Familial abdominal aortic aneurysms: collection of 233 multiplex families.
OBJECTIVE
This study investigated a large number of families in which at least two individuals were diagnosed with abdominal aortic aneurysms to identify the relationship of the affected relatives to the proband.


METHODS
Families for the study were recruited through various vascular surgery centers in the United States, Finland, Belgium, Canada, the Netherlands, Sweden, and the United Kingdom and through our patient recruitment website (www.genetics.wayne.edu/ags).


RESULTS
We identified 233 families with at least two individuals diagnosed with abdominal aortic aneurysms. The families originated from nine different nationalities, but all were white. There were 653 aneurysm patients in these families, with an average of 2.8 cases per family. Most of the families were small, with only two affected individuals. There were, however, six families with six, three with seven, and one with eight affected individuals. Most of the probands (82%) and the affected relatives (77%) were male, and the most common relationship to the proband was brother. Most of the families (72%) appeared to show autosomal recessive inheritance pattern, whereas in 58 families (25%), abdominal aortic aneurysms were inherited in autosomal dominant manner, and in eight families, the familial aggregation could be explained by autosomal dominant inheritance with incomplete penetrance. In the 66 families where abdominal aortic aneurysms were inherited in a dominant manner, 141 transmissions of the disease from one generation to another were identified, and the male-to-male, male-to-female, female-to-male, and female-to-female transmissions occurred in 46%, 11%, 32%, and 11%, respectively.


CONCLUSIONS
Our study supports previous studies about familial aggregation of abdominal aortic aneurysms and suggests that first-degree family members, male relatives, in particular, are at increased risk. No single inheritance mode could explain the occurrence of abdominal aortic aneurysms in the 233 families studied here, suggesting that abdominal aortic aneursyms are a multifactorial disorder with multiple genetic and environmental risk factors.
Kuivaniemi
Helena
H
Center for Molecular Medicine and Genetics and Department of Surgery, Wayne State University School of Medicine, Detroit, MI 48201, USA. kuivan@sanger.med.wayne.edu
Shibamura
Hidenori
H
Arthur
Claudette
C
Berguer
Ramon
R
Cole
C William
CW
Juvonen
Tatu
T
Kline
Ronald A
RA
Limet
Raymond
R
Mackean
Gerry
G
Norrgård
Orjan
O
Pals
Gerard
G
Powell
Janet T
JT
Rainio
Pekka
P
Sakalihasan
Natzi
N
van Vlijmen-van Keulen
Clarissa
C
Verloes
Alain
A
Tromp
Gerard
G
D017544:Aortic Aneurysm, Abdominal / Q000209:etiology* / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D012307:Risk Factors; D012737:Sex Factors