Choanal atresia

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Jaspinder Kaur, MBBS[2]

Synonyms and keywords: Atresia, Choanal; Atresias, Choanal; Choanal Atresias; Bosma arhinia microphthalmia syndrome; Bosma Henkin Christiansen syndrome; Congenital absence of nose and anterior nasopharynx (OMIM: 603457)

Overview

The word “Choana” is derivative of a greek word “Xovan” which states the funnel and hence, the term “Posterior Choana” is known as posterior nasal aperture or posterior funnel. Choanal atresia (CA) is the most common form of congenital nasal airway abnormality which presents with variable clinical features ranging from acute airway obstruction to chronic recurrent sinusitis depending upon the degree of obstruction. It is caused by the abnormal rupturing of the buccopharyngeal or naso-buccal membrane which results in the failed recanalization of the nasal fossae during the embryological period and hence, occlude the posterior nasal cavity to communicate with the nasopharynx. CA presents with severe respiratory distress, difficulty feeding, and failure to thrive when the obstruction is bilateral; and chronic persistent nasal discharge in unilateral cases. Establishing an airway is an acute otolaryngological emergency because newborns are obligate nasal breathers and experiences the paradoxical cyanosis episodes while feeding. The diagnosis requires a high index of suspicion and usually initial clinical evaluation done by introduction of a six or eight Fr suction catheter via the nostrils, methylene blue dye test, cotton wisp test, and laryngeal mirror test. The obstruction may be further visualized with a narrow flexible nasopharyngoscope after the nasal cavity has been suctioned of mucus and the nasal mucosa has been constricted with a nasal decongestant (e.g., oxymetazoline). However, the final confirmation of the diagnosis is done by CT scan of the nasal cavity which will demonstrate the atresia, define the type of tissue (bony or membranous), and show the configuration of the entire nasal cavity. The treatment of choanal atresia is essentially surgical which can be divided into emergent and elective definitive categories. It may be successfully treated by removing the obstructing tissue by using the nasal endoscopic approach via transnasal route. However, when the thick bony plate extremely narrows posterior nasal cavity, a transpalatal repair technique is more direct. An intraoperative topical application of mitomycin to inhibit fibroblast proliferation has shown to be an effective adjunct to the surgical repair of choanal atresia. Stents fashioned from endotracheal tubes are placed and secured alongwith sutures to the septum in order to prevent postoperative re-stenosis chances which are removed after 6 weeks of duration. The stents must be moistened with saline and suctioned several times daily to prevent mucus plugging and acute respiratory distress.

Historical Perspective

• 1755: Johann Roderer noticed total obstruction of the posterior nasal choana while examining a newborn and hence was the first to describe the CA.
• 1829: Oto et al. further characterized the CA anomalies in relation to the deformity of the palatine bones during an autopsy.
• 1854: Carl Emmert was the first to use the curved trochar through the choanal obstruction in transnasal surgical repair of bilateral CA in a 7- year-old boy and thus, successfully corrected CA surgically.
• 1880: Ronaldson described an importance of CA in his autopsy findings of the newborns who had died from asphyxia and acute respiratory distress.
• 1979: Hall first reports the “CHARGE” syndrome association in 17 children with multiple congenital anomalies who were ascertained by CA. In the same year, Hittner et al found the same syndrome in 10 children with ocular colobomas and multiple congenital anomalies, hence coined the syndrome as “Hall-Hittner syndrome”.
• 1981: Pagon et al. first elaborated the acronym "CHARGE" association (Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness).
• 1985: Dehaen conducted the first transnasal endoscopic repair of CA.
• 2008: Barbero et al found the association of CA with the maternal use of an antithyroid drug methimazole.

Classification

CA can be classified on the basis of several variables such as morphology, laterality, association with congenital anomalies and surrounding structures involvement.

Based on the morphology: The atretic plate has a thickness of usually 4-6 mm which attaches 1 to 2 mm anteriorly to the posterior border of hard palate.

