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 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|