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Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2004 Oct;75(10):1436–1442. doi: 10.1136/jnnp.2003.025098

Anticipation and phenotype in familial intracranial aneurysms

Y Ruigrok 1, G Rinkel 1, C Wijmenga 1, J van Gijn 1
PMCID: PMC1738765  PMID: 15377692

Abstract

Background: In familial intracranial aneurysms there is evidence for genetic heterogeneity, probably from mutations at separate loci.

Objectives: To compare demographic and clinical features in patients of families with familial intracranial aneurysm and different patterns of inheritance; and to compare the ages of patients with subarachnoid haemorrhage (SAH) in affected parent–child pairs to determine whether there is anticipation.

Methods: Pedigrees for 53 families with familial intracranial aneurysms were constructed, divided into patterns of inheritance suggestive or not suggestive of autosomal dominant transmission. Demographic and clinical features were compared. The age at time of SAH in affected parent–child pairs was compared using the Wilcoxon test.

Results: No differences in demographic or clinical features were found between families compatible with an autosomal dominant pattern of inheritance and those with a non-dominant pattern. In families with affected members in two successive generations the age at time of SAH in parents was 55.2 years and in children 35.4 years (mean difference, 19.8 years, p<0.001).

Conclusions: Phenotypes are similar in families with and without a probable autosomal dominant pattern of inheritance. Thus in future genetic studies on familial intracranial aneurysms, stratification according to phenotype is not likely to be useful. Anticipation probably occurs, as affected parents are significantly older at the time of SAH than their affected children.

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Selected References

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