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  • Test code: 01740
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae Weaver Syndrome Test

Test description

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.

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Primary panel (1 gene)

EZH2

  • EZH2-related overgrowth
  • Weaver syndrome
    • Weaver-Smith syndrome

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:

  • tall stature (reported in >90% of affected individuals)
  • intellectual disability—variable and frequently mild (reported in ~80% of affected individuals)

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:

Assay and technical information

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
EZH2 NM_004456.4