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by Margaret A. Hefner and Sandra L. H. Davenport
Although CHARGE syndrome is a genetic condition most often caused by mutations in the CHD7 gene (see Genetic Diagnosis, p. 40), the diagnosis is still clinical, based on the presence of specific major and minor characteristics. Beyond the major and minor diagnostic characteristics are many additional findings in CHARGE that may be critically important in management.
Major characteristics are ocular coloboma, choanal atresia, cranial nerve abnormalities (anosmia, facial palsy, severe suck and swallow incoordination), and characteristic ears (outer ear shape, ossicular anomalies and eustachian tube dysfunction, cochlear and/or semicircular canal abnormalities). The most common features in CHARGE are cochlear and semicircular canal anomalies, which are found in >90% of children with CHARGE when imaged by MRI. Minor characteristics are those which are common in CHARGE syndrome, but are either less specific to CHARGE (e.g., heart defects), or more difficult to evaluate consistently (e.g., characteristic CHARGE syndrome face). Minor characteristics are congenital heart defects, genital hypoplasia, renal anomalies, tracheo-esophageal fistula/esophageal atresia, cleft lip or palate, growth retardation, and characteristic face and hands.
Occasional findings in CHARGE syndrome are features which may not be diagnostic by themselves, but which support a diagnosis of CHARGE and may be important in management. These include DiGeorge sequence in the absence of 22q11.2 deletion, omphalocele or umbilical hernia, bony scoliosis or hemivertebrae and additional dysmorphic features (thumb or limb anomalies, short webbed neck with sloping shoulders, nipple anomalies). If a diagnosis of CHARGE syndrome is being considered in an older individual, the typical CHARGE behavioral profile may be helpful as well. Many other syndromes (especially 22q deletion syndrome and some chromosome abnormalities) have features which overlap with CHARGE. Diagnosis of CHARGE syndrome should be made by a medical geneticist familiar with CHARGE.
Children with CHARGE syndrome show marked delays in motor development due to vestibular dysfunction in combination with prolonged hospitalization, truncal hypotonia with ligamentous laxity, decreased visual acuity and hearing impairment. Many children are reluctant to crawl, often moving by scooting in a combat crawl, pushing with their feet in the supine position or using a five-point crawl (head down). The average age of walking is 3-4 years. Language development is delayed due to multiple sensory deficits, motor deficits, and delay in establishment of an appropriate communication system.
Although developmental delays might be expected in children with CHARGE syndrome, the incidence of cognitive impairment in CHARGE syndrome is probably 50% or less. Factors which correlate with better apparent development in the teen years include age of walking and degree of visual impairment. Some children with CHARGE syndrome have specific learning disabilities such as difficulty understanding math. Many adults with CHARGE syndrome live independently and several are college graduates.
Margaret A. Hefner is a clinical associate professor in the Department of Medical Genetics, Department of Pediatrics at Saint Louis University School of Medicine.
Sandra L. H. Davenport is a pediatric geneticist and developmental pediatrician in Bloomington, MN. She works with the Minnesota Deaf-Blind Project.
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