Familial Chiari Malformation: Prevalence of Connective Tissue Disorders and Other Comorbidities

BACKGROUND AND OBJECTIVES: Chiari malformation type 1 (CM-I) is frequently associated with connective tissue disorders (CTDs), particularly Ehlers-Danlos syndrome (EDS), which may increase surgical risk and complicate management. Familial clustering of CM-I and CTDs has been reported, but their prevalence within families remains underexplored. This study aimed to determine the prevalence of CTDs and comorbidities among family members of CM-I patients, comparing familial and sporadic cases. METHODS: We conducted a retrospective survey-based study of patients who underwent posterior fossa decompression for CM-I between 2008 and 2023 by the senior author. Eligible patients (n = 890) were invited to complete a 10-item questionnaire regarding family history of CM-I, CTDs, and related comorbidities. Responses were stratified into familial (≥1 relative with CM-I) and sporadic groups. Group comparisons were performed using χ2 or Fisher exact tests. RESULTS: Of 354 complete responses, 308 (87.0%) reported a family history of CM-I. Compared with sporadic cases, familial CM-I patients more often reported a family history of joint replacement or surgery (59.1% vs 39.5%, P = .0162), joint dislocation/injury (58.5% vs 16.7%, P < .0001), easy bruising (80.0% vs 57.1%, P = .0010), and CTDs (53.4% vs 18.9%, P < .0001), with EDS being the most common. Familial CM-I respondents were also more likely to report hyperflexibility (69.4% vs 47.7%, P = .0045) and systemic comorbidities, including postural orthostatic tachycardia syndrome (24.0% vs 13.0%) and mast cell activation disorder (9.4% vs 0%). CONCLUSION: Familial CM-I is strongly associated with CTDs, particularly EDS, and systemic comorbidities such as hypermobility, postural orthostatic tachycardia syndrome, and mast cell activation disorder. These findings support a heritable link between CM-I and CTDs and highlight the importance of detailed family history and connective tissue evaluation in CM-I patients. Comprehensive assessment and counseling of at-risk relatives may improve diagnosis, surgical planning, and long-term outcomes.