Type of morphology	Past report (1910)	Recent data based on CT and histologic specimens (1996)
Membranous	10%	0%
Bony	90%	30%
Mixed membranous and bony atresia	0%	70%

Based on the laterality:

Characteristics features	Unilateral	Bilateral
Type of obstruction	Partial or one nasal passage blocked	Total or both nasal passages blocked
Incidence	70%	30%
Side: Right or left	Right (70%)	Both
Severity	Carries low morbidity	Life threatening
Onset of symptoms	Immediately after birth	Appears later in childhood or adulthood

Based on association with other congenital anomalies:

Characteristics features	Associated with other anomalies	No associations
Incidence	50%	50%
Type of CA	Bilateral CA	Unilateral CA
Syndromes associated	CHARGE syndrome, 9p monosomy, Crouzon syndrome, Marshall-Smith syndrome	None

Based on structure involvement:

Characteristics features	Membranous	Bony
Surrounding structural abnormalities	Failure of the bucconasal membrane to rupture between the 5th and 6th weeks of fetal development.	Medial thickening of the medial pterygoid plates; Lateral thickening of the posterior vomer; Narrow nasal cavity

Embryology

Origin: Development of the nasal cavity starts with neural crest cells migration from their origin in the dorsal neural folds and hence, the development of choanae takes place between the 4th and 11th weeks of gestation.

Gestational week	Developmental process
3rd and 4th week	Neural crest cells commence their caudal migration to reach the midface by the 4th week of gestation. The nasal processes or placodes on the lateral surface of head invaginate to form the nasal pits.
5th week	The nasal pits begin to fold inwards into the mesenchyme forming nasal sacs. These primitive nasal sacs are separated from oral cavity by oronasal membrane.
8th week	The oronasal membrane ruptures creating nasal cavity and a primitive choana located at the junction of nasal cavities and nasopharynx. During this phase of development, there is gradual proliferation of neural crest cells which contribute to the formation of skull base and nasal vaults. The lateral palatal shelves fuse in an anterior-to-posterior direction which forms the hard and soft palate.
10th week	The nasal septum and developing palate fuse. The primitive choanae gets pushed posteriorly and forms “Secondary choanae”. In normal fetus, these secondary choanae are patent for a functioning airway between the anterior nasal cavity and nasopharynx.

• Normal anatomical relations of the atretic plate in patients with CA are as follows:

1. Superior surface: Under surface of body of sphenoid
2. Lateral border: Medial pterygoid lamina
3. Medial border: Vomer
4. Inferior surface: Horizontal plate of palatine bone

Pathophysiology

• Obligate nose breathers: In neonates, the epiglottis is more superiorly placed as compared to adult so when infant swallows, the larynx rises above epiglottis position and touch the nasopharynx and locks between soft palate and side of nasopharynx. Due to the elevated laryngeal position compared to the adult counterpart, newborns are obligate nose breathers until mouth breathing is established with the descent of the larynx approximately 4–6 weeks of life.
• During inspiration, the neonate sucks the tongue and the vacuum is created in the oropharynx which helps to move soft tissue of the floor of mouth up and back towards soft palate.
• During expiration the pressure in the airway causes soft palate to push forward against the soft tissue and tongue in the mouth, which further obstructs the oral airway [8].
• Interrelation of respiration, feeding and crying episodes:
  • As the infants are obligate nasal breather, the oral airway is invariably blocked or used by them during normal respiration. Oral breathing is used by them only during crying.
  • The 1/3rd reduction in the diameter of the nasal airway increase nasal airway resistance by 81 times resulting in severe distress in neonates. As a result, the infant with bilateral CA experiences episodes of asphyxia and severe distress in quiet respiration when its mouth is closed, especially during periods of sleep or during feeding.
  • Feeding difficulty can be the initial alerting event in which the infants can present with progressive airway obstruction and choke episodes during feeding because of their inability to breathe and feed at the same time.
  • Moreover, the infant can become cyanotic which is relieved by crying or gasping when the child opens the mouth widely, releasing the air obstruction and the cyanosis disappears. If the crying stops, the mouth closes and the cycle repeats itself.
  • Similarly, as the child falls asleep the mouth closes and a progressive obstruction starts with stridor followed by increased respiratory effort and cyanosis. Either the observer opens the child's mouth or the child cries and the obstruction is cleared.
  • In resting state, child has severe retractions, and struggles to breath with rapid development of cyanosis. The infant with bilateral choanal atresia develops rarely an ability to breathe through mouth and hence, the medical emergency would exist in complete absence of patent both nasal cavities.

