ents with early onset. Strong anticipation was found in subsequent gen erations. Linkage of ADCA II to chromosome 3p12-p21.1 is confirmed.