In most cases, CHARGE syndrome is due to heterozygous mutations in CHD7 (8q12.2) encoding the chromodomain helicase DNA-binding protein. Patients may manifest an autistic like behavior associated with attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD) and anxiety. severe combined immune deficiencies, isolated T-cell lymphopenia) are also observed. Endocrine dysfunction (growth hormone deficiency, hypogonadotropic hypogonadism) and immune abnormalities (e.g. congenital laryngomalacia, congenital tracheomalacia see these terms), tracheoesophageal fistula (TEF) and gastroesophageal reflux are common. Dysmorphic facial features include square face, prominent forehead, prominent nasal bridge and asymmetry from the facial palsy. Motor delay (due to balance problems), speech delay and delay in fine motor skills are also noted. Failure to thrive is often related to the severe sucking/swallowing problems. Genital hypoplasia and delayed puberty are observed. Central nervous system (CNS) defects involve cerebral atrophy, corpus callosum agenesis, posterior fossa anomalies and cerebellar hypoplasia. Cranial nerve abnormalities are frequent and include abnormalities of the olfactory, facial, auditory, vestibular nerves and those involved in swallowing. Ear anomalies (95-100%) include low-set lop or cup-shaped outer ear with deficient cartilage of the outer pinna and a triangular concha, middle ear ossicle malformations, leading to chronic serous otitis media, and sensorineural hearing loss. Coloboma, more likely retinal, is present in 75-90% and can be in conjunction with microphthalmia and lead to vision loss. conotruncal heart malformations, aortic arch defects see these terms). It presents in the neonatal period with cyanosis due to choanal atresia (60-70%, bony/membranous, unilateral/bilateral) and/or cyanotic heart disease (75-80% e.g. The syndrome shows a variable clinical picture, even within a family, depending on the associated anomalies. The incidence is estimated to be 1/12,000 - 15,000 live births.