Familial Aggregation in Idiopathic Subglottic Stenosis

Abstract

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 iSGS¹⁰⁰⁰ 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 (P = .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.

Keywords: idiopathic subglottic stenosis; laryngotracheal stenosis.

Figure 1.

Sample pedigrees. A filled-in marker denotes idiopathic subglottic stenosis. (A) Paternally related mother-daughter pairs. (B) Affected sisters. (C) A mother-daughter pair. (D) A father-daughter pair.