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.