Beckwith-Wiedemann Syndrome via the CDKN1C 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
10005 CDKN1C 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
10005CDKN1C81479 81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

Targeted Testing

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

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder characterized by macrosomia, macroglossia (large tongue), visceromegaly, embryonal tumors (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma), omphalocele, neonatal hypoglycemia, ear creases/pits, adrenocortical cytomegaly, and renal abnormalities (e.g., medullary dysplasia, nephrocalcinosis, medullary sponge kidney, and nephromegaly; Shuman et al. GeneReviews. 2010). BWS shows clinical heterogeneity and suspicion should arise if only a few of the clinical features are present. Individuals with BWS are also known to have somatic mosacism. For example, they can show hemihyperplasia. Early diagnosis is important, because children can have life threatening hypoglycemia and early-onset cancers. The prevalence of BWS is 1 in 13,700 livebirths (Choufani et al. American Journal of Medical Genetics Part C (Seminars in Medical Genetics)154C:343–354, 2010).

Genetics

Beckwith-Wiedemann syndrome is caused by defects in imprinting at the chromosomal location 11p15. Approximately 50% of BWS cases are the result of loss of maternal methylation, 20% due to paternal uniparental disomy, and 5% are the result of an imprinting center variant on the maternal chromosomal location 11p15. In addition, variants in CDKN1C can be found in 40% of familial BWS cases and 5-10% of sporadic BWS cases. CDKN1C, a putative tumor suppressor gene that negatively regulates cellular proliferation and a putative negative regulator of fetal growth, is a maternally expressed gene (Choufani et al. American Journal of Medical Genetics Part C (Seminars in Medical Genetics) 154C:343–354, 2010). Variants in CDKN1C are inherited in an autosomal dominant manner. Most variants reported to date include missense variants; however, nonsense, missense, splice site, small insertions and deletions, and large duplications have also been described.

Testing Strategy

This test provides full coverage of all coding exons of the CDKN1C gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Clinical Sensitivity - Sequencing with CNV PG-Select

CDKN1C variants can be found in 40% of familial BWS cases and 5-10% of non-familial BWS cases. This sequencing test will not detect any imprinting defects that cause BWS.

Indications for Test

Candidates for this test include patients suspected to have Beckwith-Wiedemann syndrome who have no methylation defects at chromosome 11p15 or individuals who have a family history of Beckwith-Wiedemann syndrome. Individuals who have BWS with cleft palate or neuroblastoma are also known to have CDKN1C variants (Li et al. Genomics 74:370–6, 2001; Alsultan et al. Pediatr Blood Cancer 51:695–8 2008). CDKN1C variants have also recently been reported in patients with IMAGe syndrome (intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies), which is an undergrowth developmental disorder (Arboleda et al. Nat Genet 2012 May 27. doi: 10.1038/ng.2275). This test is specifically designed for heritable germline variants and is not appropriate for the detection of somatic variants in tumor tissue.

Gene

Official Gene Symbol OMIM ID
CDKN1C 600856
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Beckwith-Wiedemann Syndrome AD 130650

Related Test

Name
Cancer Panel

Citations

  • Alsultan et al. (2008). "Simultaneous occurrence of right adrenocortical tumor and left adrenal neuroblastoma in an infant with Beckwith-Wiedemann syndrome.." Pediatr Blood Cancer 51:695–8. PubMed ID: 18668518
  • Arboleda et al. (2012). "Mutations in the PCNA-binding domain of CDKN1C cause IMAGe syndrome." Nat Genet May 27. doi: 10.1038/ng.2275. PubMed ID: 22634751
  • Choufani et al. (2010). "Beckwith-Wiedemann syndrome.." American Journal of Medical Genetics Part C (Seminars in Medical Genetics) 154C:343–354. PubMed ID: 20803657
  • Li et al. (2001). "Imprinting status of 11p15 genes in Beckwith-Wiedemann syndrome patients with CDKN1C mutations.." Genomics 74:370–6. PubMed ID: 11414765
  • Shuman et al. GeneReviews. 2010
  • Shuman et al. GeneReviews. 2010

Ordering/Specimens

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.

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


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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