Author(s)
Natasha D. Dombrowski, BA
Youjin Li, MD
Cher X. Zhao, MD
Pankaj B. Agrawal, MBBS, MMSc
Reza Rahbar, DMD, MD
Affiliation(s)
1Department of Otolaryngology and Communication Enhancement, Boston Children's Hosp., Boston, MA, 2Department of Pediatrics, Boston Children's Hosp., Harvard Med. Sch., Boston, MA, 3Department of Otolaryngology and Communication Enhancement, Boston Children's Hosp., Harvard Med. Sch., Boston, MA.
Abstract:
Introduction: Laryngeal clefts (LCs) are rare congenital anomalies characterized by the failure of fusion of the posterior cricoid lamina or incomplete development of the tracheoesophageal septum. While most cases are sporadic, LC may be associated with other congenital anomalies or syndromes. Familial occurrence is not frequently reported in the literature but has been noted in our clinical experience. The goal of this research is to describe the existing literature and our own experience surrounding familial occurrence of LC that may help elucidate its underlying genetic basis.
Methods: Comprehensive literature search was conducted and retrospective chart review was performed on 8 sets of siblings diagnosed at our institution. Data assessed included demographics, type of cleft, and genetic findings.
Results: Laryngeal cleft appears to be mostly sporadic. Genetic testing is typically performed for variants in known genes associated with syndromic LC, such as MID1 for Opitz G, TBX1 for 22q11 microdeletion, GLI3 for Pallister Hall, and CHD7 and SEMA3E for CHARGE. Three case studies have been described in the literature with familial occurrence of LC which suggests an autosomal dominant inheritance pattern. We evaluated data at our institution and identified 19 patients from 8 families demonstrating familial occurrence of LC. Six (75%) families had 2 affected siblings, 1 family (12.5%) had 3 affected siblings, and 1 family (12.5%) had 4 affected siblings. About half the patients were male (10/19, 52.6%) which suggests no sex predilection. Fourteen patients (73.7%) had Type 1 clefts and 5 (26.3%) had Type 2 clefts. All patients were referred for genetic testing: 7 for clinical purposes and 11 for research studies.
Conclusion: Beyond a few known syndromes, LC has largely been thought to be sporadic. However, findings from the existing literature and our own experience with familial LC in eight families suggests genetic factors that are yet to be elucidated.