• Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit




Associated disorders

The CHD7 gene is associated with autosomal dominant CHARGE syndrome (MedGen UID: 75567) and Kallmann syndrome (MedGen UID: 102469).

The CHD7 gene encodes a chromodomain helicase DNA-binding protein, which regulates gene expression by chromatin remodeling and is essential for proper neural-crest formation during development.

OMIM: 608892

Clinical condition
The CHD7 gene is associated with autosomal dominant CHARGE syndrome, a highly variable disorder affecting many parts of the body with characteristic features, including ocular coloboma, heart defects, choanal atresia, retarded growth and development, genital abnormalities, and ear anomalies (PMID: 17299439, 21378379). The acronym CHARGE refers to a set of non-random congenital malformations: coloboma of the eye, heart malformation, atresia of the choanae, retarded growth and/or development, genital hypoplasia, and ear anomalies (PMID: 9545604).

More specifically, individuals with CHARGE syndrome tend to have bilateral ocular colobomas involving the chorioretina and optic nerve, which can result in visual field defects in the upper quadrant, refractive errors, severe myoptic astigmatism, anisometropia, microphthalmia, microcornea, and reduced visual acuity (PMID: 20186815). The heart defects associated with CHARGE include tetralogy of Fallot, patent ductus arteriosus, atrial septal defects, and solitary septal defects, all in varying combinations (PMID: 20186815). Choanal atresia is highly correlated with CHARGE and tends to be osseous and bilateral (PMID: 17299439). Other ear, nose, and throat anomalies include laryngeal cleft, subglottic stenosis, hyposmia, tracheomalacia, tracheoesophageal fistula, and cleft palate/lip (PMID: 20186815). Although choanal atresia is associated with CHARGE, it is not commonly found in conjunction with cleft palate (PMID: 16615981, 17299439). Growth defects include short stature and low birth weight (PMID: 16615981). Hypogonadotropic hypogonadism and delayed puberty can be seen in males, and hypoplasia of the uterus and labia can occur in females (PMID: 20186815). Hearing-related abnormalities associated with CHARGE include deafness, inner and external ear abnormalities, deficiency in at least one of the semicircular canals, and cochlear hypoplasia (PMID: 20186815, 16615981).

Pathogenic variants in CHD7 have been reported in individuals with Kallman syndrome, which is characterized by hypogonadotropic hypogonadism due to gonadotropin hormone deficiency and anosmia (impaired sense of smell; PMID: 16882753, 15001591). However, these individuals may also have additional features characteristic of CHARGE syndrome.

Due to the multiple life-threatening medical conditions present in individuals with CHARGE syndrome, infant mortality is high, and there is increased mortality and morbidity throughout childhood, adolescence, and adulthood (PMID: 20186815, 2317068, 29088501).

Gene information
The CHD7 gene encodes a chromodomain helicase DNA-binding protein, which regulates gene expression by chromatin remodeling and is essential for proper neural crest formation during embryonic development (PMID: 20130577, 20591827). More specifically, the CHD7-encoded protein binds to enhancer elements and assists in the process of chromatin looping, which ultimately impacts transcriptional regulation by bringing the enhancer closer to the transcription start sites (PMID: 20186815). The characteristic features found in CHARGE syndrome are likely caused by the dysregulation of CHD7-targeted genes, which are responsible for the proliferation, differentiation, and migration of developing cell types and tissues, including eye, ear, heart, and the olfactory system (PMID: 20186815). Loss-of-function variants in CHD7 are known to be pathogenic (PMID: 16400610, 22461308).

CHD7 exhibits autosomal dominant inheritance. This means that an individual with a pathogenic variant has a 50% chance of passing the variant on to their offspring. Most individuals with CHARGE syndrome harbor a de novo pathogenic variant. However, in rare cases, a pathogenic variant may be inherited from a mildly affected parent (PMID: 17299439). Germline mosaicism has also been reported (PMID: 19475719).

Medical management for patients with CHARGE is improved by coordinated multidisciplinary care (PMID: 9545604, 2317068). Focus may be often placed on more severe, life-threatening health issues; however, it is important not to overlook minor features when treating patients with CHARGE (PMID: 29168326). The proposed management guidelines for CHARGE include the following.


  • Referral to a pediatric ophthalmologist to determine presence and severity of coloboma; additional testing of visual fields can help determine other findings, including examination of the retina and optic disk, even if the patient does not have an iridal coloboma (PMID: 16615981, 28160409)
  • Ophthalmologic evaluations including dilated eye exam in infancy and annual vision check (PMID: 28160409)
  • Referral for cardiac evaluation to identify cardiovascular anomalies via echocardiogram and X-ray (PMID: 28160409)
    Ear, nose, and throat:
  • Evaluate for:
    • choanal atresia or stenosis via nasal endoscopy or CT scan (PMID: 15890414, 28160409)
    • cleft palate (PMID: 28160409)
    • inner ear, middle ear, temporal bone, and facial nerve malformations via head CT/MRI scan (PMID: 11241470, 16959034, 28160409)
  • Otoacoustic emissions and automated auditory brainstem response hearing tests to assess for cochlear implant, which can be used for hearing rehabilitation even in cases of severe inner ear anomalies (PMID: 28160409, 24125186)
  • Evaluation of swallowing function in standard otolaryngologic examination, including either a fiberoptic endoscopic evaluation of swallowing (FEES) or video swallow study (VSS) in addition to feeding team assessments (PMID: 15890414, 28160409)
  • Annual hearing tests are recommended (PMID: 28160409)
  • Pressure equalization tube placement for patients may be considered for recurrent otitis media (PMID: 28160409)
  • Complete blood count as well as differential and extended electrolyte panel to screen for lymphopenia and hypocalcemia (28160409)
  • Electroencephalogram if seizures are present (PMID: 28160409)
  • Identify cranial nerve problems, including absent sense of smell, facial nerve palsy, sensorineural hearing loss, and vertigo (PMID: 28160409)
  • Bladder and renal ultrasound; voiding cystourethrography to identify renal anomalies (PMID: 16959034, 9915472, 28160409)
  • Screening of gonadotropins performed by 3 months of age (PMID: 28160409)
  • If puberty has not occurred by 13-14 years of age, screen for hypogonadotropic hypogonadism (PMID: 10995509)
    Genetic counseling
  • Clinical genetics consultation to discuss reproductive risk associated with CHD7 pathogenic variants (PMID: 27739643)
  • Examine hips for dysplasia (PMID: 28160409)
  • Refer to physiotherapist and occupational therapist to assist with balance (PMID: 28160409)
  • Monitor for scoliosis (PMID: 28160409)
  • Recommend an individualized education plan and refer to a speech therapist to assist with articulation and communication (PMID: 28160409)

Review date: March 2018

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
CHD7 NM_017780.3