A Familial Analysis of Neurosarcoidosis Utilizing the Utah Population Database
Paul Crane1, Justin Abbatemarco2, Zhe Yu3, Ankita Date3, Myke Madsen3, Alison Fraser3, Ka-Ho Wong1, Jennifer Lord4, Tammy Smith1, Stacey Clardy1
1Neurology, University of Utah, 2Cleveland Clinic Foundation, 3Population Sciences, Huntsman Cancer Institute, 4Novant Health
Objective:
To investigate for evidence of familial clustering within a large cohort of patients with Neurosarcoidosis utilizing the Utah Population Database.
Background:
Sarcoidosis is a multisystemic inflammatory disease that can affect the cardiac, integumentary, hepatic, renal, ocular, and neurologic systems. Neurologic manifestations include cranial neuropathies, meningitis, peripheral neuropathy, myelopathy, intraparenchymal mass lesions. Current evidence suggests familial clustering of sarcoidosis in Sweden as well as within the US Black population. Genes of interest include HLA-DP subregions, Annexin A11, Butyrophilinlike 2 gene, and Toll-like receptors. We investigated for evidence of shared genetics among our Intermountain West cohort of neurosarcoidosis patients.
Design/Methods:
We performed a retrospective review of all definite and probable neurosarcoidosis patients diagnosed and managed at our institution. Using the Utah Population Database (UPDB), a population-based genealogic resource containing medical and demographic information of over 11 million individuals, we identified high-risk pedigrees with excess familial aggregation of neurosarcoidosis using the Familial Standardized Incidence Ratio (FSIR). Unaffected subjects were identified and matched 10:1 to neurosarcoidosis patients by age, birth year, and pedigree structure in the UPDB. Familial risk analyses were performed to estimate the heritability of neurosarcoidosis FDRs, SDRs, and TDRs separately using multivariate logistic regression adjusting for sex, birth year, race, and ethnicity.
Results:
Out of the 54 patients in the cohort, the median age of patients was 63 years (SD 12 years), 36(66%) were female and 46 (85%) self-identified as Caucasian. A total of 12 (22%) had definite neurosarcoidosis and 42 (78%) had probable neurosarcoidosis. The initial symptom of sarcoidosis was neurologic in 34 (63%) of the patients. We studied the inter-relatedness of the patients with neurosarcoidosis.
Conclusions:
Neurosarcoidosis is a rare disease and thought to be a manifestation of a multisystem disease in which familial clustering and genetic analysis suggests that inherited factors play a role in the pathogenesis which requires further investigation.