Laryngeal Web, Familial

Description

Congenital laryngeal (glottic) webs are uncommon, membrane-like structures that extend across the laryngeal lumen near the level of the vocal cords. They are thought to result from incomplete resorption of an epithelial layer that normally obliterates the developing laryngeal opening at about the sixth week of embryologic life. This layer is usually completely eliminated by the tenth week. Most laryngeal webs occur at the glottic level and affect the vocal cords. More than 90% are located anteriorly and extend toward the arytenoids. While affected persons may have onset of manifestations at any age, with hoarse or weak voice and frequent upper respiratory infections, they usually manifest the condition as infants, with respiratory distress, stridor, and an unusual cry (Strakowski et al., 1988; Singh et al., 2009).

Clinical Features

Cohen (1985) divided laryngeal (glottic) webs into 4 types based on their appearance and an estimation of the degree of airway obstruction. Type 1 glottic webs are uniform in thickness with no subglottic extension; they compromise less than 35% of the airway and there is usually no airway obstruction. Type 2 glottic webs are slightly thicker, with a significantly thicker anterior component. Subglottic involvement is minimal. The web restricts the airway by 35 to 50% and usually causes little airway distress. Type 3 glottic webs are thick; the anterior portion of the web is solid, extends into the subglottis, and the true vocal cords are not well delineated. The web restricts the airway to 50 to 75%, and obstruction is moderately severe. Type 4 glottic webs are uniformly thick and extend into the subglottic area with resulting subglottic stenosis, occluding 75 to 90% of the airway. Respiratory obstruction is severe, and the patient is almost always aphonic (summary by Singh et al., 2009).

Howie et al. (1961) described subglottic bar in a grandfather, mother, and 2 daughters (4 persons in 3 generations). Severe dyspnea with respiratory infection in a 6-year-old brought the condition to attention. All 4 had a harsh, quivering, high-pitched, weak voice and 3 had suffered from respiratory distress with inspiratory stridor. Imperfect adduction of the vocal cords was an associated finding.

Inheritance

Strakowski et al. (1988) found fewer than 10 reported families with laryngeal webs, 6 of which were reported before 1910. Strakowski et al. (1988) described 5 affected individuals in 3 generations of a family and suggested autosomal dominant inheritance. Three of the 5 were males, but there was no instance of male-to-male transmission.

Cytogenetics

Laryngeal web associated with deletions and microdeletions of 22q11.2, with or without signs of the velocardiofacial syndrome (192430) or DiGeorge syndrome (188400), was noted by Gay et al. (1981), Driscoll et al. (1992), Lindsay et al. (1995), and Fokstuen et al. (1997).

Fokstuen et al. (1997) observed type III laryngeal atresia (glottic web) in 3 patients with 22q11.2 microdeletion. One patient showed a 'classic' 22q11.2 deletion phenotype with clinical overlap with DiGeorge syndrome and velocardiofacial syndrome. However, the pattern of congenital anomalies in the 2 others was less specific, heart defects and minor anomalies being the only outstanding clinical manifestations suspicious for monosomy 22q11.2. Fokstuen et al. (1997) suggested that laryngeal atresia represents an additional malformation that should prompt investigation of the 22q11.2 deletion, especially in combination with congenital heart defects.

Stoler et al. (1998) reported a laryngeal web in 2 additional children with 22q11 deletions.

Marble et al. (1998) evaluated a mother and son, both of whom had congenital subglottic web and 22q11.2 deletion. The son, a neonate, had interrupted aortic arch, small ears, downsloping palpebral fissures, and micrognathia, as well as hypocalcemia. The mother had had a weak cry neonatally and hoarseness of the voice during early childhood. Subglottic web was discovered at the age of 4 years and was excised, leading to significant improvement in her voice but some residual hoarseness. Her serum calcium was normal.