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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.
Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|