OBJECTIVE - To evaluate inheritance patterns and define the familial clustering rate of idiopathic subglottic stenosis (iSGS).
STUDY DESIGN - Retrospective observational study.
SETTING - International multicenter collaborative of >30 tertiary care centers.
METHODS - Patients with a clinically confirmed iSGS diagnosis within the North American Airway Collaborative's iSGS cohort consented between 2014 and 2018 were eligible for enrollment. Patient demographics and disease severity were abstracted from the collaborative's iSGS longitudinal registry. Pedigrees of affected families were created.
RESULTS - A total of 810 patients with iSGS were identified. Positive family history for iSGS was reported in 44 patients in 20 families. The rate of familial clustering in iSGS is 2.5%. Mean age of disease onset is 42.6 years. Of the 44 patients with familial aggregation of iSGS, 42 were female and 2 were male; 13 were mother-daughter pairs and 2 were father-daughter pairs. There were 3 sister-sister pairs. There was 1 niece-aunt pair and 2 groups of 3 family members. One pedigree demonstrated 2 affected mother-daughter pairs, with the mothers being first-degree paternal cousins. Inheritance is non-Mendelian, and anticipation is present in 11 of 13 (84%) parent-offspring pairs. The mean age of onset between parents (48.4 years) and offspring (36.1 years) was significantly different ( = .016).
CONCLUSION - This study quantifies the rate of familial clustering of iSGS at 2.5%. Inheritance is non-Mendelian, and disease demonstrates anticipation. These data suggest that there may be a genetic contribution in iSGS.