Laryngeal Clefts

This article is explains the background, grading an embryology of laryngeal clefts. Furthermore it describes possibles associations with other disorders and shows what methods can be used to repair the laryngeal clefts after a proper diagnosis. Just click on the links listed in the overview to read more about the specific subject.

OVERVIEW

BACKGROUND

  • AKA laryngotracheoesophagealcleft
  • rare congenital malformation resulting from failure of the fusion of the tracheoesophagealseptum, posterior cricoid lamina, or arytenoid mucosa
  • abnormal communication between the laryngotrachealcomplex and the pharyngoesophagealcomplex
  • range in severity depending on its inferior extension

HISTORY

  • 1792 first described by Richter
  • 1955 first successful repair by Pettersson
  • 1979 first endoscopic repair by Yamashita
  • 1987 Tucker described submucouscleft
  • 1989 Benjamin and Inglisdeveloped classification system most widely used today
  • 2006 Sandumodified classification system

EPIDEMIOLOGY

  • incidence 0.2-1.5%
  • likely underestimated
  • in children examined by laryngoscopy, incidence is between 6.2 and 7.6%
  • M:F ratio 1.2-1.5:1

Laryngeal cleft types

GRADING

  • Many classifications proposed
  • All based on the downward extension of the cleft
  • Descriptive—allows comparison of patients in the literature
  • Therapeutic—influences the choice of reconstruction and surgical technique
  • Prognostic—successful treatment and survival rates are highly correlated to the extension of cleft

Laryngeal cleft types

  • Type 0: submucosalcleft
  • Type I: supraglottic, interarytenoidcleft, above the vocal fold level
  • Type II: cleft extending below the vocal folds into the cricoid cartilage
  • Type III a: cleft extending through the cricoid cartilage but not into the trachea
  • Type III b: cleft extending through the cricoid cartilage and into the cervical trachea
  • Type IVa: cleft extending to the carina
  • Type IVb: cleft extending into one main bronchus

 

EMBRYOLOGY

Laryngeal cleft embryologie

Laryngeal cleft embryologie

  • Branchial arch derivatives
  • pharyngeal constrictors
  • laryngeal musculature, cartilages
  • Foregut derivatives
  • lower respiratory tract
  • esophagus
  • stomach, duodenum, liver, pancreas, and biliary apparatus

Laryngeal cleft embryology week 5 - 8

  • larynx develops from branchial arches IV-VI
  • paired arytenoid swellings develop giving the primitive glottis a T-shaped appearance and reducing the laryngeal lumen to a slit
  • laryngeal cartilages develop within the arytenoid swellings from the cartilage bars of the branchial arches
  • (epiglottis develops from the caudal half of the hypobranchialeminence, a derivative of branchial arches III and IV)
  • branchial arch VI will give rise to the interarytenoidmuscle (along with all intrinsic laryngeal muscles) and the cricoid cartilage

Laryngeal cleft embryology 7 months to week 9

  • the entrance to larynx ends blindly between weeks 7-10 as mesenchyme proliferates, then recanalizesand forms laryngeal aditus
  • laryngeal ventricles form and are bound cranially and caudally by future false and true vocal folds
  • laryngeal muscles develop from muscle elements in branchial arches IV-VI

Laryngeal cleft pharyngeal arch derivatives

Laryngeal cleft embryology week 4 - 5

  • laryngotracheal groove is seen in week 4 as a longitudinal groove in pharyngeal floor
  • externally seen as a ridge
  • the lining of the laryngotracheal groove forms the epithelium and glands of the larynx, trachea, bronchi, and lungs
  • splanchnic mesenchyme around the foregut gives rise to the connective tissue, the cartilage, and smooth muscle that forms the lower respiratory tract, esophagus, stomach, duodenum, liver, pancreas, and biliary apparatus
  • laryngotracheal groove deepens and grows caudally to become a diverticulum, lung bud
  • as diverticulum grows, it becomes separated from the pharynx by the tracheoesophagealseptum

Laryngeal cleft embryology week 4 - 6

Laryngeal cleft embryology week 8

  • esophagus separated from trachea by tracheoesophagealseptum
  • esophagus elongates rapidly and is final relative length at week 7
  • endoderm of esophagus initially proliferates and almost obliterates the lumen then recanalizesnear the end of the embryonic period

Laryngeal cleft embryology week 3 - 4

Laryngeal cleft embryology week 4 - 10

ASSOCIATIONS

  • Due to complex nature of development, LC are associated with other malformations
  • GI 16-67%
    • esophageal atresia, tracheoesophagealfistula, imperforate anus, intestinal malrotation
  • Genitourinary 14-44%
    • hypospadias, kidney malformations, inguinal hernia
  • Cardiac 16-33%
    • aortic coarctation, transposition of the great vessels, patent ductus arteriosus, and septal defects
  • Craniofacial 5-15%
    • cleft lip and palate, micrognathia, glossoptosis, microtia, hypertelorism, and choanalatresia
  • Respiratory 2-9%
    • tracheal and bronchial size and shape irregularities, stenosis

