CHARGE Syndrome

A life-threatening, congenital syndrome of multiple abnormalities, consisting of coloboma, heart disease, choanal atresia, mental and growth retardation, genital and urinary anomalies, and ear anomalies with deafness. The prognosis worsens if the disorder is associated with concomitant cyanotic congenital heart disease, central nervous system anomalies, and esophageal atresia. CHARGE is an acronym for coloboma, heart anomaly, choanal atresia, mental and growth retardation, genital anomalies, and ear anomalies.

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CHARGE Association.

Approximately 1:13,000-15,000 live births. No sexual or racial predilection has been reported.

More than 90% of the cases occur sporadically. Exposure to teratogenic substances (e.g., thalidomide, hydantoin), but also maternal diabetes mellitus have been suggested to play a causative role. The residual cases are familial with autosomal recessive transmission.

CHARGE syndrome is a midline developmental defect attributed to an arrest in embryologic differentiation during early organogenesis. The mechanism has not been precisely identified, but may include failure of the cervical neural crest cells to migrate into the derivatives of the pharyngeal pouches and arches, deficient blastogenesis as a result of defective interaction between mesoderm and neural crest cells, and failure of mesoderm formation.

None of the features in the CHARGE acronym are universally present. The clinical diagnosis is based on the presence of four of the seven features described in the acronym, including at least one major anomaly. Patients may present in the neonatal period with respiratory distress and feeding difficulties. Delayed presentation is usually associated with persistent nasal discharge, failure to thrive, audiovisual defects, and developmental delay.

Prenatal ultrasound may already reveal polyhydramnios, intrauterine growth retardation, and brain and heart anomalies. A wide range of features involve the heart (present in up to 80% of patients; cardiac defects such as atrial and ventricular septal defects, atrioventricular canal, conotruncal malformations, tetralogy of Fallot, hypoplastic left heart syndrome, patent ductus arteriosus, pulmonary stenosis, and coarctation of the aorta are common), the airway (choanal atresia is bilateral in 50% of cases and may present with respiratory distress in the neonatal period when bilateral; choanal stenosis is less common; laryngomalacia, laryngeal cleft, and subglottic stenosis are occasionally seen), the central nervous system (mild-to-moderate mental retardation is common; seizures are occasionally present; multiple cranial neuropathies such as facial nerve palsy, sensorineural hearing loss [the most common feature in CHARGE syndrome], glossopharyngeal and vagal nerve palsy with swallowing problems resulting in frequent aspirations, and hyposmia may be present; magnetic resonance imaging of the brain usually demonstrates cerebral atrophy, midline brain defects, forebrain anomalies, and occasionally hydrocephalus), the genitourinary system (vesicoureteral reflux, hydronephrosis, horseshoe kidney, absent kidney, genital hypoplasia [micropenis, hypospadias, cryptorchidism]), and the skeleton (hypotonia of the upper truncus, hemivertebrae, scoliosis, clinodactyly, and syndactyly). Tracheoesophageal fistula and esophageal atresia are present occasionally (in up to 20% of patients). Facial abnormalities may include a square face with asymmetry, dysplasia of the external and middle ear (Mondini defect), midface hypoplasia and micrognathia, nerve palsies, and cleft lip/palate, but usually are mild. Heart defects and postoperative pulmonary complications are the major cause of death.

The presence of active lower respiratory tract infections should be determined and treated preoperatively. Renal function should be assessed (creatinine and blood urea nitrogen). Cardiac function and anatomy should be defined preoperatively by echocardiography. Check for seizure activity (electroencephalography). Prolonged postoperative mechanical ventilation may be required (laryngomalacia, frequent aspirations, truncal hypotonia). Preoperative and postoperative chest physiotherapy is often helpful. Because of mental retardation and hearing loss, cooperation may be limited. Sedative and/or anxiolytic premedication and the presence of the primary caregiver during induction of anesthesia may be helpful.

The presence of midface hypoplasia, micrognathia, anterior larynx, small mouth, and cleft lip and palate may make face-mask ventilation and tracheal intubation difficult. Airway management seems to become more difficult with age. Laryngomalacia may require continuous positive airway pressure when a face mask is used. A smaller than expected tube size may be needed in the presence of subglottic stenosis. From an airway point of view, spontaneous ventilation should be maintained until the airway has been secured. However, because these patients have an increased risk of aspiration (even in the absence of a tracheoesophageal fistula), a rapid-sequence induction is preferable. The decision regarding priority (airway management vs. aspiration) depends on the clinical findings and patient history. Choanal atresia makes nasogastric tube and nasal airway management impossible. Special management is required in the presence of congenital cardiac lesions. Careful intraoperative positioning is needed.

Muscle relaxants should be avoided until the airway has been secured. Subacute bacterial endocarditis prophylaxis may be needed, depending on the cardiac defect and the kind of procedure to be done. Chronic antiseizure medication may alter metabolism and elimination of some anesthetic drugs.

DiGeorge Syndrome: A genetic defect leading to a wide range of phenotypic presentations, mainly developmental defects in the outflow tract of the heart, hypoparathyroidism with hypocalcemia, and thymic hypoplasia/aplasia with immune defects.

Renal-Coloboma Syndrome: A familial syndrome combining ocular, renal, and neurologic anomalies.

Velocardiofacial Syndrome: Includes typical facies and cardiac anomalies. Various other malformations can be associated (including endocrine and ophthalmic structures). It is a phenotypical variant of the DiGeorge syndrome.

VA(C)TER(L) Association: The acronym describes vertebral anomalies, anal atresia, (cardiac defects), tracheo-esophageal fistula, renal anomalies and limb anomalies. Other coexisting abnormalities must be excluded.