Population-based description of familial clustering of Chiari malformation Type I

作者：Abbott Diana; Brockmeyer Douglas; Neklason Deborah W; Teerlink Craig; Cannon Albright Lisa A^*

来源：Journal of Neurosurgery, 2018, 128(2): 460-465.

DOI：10.3171/2016.9.JNS161274

• Chiari malformation
• relative risk
• UPDB
• familiality
• skull base

OBJECTIVE A population-based genealogical resource with linked medical data was used to define the observed familial clustering of Chiari malformation Type I (CM-I).
METHODS All patients with CM-I were identified from the 2 largest health care providers in Utah; those patients with linked genealogical data were used to test hypotheses regarding familial clustering. Relative risks (RRs) in first-, second-, and third-degree relatives were estimated using internal cohort-specific CM-I rates; the Genealogical Index of Familiality (GIF) test was used to test for an excess of relationships between all patients with CM-I compared with the expected distribution of relationships for matched control sets randomly selected from the resource. Pedigrees with significantly more patients with CM-I than expected (p < 0.05) based on internal rates were identified.
RESULTS A total of 2871 patients with CM-I with at least 3 generations of genealogical data were identified. Significantly increased RRs were observed for first- and third-degree relatives (RR 4.54, p < 0.001, and RR 1.36, p < 0.001, respectively); the RR for second- degree relatives was elevated, but not significantly (RR 1.20, p = 0.13). Significant excess pairwise relatedness was observed among the patients with CM-I (p < 0.001), and borderline significant excess pairwise relatedness was observed when all relationships closer than first cousins were ignored (p = 0.051). Multiple extended high-risk CM-I pedigrees with closely and distantly related members were identified.
CONCLUSIONS This population-based description of the familial clustering of 2871 patients with CM-I provided strong evidence for a genetic contribution to a predisposition to CM-I.

• 出版日期2018-2