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Cornelia de Lange Syndrome via the HDAC8 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
HDAC8 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
15245HDAC881479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Stela Berisha, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Cornelia de Lange syndrome (CdLS) is characterized by distinctive facial features, growth retardation, hirsutism, and upper limb reduction defects that range from subtle phalangeal abnormalities to oligodactyly. Craniofacial features include synophrys, arched eyebrows, long eyelashes, small upturned nose, small widely spaced teeth, and microcephaly. IQ ranges from below 30 to 102 (mean: 53). Many individuals demonstrate autistic and self-destructive tendencies. Frequent findings include cardiac septal defects, gastrointestinal dysfunction, hearing loss, myopia, and cryptorchidism or hypoplastic genitalia. Individuals with a milder phenotype have less severe growth, cognitive, and limb involvement, but often have facial features consistent with CdLS (Deardorff et al. GeneReview, 2011).


CdLS can be caused by mutations in NIPBL, SMC1A, SMC3, RAD21 and HDAC8. HDAC8-related Cornelia de Lange syndrome (OMIM#300882) is inherited in an X-linked manner. Female carriers may show symptoms depending on X-inactivation (Mannini, L. et al. Hum Mutat Aug 29, 2013. [Epub ahead of print]). HDAC8 protein (Histone deacetylase 8 protein) coded by HDAC8, is an enzyme in the histone deacetylase family and plays a key role in transcriptional regulation by affecting the acetylation state of core histones in the nucleus of cells. It is also involved in the deacetylation of cohesin complex protein SMC3, regulating release of cohesin complexes from chromatin (Buggy, J.J. et al. Biochem J 350(1):199-205, 2000; Deardorff, M.A. et al. Nature 489(7415):313-317, 2012). To date, five mutations (four missense, 1 nonsense) have been found in patients with Cornelia de Lange syndrome and a splicing mutation has been found in a large Dutch family with intellectual disability, truncal obesity, gynaecomastia, hypogonadism and unusual facial features. Some of these features overlap with Wilson-Turner syndrome (OMIM#309585) (Harakalova, M. et al. J Med Genet 49(8): 539-543, 2012).

Clinical Sensitivity - Sequencing with CNV PG-Select

One study identified HDAC8 mutations in five out of 154 individuals affected with CdLS syndrome without NIPBL mutations (Deardorff, M.A. et al. Nature 489(7415):313-317, 2012).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the HDAC8 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients with symptoms consistent with Cornelia de Lange Syndrome, particularly with a family pattern consistent with X-linked inheritance, and the family members of patients who have known HDAC8 mutations.


Official Gene Symbol OMIM ID
HDAC8 300269
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Cornelia de Lange syndrome 5 XL 300882
Wilson-Turner syndrome XL 309585


  • Buggy, J.J. et al. (2000). "Cloning and characterization of a novel human histone deacetylase, HDAC8" Biochem J 350 Pt 1:199-205. PubMed ID: 10926844
  • Deardorff MA, Bando M, Nakato R, Watrin E, Itoh T, Minamino M, Saitoh K, Komata M, Katou Y, Clark D, Cole KE, Baere E De, et al. 2012. HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle. Nature 489: 313–317. PubMed ID: 22885700
  • Deardorff, M.A. et al.  2011. Cornelia de Lange Syndrome. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301283
  • Harakalova, M. et al. (2012). “X-exome sequencing identifies a HDAC8 variant in a large pedigree with X-linked intellectual disability, truncal obesity, gynaecomastia, hypogonadism and unusual face.”  J Med Genet 49(8): 539-543. PubMed ID: 22889856
  • Mannini L, Cucco F, Quarantotti V, Krantz ID, Musio A. 2013. Mutation Spectrum and Genotype-Phenotype Correlation in Cornelia de Lange Syndrome. Human Mutation 34: 1589–1596. PubMed ID: 24038889


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

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2) Select Additional Test Options

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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