• Test code: 04727
  • 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

Invitae Cornelia de Lange Syndrome Panel

Test description

The Invitae Cornelia de Lange Syndrome Panel analyzes up to seven genes associated with Cornelia de Lange syndrome (CdLS), a multiple-congenital-malformation disorder. These genes were selected based on the available evidence to date to provide Invitae’s broadest test for Cornelia de Lange Syndrome.

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.

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Primary panel (6 genes)


Add-on Preliminary-evidence Gene for Cornelia de Lange Syndrome (1 gene)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include a gene which does not currently have a definitive clinical association, but which may prove to be clinically significant in the future. This gene can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more. The EP300 gene is also associated with autosomal dominant Rubinstein-Taybi syndrome (PMID: 24352918).


  • Cornelia de Lange Syndrome (CdLS)
    • classic CdLS
    • mild CdLS

Cornelia de Lange syndrome (CdLS) is a multiple congenital malformation disorder with a broad spectrum of clinical involvement including characteristic facial features, gastrointestinal disease, growth restriction, intellectual disability, and malformations of the limbs, diaphragm, and cardiac, gastrointestinal, and musculoskeletal systems. Neurodevelopmental findings include developmental delays, anxiety, and depression, as well as obsessive-compulsive, self-injurious, and autistic behaviors. CdLS may present as the more severe classic CdLS subtype or the less severe mild CdLS subtype.

Variants in NIPBL, SMC1A, and SMC3 account for approximately 65% of cases of CdLS.

NIPBL, RAD21, SMC and EP300-related CdLS are inherited in an autosomal dominant manner. HDAC8 and SMC1A-related CdLS are inherited in an X-linked dominant pattern. The majority of CdLS occurs due to de novo mutations. Somatic and germline mosaicism have been reported.

Both NIPBL- and SMC1A-related forms of CdLS are highly penetrant. The penetrance for SMC3-, RAD21-, and HDAC8-related CdLS is not well-established.

Prevalence of CdLS has most recently been estimated at 1 in 50,000; however, the prevalence may be underestimated due to underdiagnosis of the mild subtype of CdLS.

This panel may be appropriate to confirm a diagnosis in an individual who meets clinical criteria for classic CdLS or to establish a diagnosis in an individual who is suspected to have mild CdLS.

  1. Kline, AD, et al. Cornelia de Lange syndrome: clinical review, diagnostic and scoring systems, and anticipatory guidance. Am. J. Med. Genet. A. 2007; 143A(12):1287-96. PMID: 17508425
  2. Musio, A, et al. X-linked Cornelia de Lange syndrome owing to SMC1L1 mutations. Nat. Genet. 2006; 38(5):528-30. PMID: 16604071
  3. Deardorff, MA, et al. Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation. Am. J. Hum. Genet. 2007; 80(3):485-94. PMID: 17273969
  4. Deardorff, MA, et al. Cornelia de Lange Syndrome. 2005 Sep 16. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301283
  5. Liu, J, Krantz, ID. Cornelia de Lange syndrome, cohesin, and beyond. Clin. Genet. 2009; 76(4):303-14. PMID: 19793304
  6. Niu, DM, et al. Paternal gonadal mosaicism of NIPBL mutation in a father of siblings with Cornelia de Lange syndrome. Prenat. Diagn. 2006; 26(11):1054-7. PMID: 16958143
  7. Borck, G, et al. Father-to-daughter transmission of Cornelia de Lange syndrome caused by a mutation in the 5' untranslated region of the NIPBL Gene. Hum. Mutat. 2006; 27(8):731-5. PMID: 16799922
  8. Ansari, M, et al. Genetic heterogeneity in Cornelia de Lange syndrome (CdLS) and CdLS-like phenotypes with observed and predicted levels of mosaicism. J. Med. Genet. 2014; 51(10):659-68. PMID: 25125236
  9. Barisic, I, et al. Descriptive epidemiology of Cornelia de Lange syndrome in Europe. Am. J. Med. Genet. A. 2008; 146A(1):51-9. PMID: 18074387
  10. Woods, SA, et al. Exome sequencing identifies a novel EP300 frame shift mutation in a patient with features that overlap Cornelia de Lange syndrome. Am. J. Med. Genet. A. 2014; 164A(1):251-8. PMID: 24352918
  11. Parenti, I, et al. Broadening of cohesinopathies: exome sequencing identifies mutations in ANKRD11 in two patients with Cornelia de Lange-overlapping phenotype. Clin. Genet. 2016; 89(1):74-81. PMID: 25652421

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 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
ANKRD11 NM_013275.5
EP300 NM_001429.3
HDAC8 NM_018486.2
NIPBL NM_133433.3
RAD21 NM_006265.2
SMC1A NM_006306.3
SMC3 NM_005445.3