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), ...