CHARGE Syndrome: CHD7 Gene Deletion/Duplication

Condition Description

CHARGE is a mnemonic that stands for coloboma, heart defects, choanal atresia, retarded growth and development, genital abnormalities, and ear anomalies. 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.

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Genes (1)

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Indications

This test is indicated for:

  • Confirmation of a clinical diagnosis of CHARGE syndrome in individuals who have tested negative for sequence analysis

Methodology

DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.

Detection

Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient's clinical and/or biochemical phenotype.

Specimen Requirements

When sample fails to meet the acceptable criteria, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (eglgc@egl-eurofins.com).
Submit only 1 of the following specimen types
Whole Blood (EDTA)
WBP

Requirements
EDTA (Purple Top)
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
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 24 hours of collection. Do not refrigerate or freeze.
DNA, Isolated
DNA

Requirements
Microtainer
3µg
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.

Special Instructions

Submit copies of diagnostic biochemical test results with the sample, if appropriate. Contact the laboratory if further information is needed.

Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of EGL Genetics, please submit a copy of the sequencing report with the test requisition.

  • Sequence analysis of the CHD7 gene is available and is required before deletion/duplication analysis.
  • Prenatal testing is available to couples who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.

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