• Hengerer and Strome attributed the CA embryological foundations to four factors which try to explain the embryological origin of congenital CA.

1. Persistence of buccalpharyngeal membrane of anterior intestine;
2. Failure of Hochstetter bucconasal membrane to rupture which usually occurs in the seventh gestational week;
3. Abnormal adherence of the mesodermal tissue in the choanal region;
4. Abnormal guidance of mesodermal flow secondary to local factors.

• Other not so widely accepted theories are:

1. Resorption of secondary nasal fossa floor
2. Incomplete extension of nasal cavity dorsally
3. Migration of dorsal part of fronto nasal process to fuse with the palatal shelves

• However, none of these proposed pathologies gives a precise explanation for obstruction or minimization of the size of the choanal openings by developmental processes, and currently, there has been no definitive evidence supporting one theory over the others.

• Anatomical deformitites associated with CA includes:

1. The bony atretic plate is situated in front of the posterior bony septum
2. Nasal cavity is narrowed
3. Lateral pterygoid plates are found to be thickened compromising the nasal airway
4. Medially vomer is thickened
5. The membranous plate lies in between lateral pterygoid and vomer
6. High arched palate is common in these patients

Etiology

The exact cause of this anomaly is unknown but considered to be both genetic and environmental.

The Role of Retinoic Acid:

• Retinoic acid (RA) is produced from vitamin A by an enzyme retinaldehyde dehydrogenase (Raldh) which is important for ontogenesis and homeostasis of numerous tissues.
• However, studies have revealed that cranio facial anamolies with mesenchymal damage and cell disruption were reported among mothers with an ingestion of high doses of vitamin A during gestation period. It has been attributed to disturbances in migration pattern of neural crest cells which further led to the disturbances in mesoderm development in the cranio facial area.
• Dupe et al.: Using a mouse model, they demonstrated that Raldh3 knockout suppressed RA synthesis and caused CA via following proposed mechanisms:

1. Over-expression of fibroblast growth factor 8 (FGF-8),
2. Persistence of nasal fins whose rupture normally allowed the communication between nasal and oral cavities

• They further demonstrated that the CA in the Raldh knockout mice could be prevented by maternal treatment of RA.
• The role of FGF-8 in CA development was supported by the observation of prevalent CA among patients with craniosynostosis syndromes as a result of the elevated level of FGF-8 expression.

The Role of Thioamides:

• Thioamides: Methimazole, carbimazole, and propylthiouracil, are commonly used as medical treatment for hyperthyroidism.
• Several case reports have been published demonstrating the potential association of CA in the newborns whose mothers had prenatal use of thioamides for their thyroid hyperfunctioning.
• Moreover, Barbero et al. conducted a case- control study which further supported the relation of prenatal exposure to maternal hyperthyroidism treated with methimazole with CA development.
• Methimazole crosses the placenta and enters the fetal circulation which in turn reduces the T4 levels of the fetus. Therefore, infants born with CA have shown a marked decrease in their T4 levels.
• Teratogenic syndromes causing bilateral CA includes:

1. Methimazole embryopathy
2. Carbimazole embryopathy

• However, it is not completely supported because of lack of significant evidences.
• Maternal Hyperthyroidism: Although, based on the thorough study of case reports and critical literature reviews, it was stated that the mother’s hyperthyroidism rather than the methimazole treatment might be the causal factor for CA.
• Elevated thyroid-stimulating hormones (TSH) level was associated with increased level of FGF, FGF receptor, and other proliferating growth factors, which hypothetically form the basis for CA development.
• Hence, further studies are required to further delineate the causes and pathogenesis of CA.

