Asymptomatic laryngeal malformations are common in patients with Pallister-Hall syndrome

Abstract

Pallister-Hall syndrome (PHS) comprises hypothalamic hamartoma, polydactyly, pituitary dysfunction, laryngotracheal cleft, imperforate anus, and other anomalies. Some patients with PHS have a bifid epiglottis, a rare malformation. Greig cephalopolysyndactyly syndrome (GCPS) comprises polydactyly with craniofacial malformations without the PHS malformations. Both disorders are caused by mutations in the GLI3 gene. Laryngoscopy on 26 subjects with PHS showed that 15 had a bifid or cleft epiglottis (58%) and none of 14 subjects with GCPS had a cleft epiglottis. The malformed epiglottis was asymptomatic in all of the prospectively evaluated subjects. One additional PHS subject was found to have bifid epiglottis and a posterior laryngeal cleft on autopsy. We conclude that bifid epiglottis is common in PHS but not GCPS. Posterior laryngeal clefts are an uncommon manifestation of PHS and are identified only in severely affected patients. The diagnosis of a bifid epiglottis should prompt a thorough search for other sometimes asymptomatic anomalies of PHS to provide better medical care and recurrence risk assessment for affected individuals and families.

What you can learn from one gene: GLI3

“…27 Bifid epiglottis was present 15 of 26 patients with PHS, but all 15 were asymptomatic. 28 Thus many patients with PHS could erroneously be considered to have nonsyndromic polydactyly if they are not thoroughly evaluated.…”

Genetic players in esophageal atresia and tracheoesophageal fistula

“…Bifid epiglottis is common in PHS, but posterior laryngeal clefts are identified only in severely affected patients [34]. The causative mutations for PHS occur in the GLI3 gene.…”

Congenital Bilateral Saccular Cysts and Bifid Epiglottis: Presentation and Management

“…The most common defects are anomalies of the hands and/or feet (90 %), hypopituitarism and hypothalamic hamartomas (50 %), which is the primary feature of this syndrome [3,12]. Other manifestations of the syndrome include, imperforate anus, renal anomalies cleft palate, cleft uvula, and laryngeal malformations [12].…”

“…The most common congenital anomalies of the larynx with such a presentation include laryngomalacia (60 %), vocal cord paralysis (VCP) (10 %), and subglottic stenosis. Another rare cause is that of saccular disorders which almost always present with stridor [1][2][3].…”

“…Depending on whether it contains air, mucus or purulent material, the lesion is named either a laryngocele with a patent saccular orifice, a saccular cyst with a blocked orifice or a laryngopyocele respectively. Saccular cysts are extremely rare representing only 1.5 % of all laryngeal anomalies [3,4].…”