This test analyzes EZH2, which is the gene that is most commonly associated with Weaver syndrome. This condition is an overgrowth syndrome and is characterized by tall stature, cognitive delays, distinctive facies, skeletal findings (advanced bone age and camptodactyly of the fingers or toes), and variable other findings.
Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
Weaver syndrome is an overgrowth syndrome and is characterized by tall stature, cognitive delays, distinctive facies (retrognathia, broad forehead, widely spaced eyes, almond-shaped palpebral fissures), skeletal findings (advanced bone age and camptodactyly of the fingers or toes), and variable other findings. Some individuals with germline mutations in EZH2 have only presented with tall stature. Individuals with Weaver syndrome may have an increased risk of developing cancer, but due to the rarity of Weaver syndrome, the exact risk of developing tumors is difficult to determine.
Due to the rarity of Weaver syndrome, the lifetime risk of developing specific tumors is unknown, but a small number of affected individuals has been reported to have acute lymphoblastic leukemia (ALL), neuroblastoma, and non-Hodgkins lymphoma (NHL).
Weaver syndrome has an autosomal dominant mode of inheritance. The majority of cases are due to de novo mutations.
The prevalence of Weaver syndrome is currently unknown. Approximately 50 cases have been reported in the literature.
Clinical diagnosis of Weaver syndrome can be challenging because features are variable and nonspecific. Many of these features are present during infancy and early childhood, but later resolve; for this reason, they may be missed if detailed infant and early-childhood photographs and histories are unavailable.
Common features include:
More specific but less-frequently manifested characteristics include camptodactyly, soft, doughy skin, umbilical hernia, and a low, hoarse cry (reported in 30%–50% of affected individuals).
Further details regarding the features associated with Weaver syndrome can be found at:
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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.
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|
EZH2: Sequencing analysis for exons 20 includes only cds +/- 10 bp.