CHARGE Syndrome

Introduction

• The group of anomalies was first described in 1979 in patients with choanal atresia and other abnormalities.¹
• In 1981, the term “CHARGE association” was described using some of the features for the acronym Coloboma, Heart defect, Atresia choanae, Retarded growth, Genital hypoplasia, and Ear hypoplasia or deafness.^2,3
• The term “CHARGE syndrome” is used currently since most patients have been identified to have mutations within the CHD7 gene on chromosome 8q12.^2,3
• The incidence of CHARGE syndrome is estimated to range from 0.1-1.2/10,000 live births.²
• Most cases are due to de novo mutations in the CHD7 gene that occur sporadically.^2,3
• Autosomal dominant inheritance with variable expressivity has also been reported.
• A clinical diagnosis of typical CHARGE syndrome is when patients have three major criteria or two major and two minor criteria (Table 1).³

Clinical Presentation and Associated Anomalies

There is wide variation in the presentation of patients with CHARGE syndrome.

Colobomas^2,3

• Colobomas and other eye abnormalities are reported in the majority (75-90%) of patients.^2,3
• Colobomas are usually bilateral, and involve the eye lid, iris, retina, choroid, optic disc, or macula. The typical coloboma is chorioretinal and predisposes to retinal detachment and visual impairment (Figure 1).
• Vision may be normal or severely impaired.

Heart Defects^2,3

• They occur in 75-80% of patients with CHARGE syndrome.
• Conotruncal heart defects (tetralogy of Fallot, double-outlet right ventricle, interrupted aortic arch) and atrioventricular septal defects are common.

Choanal Atresia/Airway anomalies^2,3

• Choanal atresia is present in about 65% of patients.
• It may be unilateral or bilateral and can be membranous or bony.
• Bilateral choanal atresia presents at birth with respiratory distress or cyanosis as infants are obligate nasal breathers. Symptoms improve with crying.
• Airway obstruction is present in about 70% of patients: laryngomalacia (40%), tracheomalacia (20%), and subglottic stenosis (10%).
• Cleft lip and palate are seen in about 15-20% of patients.
• Tracheoesophageal fistula is seen in about 15-20% of patients.
• Obstructive sleep apnea is present in about 65% of patients.⁴

Growth and Developmental Retardation^2,3

• Growth retardation results in short stature and pubertal delay.
• Cognitive impairment is common with low intelligence quotient that is less than 70 in over 70% of patients. This often results in communication and language delay.

Genitourinary Problems^2,3

• Genital hypoplasia is common with cryptorchidism and micropenis in males and hypoplastic labia and clitoris in females.
• Delayed puberty or pubertal arrest is common.

Ear and Hearing Problems^2,3

• Ear anomalies are reported in 85-100% of patients.
• The characteristic external ear appearance is a wide, low set, and cup-shaped ear with a hypoplastic lobule. A triangular concha is a common finding (Figure 2).
• The most common inner ear abnormality is the absence of the lateral semicircular canals.
• Both conductive and sensorineural hearing loss is common.

Cranial Nerve Anomalies

• Cranial nerve (CN) dysfunctions include the CN I (anosmia in almost all patients), CN VII (facial palsy), CN VIII (sensorineural hearing loss), and CN IX/X/XI (feeding and swallowing issues, velopharyngeal insufficiency).
• Conditions with similar or overlapping elements include VACTERL association, 22q11 deletion syndrome, and oculo-auriculo-vertebral spectrum.^2,3

Preanesthetic Evaluation

• Many features of CHARGE require anesthesia for diagnostic or surgical interventions during childhood.
• Most patients will require surgery within the first two months of life.⁵

• A multidisciplinary consultation with general pediatrics, medical genetics, otolaryngology, cardiology, and ophthalmology should be considered to guide evaluation.³
• History
  • Prior surgeries, anesthetics, and intubations
  • Developmental stage, coping skills, cooperation (if considering awake intubation)
• Physical exam
  • Perform detailed airway evaluation
  • Evaluate for lower respiratory signs of chronic aspiration or pneumonia
  • Evaluate for cardiac murmurs
• Imaging
  • Echocardiogram

Anesthetic Considerations and Management

• Anticipate challenges with communication and cooperation and consider premedication (Table 3).
• Subacute bacterial endocarditis prophylaxis may be indicated.
• An increased risk of aspiration due to reflux and secretion intolerance may be present.
• Micrognathia increases the risk of difficulty with intubation.⁶
• Laryngomalacia places CHARGE patients at an increased risk of obstruction due to upper airway collapse during anesthesia.⁶ Patients may require increased positive end-expiratory pressure with mask ventilation or when using a supraglottic airway.
• Postoperative adverse airway events are common in patients with CHARGE syndrome.⁵
• Consider combining procedures under a single anesthetic.

Emergence

• Neuromuscular blockade should be reversed.
• Secretions should be carefully suctioned given swallowing dysfunction.
• Close monitoring should be ensured during recovery from anesthesia due to risks of airway events.