The Invitae van der Woude Syndrome Panel analyzes two genes that are associated with van der Woude syndrome (VDWS), a congenital disorder characterized by cleft lip or cleft palate and by bilateral paramedian lower lip pits. These genes were selected based on the available evidence to date.
Genetic testing of these genes may confirm a diagnosis and help guide medical management. Identification of a disease-causing variant can also inform recurrence-risk assessment and genetic counseling.
Van der Woude syndrome (VDWS) is a congenital disorder that is characterized by cleft lip or cleft palate and by bilateral paramedian lower lip pits. Other associated features may include small mounds of tissue on the lower lip, hypodontia, ankyloglossia, limb abnormalities, hearing loss, and congenital heart defects.
Pathogenic variants in the IRF6 gene account for up to 80% of VDWS. A pathogenic variant in GRHL3 is found in approximately 17% of individuals who have clinical features of VDWS but do not have a pathogenic variant in IRF6.
VDWS is inherited in an autosomal dominant manner and exhibits clinical variability.
VDWS exhibits reduced penetrance and variable expression. Approximately 86%–92% of patients with pathogenic variants in IRF6 or GRHL3 meet clinical diagnostic criteria for VDWS.
VDWS is the single most common cause of cleft lip and cleft palate, accounting for 2% of cases. Prevalence is estimated at 1 in 35,000 to 100,000.
Genetic testing may establish or confirm a diagnosis in individuals suspected of having van der Woude syndrome (VDWS). Testing may be appropriate for individuals with or without a family history of any combination of the following features: lip pits, cleft lip with or without cleft palate, isolated cleft palate, and submucous cleft palate.
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|