Excessive Coffee Intake: Excessive consumption of coffee in the form of more than 3 cups/day increases the chances of CA by interrupting the membrane rupture which leads to an outgrowth of palate towards the medial side and further blocks the communication between the nasal cavities and the pharynx [21].

Genetics:

• Familial cases: About 8% (Gorlin, 1982).
• Multifactorial trait: The fact is supported by both affected successive generations and affected single generations (Lang, 1912; Phelps, 1926; McGovern, 1950).
• CHARGE syndrome: The abnormalities in the CHD7 gene have been identified in 64% of patients diagnosed with CHARGE, and hence, allowing screening of the gene for patients with CA and other related anomalies. However, the exact function of the CHD7 gene is largely unknown.

Differentiating Choanal atresia from other Diseases

Following conditions must be ruled out in any neonates, infant or child presented with acute or frequent episodes of nasal or upper airway obstruction.

Conditions mimicking Choanal Atresia
Antrochoanal polyp Chordoma Deviated nasal septum Dislocated nasal septum Hematoma Isolated piriform aperture stenosis Nasal dermoid Nasal harmatoma Nasal haemangioma Nasal cerebral heterotopia (glioma) Nasolacrimal duct cyst Encephaloceles: the encephaloceles can be frontonasal, frontoethmoidal or frontosphenoidal Turbinate hypertrophy

Epidemiology and Demographics

• “Rule of 2:1” states the ratio of unilateral to bilateral CA, female to male and the right sided to the left sided CA.
• The incidence is 1:5,000 to 1:8,000 per live-born children.
• Although its incidence is rare, it represents the most common congenital abnormality of the nose.
• Maternal age and parity does not affect the frequency of this congenital anomaly.
• Slightly increased risk exists in twin pregnancy.
• It is observed with equal frequency among all races and hence, no racial or ethnic preference is seen.

Risk Factors

• The relation of risk factors and its implications is always complex. A risk factor increases the predisposition towards a disease in comparison to an individual with no risk factors. However, some risk factors are more important than others; hence, acquiring a single or multiple risk factor does not mean that one will develop the disorder. Moreover, absence of a risk factor does not guarantee the disease free state.
• 2010: An epidemiological report found higher associations between increased incidence of CA and exposure to second-hand-smoke, coffee consumption, high maternal zinc and B-12 intake and exposure to anti-infective urinary tract medications.
• 2012: Another epidemiological study studied “atrazine” a commonly used herbicide in the U.S. used to treat agricultural crops, and found that women who lived in counties in Texas with the highest levels of this chemical being were 80 times more likely to give birth to neonates with CA in relation to women who lived in the counties with its lowest levels.
• To sum up, the risk factors for the development of Choanal Atresia are following listed:

1. Exposure to chemicals (atrazine) and medications (methimazole) that act as endocrine disrupters during gestation.
2. Exposure to secondhand smoke during gestational period.
3. Excessive consumption of coffee by pregnant mothers exposes the developing fetus to caffeine
4. Elevated levels of vitamin B-12 and zinc in a pregnant woman exposes the fetus to the same
5. Multiple pregnancies, such as twins, carries a higher risk
6. Presence of certain congenital disorders that are associated with Choanal Atresia including Crouzon syndrome, Antley-Bixler syndrome, and Pfeiffer syndrome further increase its chances of development.

Screening

When neonate/infant/child presented with a nasal/upper airway obstruction or respiratory distress, CA must be screened with other differential diagnosis and anomalies.

Diagnosis

History and Symptoms | Physical Examination | Laboratory Findings | Chest X Ray | CT | MRI | Other Imaging Findings | Other Diagnostic Studies

Presentation

It can be unilateral or bilateral.

Sometimes, a unilateral choanal atresia is not detected until much later in life because the baby manages to get along with only one nostril available for breathing.

Bilateral choanal atresia is a very serious life-threatening condition because the baby will then be unable to breathe directly after birth as babies are obligate nasal breathers (they must use their noses to breathe). These babies usually require airway resuscitation right after birth.

Treatment

The only possible treatment is surgery to correct the defect.

See also

• CHARGE syndrome
• choana

References

Template:Congenital malformations and deformations of respiratory system

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