What syndrome is associated with a laryngeal (voice box) cleft?

From the Guidelines

Laryngeal clefts are commonly associated with 22q11.2 deletion syndrome, as well as other genetic disorders such as Opitz G/BBB syndrome, CHARGE syndrome, Pallister-Hall syndrome, VACTERL association, and DiGeorge syndrome. These conditions involve multiple organ systems beyond the laryngeal defect and are associated with various congenital anomalies, including airway anomalies such as laryngomalacia, tracheomalacia, subglottic stenosis, glottic web, vocal fold paralysis, and esophageal atresia 1. The association between these syndromes and laryngeal clefts stems from disruptions in embryological development during the critical period when the trachea and esophagus separate. Some studies have reported that laryngotracheal anomalies, including laryngeal clefts, are a known association with esophageal atresia-tracheoesophageal fistula (EA-TEF), with rates of secondary airway lesions ranging from 20% to 40% 1. Management of laryngeal clefts requires a multidisciplinary approach involving otolaryngologists, pulmonologists, gastroenterologists, and geneticists, with treatment depending on the severity of the cleft, ranging from conservative management for minor clefts to surgical repair for more severe cases. Key considerations in the management of these patients include:

• Early identification of associated syndromes and congenital anomalies
• Routine airway evaluation and screening for symptoms of aspiration and respiratory distress
• Multidisciplinary management involving various specialties
• Individualized treatment plans based on the severity of the laryngeal cleft and associated conditions.

From the Research

Syndromes Associated with Laryngeal Cleft

• Laryngeal cleft is associated with several syndromes, including:
  • G syndrome (Opitz-Frias Syndrome) 2
  • Pallister-Hall syndrome 3, 4
  • CHARGE syndrome 4
  • VATER/VACTERL syndrome 4
  • Opitz syndrome (BBB Syndrome) 2
• These syndromes often present with a range of congenital anomalies, including:
  • Midline defects (e.g. cleft lip and palate, hypertelorism) 2
  • Tracheoesophageal fistula 3
  • Congenital heart defects 3
  • Genitourinary anomalies 4
  • Craniofacial anomalies 4
• Laryngeal cleft can also occur in isolation or as part of a developmental field defect 3

Clinical Presentation

• Patients with laryngeal cleft often present with respiratory symptoms, such as:
  • Stridor 5, 3, 4
  • Chronic cough 4
  • Aspiration 5, 4
  • Recurrent respiratory infections 4
• Feeding difficulties and dysphagia are also common 5, 2

Genetic Factors

• While most cases of laryngeal cleft are sporadic, there is evidence of familial occurrence 6
• Genetic findings are available for a limited number of patients, but suggest that additional genetic factors may be involved 6