Familial subarachnoid hemorrhage: Distinctive features and patterns of inheritance

Abstract

To delineate the distinctive features of familial subarachnoid hemorrhage, we compared gender and age at the time of subarachnoid hemorrhage, as well as site and number of aneurysms, in patients with familial subarachnoid hemorrhage (at least 1 first-degree relative with subarachnoid hemorrhage) and patients with sporadic subarachnoid hemorrhage (no subarachnoid hemorrhage in first- or second-degree relatives), in a prospective, hospital-based series of patients. In addition we studied the pattern of inheritance in 17 families with familial subarachnoid hemorrhage. Mean age at the time of hemorrhage in patients with the familial form was 6.8 years lower than that in those with the sporadic form, and middle cerebral artery aneurysms occurred more often in patients with familial disease. Sex distribution and number of aneurysms were similar in the two groups. Inheritance was compatible with autosomal dominant transmission in some families, and with autosomal recessive or multifactorial transmission in others. In our 5 families as well as in all 18 previously reported families with two affected generations, the age at the time of subarachnoid hemorrhage was invariably lower in later generations, which is suggestive of anticipation. We conclude that familial subarachnoid hemorrhage is a separate entity with occurrence at a young age, predilection for aneurysms of the middle cerebral artery, and variable modes of inheritance, including autosomal dominant inheritance with possible anticipation.

Familial Intracranial Aneurysms

“…Those studies have consistently shown that familial aneurysms rupture earlier and are smaller in size compared with sporadic aneurysms 3,4,10,19) . In siblings, aneurysms more commonly rupture within the same decade of life 7) .…”

“…Nevertheless, in Korea, cerebrovascular disease remains the second most common cause of death, following cancer, and subarachnoid hemorrhage (SAH) is the third major type of stroke 13) . SAH affects 8-10 per 100,000 persons per year 4,18) . Most SAHs are attributable to the rupture of an intracranial aneurysm, and 25-50% of those patients die as a result 6,18) .…”

“…The familial aggregation of intracranial aneurysms was first described in 1954 by Chambers and colleagues in a report on the cases of a father and son who each had an intracranial aneurysm 5) . Numerous studies comparing the characteristics of familial intracranial aneurysms with those of non-familial (sporadic) aneurysms have found that familial aneurysms rupture about 5 years earlier, on average, and are smaller than sporadic aneurysms; are underrepresented in the anterior communicating artery; and frequently occur as multiple aneurysms 4,7,11,19) . To compare the characteristics of familial SAH in our community with those reported in previous studies, we evaluated a series of patients with SAH who had at least one first-degree relative with SAH.…”

Anticipation in familial intracranial aneurysms in consecutive generations

“…1 The incidence of SAH varies between seven and 20 per 100 000 persons per year and approximately 10% of the patients report a positive family history. 2,3 Bromberg et al 3 suggested that SAH in the consecutive generations occurred at an earlier age as compared to previous generations. In both sporadic and in familial cases SAH occurs more frequently in women than in men.…”

“…6 As based on autopsy studies about 2 -3% of the population has an asymptomatic IA, in familial cases the prevalence is estimated at 9.5 -10.5%. 3 Over 200 families have been described since the first report on the familial occurrence of IA was presented by Chambers in 1954. 7,8 Segregation analysis did not reveal one mode of inheritance, both autosomal recessive (AR) and autosomal dominant (AD) patterns of inheritance have been described.…”