CHARGEis a mnemonic that stands for coloboma, heart defects, choanal atresia, retarded growth and development, genital abnormalities, and earanomalies. CHARGE syndrome is characterized by unilateral or bilateral coloboma of the iris, retina-choroid, and/or disc with or without microphthalmos (80%-90% of individuals); unilateral or bilateral choanal atresia or stenosis (50%-60%); cranial nerve dysfunction resulting in hyposomia or anosmia,unilateral or bilateral facial palsy (40%), impaired hearing, and/or swallowing problems (70%-90%); abnormal outer ears, ossicular malformations, Mondini defect of the cochlea, and absent or hypoplastic semicircular canals; cryptorchidism in males and hypogonadotrophic hypogonadism in both males and females; developmental delay; cardiovascular malformations (75%-85%); growth deficiency (70%-80%); orofacial clefts (15%-20%); and tracheoesophageal fistula (15%-20%). Neonates with CHARGE syndrome often have multiple life-threatening medical conditions. Feeding difficulties are a major cause of morbidity in all age groups.
The diagnosis of CHARGE syndrome is based on clinical findings and temporal bone imaging. The CHD7 gene (8q12.1) is the only gene currently known to be associated with CHARGE syndrome; it encodes the chromodomain helicase DNA binding protein.Sequence analysis of the CHD7 coding region detects mutations in approximately 60%-65% of individuals with CHARGE syndrome. While one study suggested that individuals with CHARGE syndrome caused by a mutation in CHD7 were more likely to exhibit cardiovascular malformations, coloboma of the eye, and facial asymmetry, another study found no genotype-phenotype correlations in this cohort and noted that there were differences in clinical presentation even in sib pairs with identical mutations. Most individuals diagnosed with CHARGE syndrome represent simplex cases (i.e., a single occurrence in a family), although CHARGE syndromecaused by mutation of CHD7 can be inherited in an autosomal dominant manner. CHARGE syndrome has an estimated birth incidence of 1 in 10-12,000
Mutationsin CHD7 have also been shown to cause Kallmann syndrome-5, an allelic disorderwith a less severe but overlapping phenotype. Patients with anosmia and/or hypogonadotropichypogonadism, therefore, should be screened for additional clinical features ofCHARGE syndrome.
Click here for the GeneTests summary on this condition.
This test is indicated for:
- Confirmation of a clinical/biochemical diagnosis of CHARGE syndrome
Clinical Sensitivity: 60-65%. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient''''s biochemical phenotype.
Analytical Sensitivity: ~99%
Orangene™ Saliva Collection Kit used according to manufacturer instructions. Please contact EGL for a Saliva Collection Kit for patients that cannot provide a blood sample.
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Submit copies of diagnostic biochemical test results with the sample, if appropriate. Contact the laboratory if further information is needed.
- Custom diagnostic mutation analysis (KM) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.
- Prenatal testing is available to individuals who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.