The Invitae Ellis-van Creveld and Weyers Acrofacial Dysostosis Panel analyzes two genes that are associated with Ellis-van Creveld syndrome (EvC) and Weyers acrofacial dysostosis (WAD) (also known as Weyers acrodental dysostosis), which are characterized by variable developmental defects involving the skeletal system, ectoderm, and cardiovascular system. These genes are the only genes associated with Ellis van Creveld syndrome and Weyers acrofacial dysostosis at this time.
Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant can inform recurrence-risk assessment and genetic counseling.
Ellis-van Creveld (EvC), also known as chondroectodermal dysplasia, is a syndrome characterized by variable developmental defects involving the skeletal system, ectoderm, and cardiovascular system. Features include disproportionate short stature, short ribs, postaxial polydactyly, dysplastic nails, oral anomalies, and cardiovascular malformations.
Weyers acrofacial dysostosis (WAD), also known as Weyers acrodental dysostosis, has similar features to those found in EvC including postaxial polydactyly of hands and feet, dental abnormalities, and nail dystrophy; however, the clinical presentation is typically milder than what is reported in EvC.
In studies of individuals with Ellis-van Creveld syndrome 31-63% had variants identified in EVC and 22-38% had variants identified in EVC2.
To date the EVC and EVC2 genes are the only genes associated with Weyers acrofacial dysostosis, however, data is insufficient to determine the clinical sensitivity of sequencing and duplication/deletion analysis of these two genes.
Ellis-van Creveld syndrome is inherited in an autosomal recessive pattern. Weyers acrofacial dysostosis is inherited in an autosomal dominant pattern.
Penetrance of Ellis-van Creveld syndrome is high while penetrance of Weyers acrofacial dysostosis is unknown.
Ellis-van Creveld syndrome (EvC) and Weyers acrofacial dysostosis are rare conditions. The prevalence of EvC has been estimated at 1 in 60,000 – 143,000 births in the general population. EvC is most common in the Old Order Amish population of Lancaster, Pennsylvania, with a prevalence of 1 in 5,000 births.
The diagnosis of Ellis-van Creveld syndrome may be suspected in individuals with disproportionate short stature, short ribs, polydactyly, and oral anomalies including, but not limited to, multiple gingivolabial musculofibrous frenula, conical teeth, and occasional neonatal teeth.
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|