The Invitae Oculo-Facio-Cardio-Dental Syndrome Test analyzes BCOR, which is the gene that is associated with oculo-facio-cardio-dental syndrome (OFCD). OFCD is characterized by ocular, facial, dental, and cardiac anomalies and affects only females. Clinical diagnosis can be challenging due to the wide variety of symptoms and the rarity of the disorder; genetic testing may provide a definitive diagnosis. Mutations in the BCOR gene also cause Lenz microphthalmia (LMS). Loss-of-function mutations in BCOR are associated with OFCD, but only a single missense mutation, p.Pro85Leu, has been identified in patients with LMS.
Identifying a genetic cause of symptoms that may be related to OFCD or LMS can impact medical management, provide a predicted outcome for the patient, and indicate the recurrence risk.
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 broader panel can be ordered at no additional charge.
Oculo-facio-cardio-dental (OFCD) syndrome is a multisystemic condition that affects the development of the eyes, face, heart, and teeth in females.
BCOR is the only gene that is currently associated with OFCD. The percentage of individuals with OFCD who have a pathogenic change in BCOR is unknown.
OFCD is inherited in an X-linked dominant pattern and is lethal in males. LMS is inherited in an X-linked recessive pattern.
Penetrance of OFCD is unknown. Radiculomegaly of the canines is the most consistent finding among patients. There is extreme variable expressivity, even in the same family. Dental and ocular abnormalities occur more frequently than those involving the facial and cardiac systems. Part of this variability may be a result of skewed X-inactivation. Some features of the condition, such as heart defects and dental anomalies, manifest early in development; other features, such as cataracts and vision impairment, may not develop until later in life.
OFCD is extremely rare. Incidence is estimated at fewer than 1 in 1,000,000.
The rarity and variable expressivity of this disorder makes clinical diagnosis challenging. Genetic testing can diagnose or rule out OFCD in individuals with an ambiguous clinical presentation. Genetic testing should be considered for individuals presenting with radiculomegaly.
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|