• Test Code:
    1245
  • Department:
  • Test Synonyms:
    CraniosynostosisAchondroplasiaAntley-Bixler syndromeApert syndromeBaller-Gerold syndromeCraniofrontonasal dysplasiaCraniosynostosis mental retardation syndrome of Lin and GettigCrouzon’s SyndromeBeare-Stevenson cutis gyrate syndromeHunter-McAlpine craniosynostosisJackson-Weiss syndromeMuenke syndromeOpitz trigonocephaly syndromePfeiffer syndromePierre Robin SyndromePOR (Cytochrome P450 Oxidoreductase) deficiency with Antley-Bixler phenotypeSaethre-Chotzen syndromeShprintzen-Goldberg craniosynostosis ALPLALX4ASXL1CDC45CYP26B1EFNB1ERFFBN1FGFR1FGFR2FGFR3FREM1GLI3IFT122IFT43IL11RAMASP1MSX2P4HBPORRAB23RECQL4SEC24DSKISLC25A24TGFBR1TGFBR2TMCO1TWIST1WDR19WDR35Z1C1
  • CPT Code(s):
    81408
Background:

Craniosynostosis is the premature fusion (closure) of one or more sutures of the skull. It is a developmental anomaly with age of onset in utero and infancy.  The early sutural closure often leads to abnormal head shape and facial dysmorphia.  Craniosynostosis can occur in isolation (nonsyndromic) or as part of a larger syndrome with additional facial, skeletal, and organ anomalies (syndromic).  There are approximately 200 syndromes associated with craniosynostosis.  Clinical phenotype indicating a syndromic cause of craniosynostosis include limb defects, ear and eye abnormalities, maxillary and mandibular hypoplasia, and or cardiovascular malformations.  It is a genetically heterogeneous disorder with mutations identified in multiple genes.  Inheritance is autosomal dominant and recessive depending on syndrome.  Chromosomal alterations are a causative mechanism of the syndromic forms of craniosynostosis in more than 10% of the cases. 

Reasons for Referral:

  • Patient displays craniofacial phenotype consistent with craniosynostosis
  • Radiography and CT reveal premature fusion of one or more cranial sutures.   Patient may one or more of the following:  Chiari malformations, facial dysmorphia and or asymmetry, ptosis, blepharophimosis, hypertelorism, proptosis, down slanting palpebral fissures, choanal atresia or stenosis, flat nasal bridge, midfacial hypoplasia, maxillary hypoplasia, micrognathia, mandibular prognathism,  oral abnormalities, radiohumeral synostosis, radioulnar synostosis, syndactyly of the fingers and toes, brachydactyly, broad halluces with medial deviation
  • Carrier testing
  • Positive family history

Methodology:

Next generation sequencing will analyze the exons or coding regions of 34 Craniosynostosis-associated genes using Illumina NextSeq 500 technology.  Samples are prepared using hybridization probes to enrich exonic regions.  Promoter, intronic, etc. regions are not assessed on our assay, but may contain variants that impact gene function.

The 34 Craniosynostosis-associated genes are listed below:
ALPL, ALX4, ASXL1, CDC45, CYP26B1, EFNB1, ERF, FBN1, FGFR1, FGFR2, FGFR3, FREM1, GLI3, IFT122, IFT43, IL11RA, MASP1, MEGF8, MSX2, P4HB, POR, RAB23, RECQL4, SEC24D, SKI, TCF12, TGFBR1, TGFBR2, TMCO1, TWIST1, WDR19, WDR35, ZIC1

Specimen Requirements:

Blood:  EDTA or ACD (Solution A or B):

  • Adult: 5 mL
  • Child: 5 mL
  • Infant: 2-3 mL

Saliva: 2 ORAgene™ Saliva Collection Kit(s) (OGR-500) used according to manufacturer instructions.  Please contact KDL Client Services for a Saliva Collection Kit for patients that cannot provide a blood sample.

DNA: 10 µg at a minimum of 60-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)

For routine testing of blood and saliva (or DNA extracted from them), KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion.  For extraordinary circumstances, where testing must be performed outside of the above windows, please contact our lab.

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Test Performed (Days):

Weekly

Turn Around Time:

8 weeks

Shipment Sensitivity Requirements:

  • Package and ship specimen to remain cold, but not frozen. 
  • Ship via overnight express, using the FedEx priority overnight label provided. 
  • Contact Client Services for shipping kits and instructions at (855) 535-1522.

References:

  1. Wilke AO, Bochukova EG, Hansen RM, et al.  Clinical dividends from the molecular genetic diagnosis of craniosynostosis.  Am J Med Genet A.  2007; 143A(16):1941-98
  2. Panigrahi I.  Craniosynostosis genetics: The mystery unfolds.  Indian J Hum Genet.  2011; 17(2):48-53
  3. Agochukwu NB, Solomon BD, Muenke M.  Impact of genetics on the diagnosis and clinical management of syndromic craniosynostosis.  Childs Nerv Syst.  2012;28(9):1447-63

Additional Info:

The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials.

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