The Invitae CHARGE Syndrome Test analyzes CHD7, a gene that is associated with CHARGE syndrome, a multisystemic disorder present at birth. The constellation of findings may differ significantly between individuals with this disorder. Many of the minor symptoms associated with CHARGE syndrome are common in individuals who do not have the disorder; in those cases, genetic testing can be helpful to confirm or rule out a diagnosis.
Identification of a genetic cause of symptoms that may be related to CHARGE syndrome can impact medical management, provide a predicted outcome for the patient, and indicate the recurrence risk. A quick and definitive diagnosis is important for these patients because newborns with CHARGE syndrome may have several life-threatening medical problems and would require prompt evaluation of various systems, including airway function, heart function, and feeding.
The Invitae Isolated and Syndromic Congenital Heart Disease Panel has been designed to provide a broad genetic analysis of congenital heart disease. It may be considered as an alternative to testing for specific disorders. Depending on the individual’s clinical and family history, this broader panel may be appropriate. It can be ordered at no additional charge.
CHARGE syndrome is a multisystemic disorder that presents at birth. CHARGE is an acronym for the major symptoms of the disorder: coloboma, heart defect, atresia choanae (choanal atresia), retarded growth and development, genital abnormalities, and ear anomalies. Coloboma, or a hole in the eye, is a common feature of CHARGE syndrome. It may be present in one or both eyes and can cause vision impairment. Individuals with CHARGE syndrome often present with multiple acute medical conditions in the neonatal period.
Affected individuals may also present with cranial nerve abnormalities leading to swallowing problems and facial paralysis. Feeding difficulties are a major cause of morbidity. Other symptoms may include cleft lip or cleft palate, a fistula connecting the esophagus and the trachea (tracheoesophagal fistula), and distinctive facial features. CHARGE syndrome has a variable clinical presentation; not all affected individuals will present with all of the symptoms described above.
CHD7 is the only gene that is currently known to be associated with CHARGE syndrome. A pathogenic variant in this gene is present in approximately 65%-70% of individuals who have either a clinical diagnosis of CHARGE syndrome or at least three major features.
CHARGE syndrome is inherited in an autosomal dominant pattern. The majority of cases are de novo, although parent-to-child transmissions and germline mosaicism have been reported.
Current data show that 100% of individuals with a CHD7 variant related to CHARGE syndrome will have at least some features of the syndrome. Signs of CHARGE syndrome begin during fetal development and are present at birth. CHARGE syndrome shows extremely variable expressivity, even within the same family.
CHARGE syndrome has a prevalence of approximately 1 in 10,000 live births. A Canadian study reported an incidence of 1 in 8,500.
Genetic testing can be helpful for patients with minor features of CHARGE syndrome which are not specific to the disorder. Many of the minor features of the syndrome are common in individuals who do not have CHARGE syndrome and genetic testing allows for a more accurate diagnosis in those cases.
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, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
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|