DNA icon

Hennekam Lymphangiectasia-Lymphedema Syndrome via the CCBE1 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
CCBE1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11143CCBE181479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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


  • Siwu Peng, PhD

Clinical Features and Genetics

Clinical Features

Primary lymphedema is a chronic condition that arises from an abnormality of the lymphatic system. Hennekam syndrome (OMIM 235510) is a type of primary lymphedema characterized by severe lymphedema in the limbs, genitalia, and face, complicated by facial dysmorphism and mental retardation (Hennekam et al. Am J Med Genet 34:593-600, 1989). Facial features vary, but are typically characterized by a flattened face and nasal bridge, hypertelorism, epicanthal folds, small mouth, tooth anomalies, and ear defects accompanied by hearing loss. Lymphedema is progressive, often beginning in utero with hydrops fetalis and can be asymmetrical (Van Balkom et al. Am J Med Genet 112:412-421, 2002). Edema is typically accompanied by hypoproteinemia and immunologic abnormalities, such as hypogammaglobulinemia and lymphocytopenia. Angiectasias of lymph vessels in the intestines and other organs (e.g. pleura pericardium, thyroid, and kidneys) are a hallmark of Hennekam syndrome (Hennekam et al. Am J Med Genet 34:593-600, 1989; Alders et al. Nat Genet 41:1272-1274, 2009). Additional features may include congenital heart defects, pyloric stenosis, glaucoma, hypothyroidism, camptodactyly, rectal prolapse, and renal anomalies (Angle and Hersh. Am J Med Genet 71:211-214, 1997; Van Balkom et al. Am J Med Genet 112:412-421, 2002; Al-Gazali et al. Clin Dysmorphol 12:227-232, 2003; Bellini et al. Am J Med Genet 120A:92-96, 2003).


Phenotypic abnormalities arise due to impaired prenatal and postnatal lymphatic flow resulting from insufficient CCBE1 gene function during lymphangiogenesis. The CCBE1 protein plays a direct role in lymphatic vessel formation and venous sprouting. Variants throughout the CCBE1 gene have been identified as causes of Hennekam syndrome (Hennekam et al. Am J Med Genet 34:593-600, 1989; Hogan et al. Nat Genet 41:396-398, 2009; Connell et al. Hum Genet 127:231-241, 2010). Details of the molecular mechanism of the CCBE1 protein function remain incomplete; however, it is speculated that CCBE1 may be a component of the extracellular matrix involved in guidance of migrating cells during lymphangiogenesis (Hogan et al. Nat Genet 41:396-398, 2009). Variants in the CCBE1 gene are inherited in an autosomal recessive manner and comprise primarily missense and nonsense variants. No predominant CCBE1 variants have been identified to date.

Clinical Sensitivity - Sequencing with CNV PGxome

Sensitivity of this test is unknown.

Testing Strategy

This test provides full coverage of all coding exons of the CCBE1 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. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Patients with clinical features of Hennekam syndrome or a family history of lymphedema, and patients with lymphedema that test negative for variants in the FLT4 and FOXC2 genes. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CCBE1.


Official Gene Symbol OMIM ID
CCBE1 612753
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Hennekam Syndrome AR 235510


  • Al-Gazali LI, Hertecant J, Ahmed R, Khan NA, Padmanabhan R. 2003. Further delineation of Hennekam syndrome. Clinical Dysmorphology 12: 227–232. PubMed ID: 14564208
  • Alders M, Hogan BM, Gjini E, Salehi F, Al-Gazali L, Hennekam EA, Holmberg EE, Mannens MMAM, Mulder MF, Offerhaus GJA, Prescott TE, Schroor EJ, et al. 2009. Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans. Nature Genetics 41: 1272–1274. PubMed ID: 19935664
  • Angle B, Hersh JH. 1997. Expansion of the phenotype in Hennekam syndrome: a case with new manifestations. Am. J. Med. Genet. 71: 211–214. PubMed ID: 9217224
  • Balkom IDC Van, Alders M, Allanson J, Bellini C, Frank U, Jong G De, Kolbe I, Lacombe D, Rockson S, Rowe P, Wijburg F, Hennekam RCM. 2002. Lymphedema-lymphangiectasia-mental retardation (Hennekam) syndrome: A review. American Journal of Medical Genetics 112: 412–421. PubMed ID: 12376947
  • Bellini C, Mazzella M, Arioni C, Campisi C, Taddei G, Tomΰ P, Boccardo F, Hennekam RC, Serra G. 2003. Hennekam syndrome presenting as nonimmune hydrops fetalis, congenital chylothorax, and congenital pulmonary lymphangiectasia. Am. J. Med. Genet. A 120A: 92–96. PubMed ID: 12794699
  • Connell, F., et.al. (2010). "Linkage and sequence analysis indicate that CCBE1 is mutated in recessively inherited generalised lymphatic dysplasia." Hum Genet 127(2): 231-41. PubMed ID: 19911200
  • Hennekam RCM, Geerdink RA, Hamel BCJ, Hennekam FAM, Kraus P, Rammeloo JA, Tillemans AAW. 1989. Autosomal recessive intestinal lymphangiectasia and lymphedema, with facial anomalies and mental retardation. American journal of medical genetics 34: 593–600. PubMed ID: 2624276
  • Hogan, B. M., et.al. (2009). "Ccbe1 is required for embryonic lymphangiogenesis and venous sprouting." Nat Genet 41(4): 396-8. PubMed ID: 19287381


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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

loading Loading... ×


An error has occurred while calculating the price. Please try again or contact us for assistance.

View Ordering Instructions

1) Select Test Method (Platform)

1) Select Test Type

2) Select Additional Test Options

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: loading
Patient Prompt Pay Price: loading
A patient prompt pay discount is available if payment is made by the patient and received prior to the time of reporting.
Show Patient Prompt Pay Price
Copy Text to Clipboard