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A Clinical and Genealogical Investigation

Karin Axelman, RNT; Hans Basun, MD, PhD; Bengt Winblad, MD, PhD; Lars Lannfelt, MD, PhD

Arch Neurol. 1994;51(12):1193-1197.

Abstract
Objective
To describe clinical and genealogic features in a Swedish family with Alzheimer's disease with a double mutation of the amyloid precursor protein gene at codon 670/671 and to study the effects of anticipation and imprinting.

Design
Interviews with relatives, clinical investigations of the diseased, pedigree analysis, studies of medical records, and comparison with other families affected by Alzheimer's disease with amyloid precursor protein mutations.

Setting
The Alzheimer's Disease Research Centre, Department of Clinical Neuroscience, Section of Geriatric Medicine, Karolinska Institute, Huddinge (Sweden) University Hospital.

Patients and Other Participants
Individuals with the amyloid precursor protein codon 670/671 mutation and their relatives (N=66).

Results
The trait was traced through eight generations, and an autosomal dominant inheritance with very high penetrance was observed. Onset occurred between 44 and 61 years of age (mean, 53 years). The mean duration of disease was 8.5 years (range, 3 to 13 years). The earliest clinical manifestations were deficits in memory function and abstract reasoning. Myoclonic jerks and seizures were common symptoms late in the disease. Anticipation and imprinting effects were not found in this family.

Conclusions
The disease in this family has a single origin—a double mutation in the amyloid precursor protein gene at codon 670/671 transmitted as an autosomal dominant trait. The wide range in age at onset and the clinical symptoms in this pedigree give a characteristic phenotype similar to that seen in some of the other pedigrees with amyloid precursor protein mutations.

Author Affiliations
From the Department of Clinical Neuroscience, Section of Geriatric Medicine, Karolinska Institute, Huddinge (Sweden) University Hospital.

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