Familial occurrence and heritable connective tissue disorders in spontaneous intracranial hypotension

BACKGROUND AND PURPOSE: Genetic factors often are implicated in the etiology and pathogenesis of spontaneous spinal CSF leaks. Nevertheless, the familial occurrence of spontaneous intracranial hypotension (SIH) and the prevalence of heritable connective tissue disorders (hCTDs) have never been studied in large patient series. The purpose of this study was to determine the frequency of familial SIH and of hCTDs in a large cohort of patients with SIH. METHODS: In this single-center retrospective observational study, data elements indicating familial SIH and presence of hCTDs were extracted from a prospectively maintained data base. In this data base, the patients’ clinical characteristics, including family history of SIH and diagnosis of hCTD, are abstracted prospectively and updated with each change or addition to the data elements. We studied the time-period between 1/1/2001 and 12/31/2023. RESULTS: Among 1945 SIH patients, twelve patients (0.62%) from nine different families (0.46%) had a family history of SIH (twelve patients were evaluated in person and six patients were not evaluated in person). There were two affected family members in each family. The 18 affected family members included two men and 16 women (mean age: 44.2 years (range, 21-65 years)). Three patients of two different families with a family history of SIH had been diagnosed with a monogenetic hCTD. Overall, 41 (2.1%) of the 1945 patients had a monogenetic hCTD. Thus, three patients (7.3%) from two families (4.9%) of 41 SIH patients with a monogenetic hCTD had a family history of SIH compared to ten patients (0.53%) from seven families (0.37%) among 1904 SIH patients who did not have a monogenetic hCTD (p=.0015). CONCLUSIONS: The occurrence of SIH among first-degree family members suggests the importance of genetic factors but is rare and hCTDs are uncommon among the entire SIH population. These findings support the notion that SIH is a multifactorial disorder. Further research is crucial to elucidate genetic and acquired factors in the development of spontaneous spinal CSF leaks. For now, patients can be reassured that the risk of, for example, their offspring developing a spontaneous CSF leak - a commonly voiced concern - is not particularly high.