 

  • Opitz–Frias syndrome
  • Pallister-Hall syndrome
  • DiGeorgesyndrome
  • CHARGE syndrome
  • VACTERL association

OPITZ-FRIAS SYNDROME

  • X-linked or autosomal dominant
  • 1:4,000 to 1:100,000
  • 22q11.2 microdeletionsyndrome
  • facial anomalies
    • hypertelorismand broad nasal bridge, prominent forehead, antevertednares, cleft lip and/or palate
  • laryngotracheoesophagealdefects
  • genitourinary abnormalities
    • hypospadias, cryptorchidism, and hypoplastic/bifid scrotum
  • congenital heart defects, imperforate or ectopic anus, and midline brain defects

PALLISTER-HALL SYNDROME

  • autosomal dominant
  • prevalence unknown
  • GL13 gene mutation
  • extremity anomalies
    • polydactyly, syndactyly
  • hypothalamic hamartoma (tuber cinereumhamartoma)
  • bifid epiglottis or laryngeal cleft
  • imperforate anus and kidney abnormalities

 Pallister hall

DIGEORGESYNDROME

  • AKA velocardiofacialsyndrome, Shprintzensyndrome, CATCH22
  • autosomal dominant
  • 1:4,000
  • Cardiac abnormality
    • tetralogy of Fallot, VSD, persistent truncus arteriosus
  • Abnormal facies
    • hypertelorism, retro/micrognathia, long face, narrow palpebral fissures, small teeth, low-set ears, short philtrum, downturned mouth
  • Thymicaplasia
  • Cleft palate or VPI
  • Hypocalcemia/Hypoparathyroidism
  • 22q11.2 deletion
  • laryngotrachealanomalies

Laryngeal cleft CATCH 22

CHARGE SYNDROME

  • 1:10,000
  • CHD7 gene
  • Colobomaof the eye
  • Heart defects
  • Atresia of the choanae
  • Retardation of growth and/or development
  • Genital and/or urinaryabnormalities
  • Ear abnormalities and deafness.

laryngeal cleft charge syndrome 1laryngeal cleft charge syndrome 2

MAJOR CHARACTERISTICS OF CHARGE SYNDROME

Laryngeal cleft major characteristics of charge syndrome

Laryngeal cleft major characteristics of charge syndrome

VACTERLSYNDROME

  • 1:10,000 to 40,000
  • sporadic
  • Vertebral anomalies—hypoplasticvertebrae or hemivertebrae, scoliosis
  • Anal atresia
  • Cardiac anomalies—VSD, ASD, tetralogy of Fallot
  • TracheoEsophagealfistulas (TEF)
  • Renal anomalies
  • Limb anomalies—displaced or hypoplasticthumb, polydactyly, syndactyly, radial aplasia

TRACHEOESOPHAGEALFISTULA

  • incidence is 1:3,500 to 5,000 births
  • several classification systems
  • most commonly cited is Gross 1953
    • describes five types of TEF and EA

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ASSOCIATION BETWEEN LCAND TEF

  • Fraga, 2014
    • Retrospective chart review of 183 patients with LC
  • 161 patients with LC alone and 22 with LC and TEF
    • 11 patients with type I cleft
    • 9 patients with type II cleft
    • 2 patients with type III
    • 13 male, 9 female patients
    • 19 patients with EAand distal TEF
    • 3 patients with H-type fistula
    • 9 patients with VACTERL association, 1 patient with duodenal atresia

 

  • Evans—44 patients with LC, 12 with associated TEF/EA (27%)
  • Glossop—10 patients with LC, 2 with associated TEF/EA (20%)
  • Cohen—7 patients with LC, 4 with associated TEF/EA (57%)
  • Fraga—183 patients with LC, 22 with associated TEF/EA (12%)

 

  • LC and TEF group
    • 17 patients (77%) required repair of LC
    • 5patients (23%) responded to conservative tx
    • mean age of cleft repair was 4.69 years (58 months–17.83 years)

 

  • LC alone group
    • 134 patients (83%) required repair of LC
    • 27 patients (17%) responded to conservative tx
    • mean age at repair was 3.70 years (4 months–19.9 years)

 

  • confounders of TEF that can cause aspiration
    • LC
    • neuromuscular dyscoordination
    • vocal fold immobility from iatrogenic RLN injury
    • recurrent TEF
    • stricture
  • “We should not delay endoscopic airway examination in children with aspiration who also have a history of TEF repair.”

