CHARGE Syndrome

CHARGE syndrome (CS) is an autosomal dominant genetic condition caused by a mutation in the CHD7 gene. The incidence is approximately 1 in 10,000 to 15,000 live births. Most cases result from de novo mutations on the q12 arm of chromosome 8, which interfere with neural crest cell migration and embryogenesis. The parent of a child with a de novo mutation causing CS has a recurrence risk of approximately 1% to 3% for future pregnancies. However, if the disease-causing mutation of the proband is found in a parent, depending upon whether in a mosaic or nonmosaic form, the recurrence risk may be increased up to 50%, and subsequent pregnancies can be screened genetically and with fetal ultrasonography and/or magnetic resonance imaging.

CS remains a predominantly clinical diagnosis that can be confirmed with genetic testing. Physical features are highly variable and include those represented by the CHARGE mnemonic: Coloboma ocular, Heart defects, Atresia or stenosis of the choanae, Retardation of growth and/or development, Genitourinary anomalies, and Ear abnormalities. However, the mnemonic does not include all of the major diagnostic criteria. Central nervous system findings are important clues to the diagnosis, with more than 90% of affected individuals having cranial nerve (CN) dysfunction. Many individuals have more than 1 dysfunctional cranial nerve, manifesting as an absent or reduced sense of smell (CN I), weak chewing/swallowing (CN V), facial palsy (CN VII) (Fig 1), sensorineural hearing loss (CN VIII), balance vestibular problems (CN VIII), and swallowing problems (CN IX, X). Visual and hearing impairments as well as intellectual disabilities are prevalent and can range …