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