SIGNS AND SYMPTOMS

  • Varied presentation from no symptoms to acute respiratory failure.
  • Generally the severity of the symptoms correlates with the severity of the cleft.
  • 25% of type I LCs are asymptomatic.
    • stridor
    • aspiration
    • recurrent pneumonia
    • chronic lung disease
    • dysphagia
    • hoarseness
    • choking
    • chronic cough
    • failure to thrive
    • cyanosis
    • regurgitation/reflux

DIFFERENTIAL DIAGNOSIS

  • laryngomalacia
  • vocal cord paralysis
  • laryngopharyngeal reflux disease
  • neuromuscular swallowing disorder
  • reactive airway disease

WORKUP

  • History
  • Physical examination
    • FFL
    • FEES
  • Imagin
    • airway films
    • CXR
    • MBS

WORKUP—AIRWAY FILMS

  

WORKUP—CXR

WORKUP—MBS

 

  • cumulative radiation
  • provides little in the way of detailed laryngeal anatomy
  • only evaluates a few cycles
  • potential false negative if patient only aspirates intermittently
  • shows global swallowing mechanism
  • can provide prognostic information

WORKUP—FEES

 

  • provides dynamic view of laryngeal function and better anatomical analysis
  • limited use in the pediatric population
  • age one to four years least likely to be compliant

DIAGNOSIS

  • Associated findings:
    • narrowed inter-arytenoid distance
    • paramedianposition of the vocal folds
    • inter-arytenoid erythema
    • tracheal cobblestoning
  • Bronchoscopy also performed
  • Can take aspirates of tracheal secretions
    • measure lipid-laden macrophage index (LLMI) and neutrophil percentage

MEDICAL MANAGEMENT

Goals:

  • maintain optimal respiration
  • prevent pulmonary complication
  • esensure adequate nutrition

Treatment:

  • antirefluxtherapy
  • thickened liquid regimen
  • proper positioning during feeding
  • treat reactive airway disease
  • allow 6 month period before re-evaluation
    • monitor symptoms
    • monitor infections
  • improvement is result of patient growth and conditioning

MEDICAL MANAGEMENT

SURGICAL MANAGEMENT

  • injection laryngoplasty
  • endoscopic repair
  • open repair
  • robotic-assisted repair

INJECTION

Injection of material such as Gelfoaminto the laryngeal cleft to increase the vertical height of the inter arytenoid mucosa

ENDOSCOPIC

Endoscopic repair has become standard of care for type I and II clefts that fail medical management

  • Johnston—17 of 24 (71%) type I clefts, 14 of 17 (82%) type II clefts
  • Evans –13 of 16 (81%) type I and II clefts
  • Chien—15 of 16 (94%) type I clefts
  • Garabedian—4 of 4 (100%) type I and II clefts

OPEN

Open surgical techniques (anterior laryngofissureor lateral pharyngotomy) with possible thoracotomy or sternotomy

 

  • goal of repair of type III and IV clefts is to recreate separate tracheal and esophageal lumens
  • two suture lines and a greater chance for anastomotic leak compared with a single suture line
  • interposition grafts allow for stronger closure—pericardium, sternocleidomastoid muscle flaps, pleura, strap muscle, jejunum, and tibialperiosteum

ROBOTIC-ASSISTED

  • miniaturization of instrumentation
  • advantages
    • three-dimensional visualization, increased range of instrument movement, and filtration of tremor
  • disadvantages
    • longer operating times, high initial cost, specific training
  • 5 patients with type I cleft
    • 3 male, 2 female
    • average age at surgery was 21 months (15-29 months)
  • 100% patients had 4 weeks postoperative swallow testing show complete resolution of penetration and aspiration for all consistencies

 

REFERENCES

  • Fragaet al. The association between laryngeal cleft and tracheoesophagealfistula: Myth or reality? Laryngoscope 2014; 10.1002/24804
  • Jefferson et al. Low inter-arytenoid height: a subclassificationof type I laryngeal cleft diagnosis and management. IntJ PediatrOtorhiniolaryngol. 2015 Jan; 79(1):31-5.
  • Johnston et al. Laryngeal cleft: Evaluation and management. International Journal of Pediatric Otorhinolaryngology 78:(2014) 905–911.
  • Leboulangeret al. Laryngo-tracheo-oesophagealclefts. OrphanetJ Rare Dis. 2011 Dec 7;6:81.
  • Ojhaet al. Type I laryngeal cleft: a multidimensional management algorithm. JAMA OtolaryngolHead Neck Surg. 2014 Jan; 140(1):34-40.
  • Pansky. Development of The Lower Respiratory System: Larynx And Trachea. Review of Medical Embryology.
  • van der Doefet al. Clinical aspects of type I posterior laryngeal clefts: literature review and report of 31 patients. Laryngoscope. 2007 May;117(5):859-63.