• Test Code:
    1697
  • Department:
  • Test Synonyms:
    Ambiguous genitaliaBifid scrotumCryptorchidismGonadal dysgenesisHypogonadotropic hypogonadismHypospadiusMicropenisSex reversal
  • CPT Code(s):
    81173
Background:

Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, and phenotypic sex are discordant. This heterogeneous group of disorders have phenotypic variability and can be challenging to diagnose. This panel is designed to evaluate for individuals with isolated or syndromic disorders of sexual development, which can include ambiguous genitalia, genitourinary (GU) anomalies, gonadal dysgenesis, or hypogonadotropic hypogonadism.

Combining exon – level deletion/duplication data analyzed by microarray with sequence analysis by next generation sequencing data will allow KDL to improve diagnostic yield and deliver more comprehensive results.

The results from genetic tests can facilitate assessment of levels of risk for patients and lead to more efficient and appropriate medical management. It is recommended that this testing be accompanied by a complete family history and genetic counseling.

Reasons for Referral:

  • Molecular confirmation of a clinical diagnosis of DSD

  • To aid in decision-making for treatment and management of individuals with DSD.

Methodology:

Component 1: Next generation sequencing will analyze the exons or coding regions of 107 Disorders of Sexual Development-associated genes using Illumina NextSeq 500/550 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.

Component 2: A customized CytoSure “exon-centric” array (Oxford Gene Technology) will be used to detect deletions and duplications.  The targeted array has enhanced probes targeted to the exonic regions of 107 Disorders of Sexual Development-associated genes.  The arrays are run using Agilent SureScan technology.

The 107 Disorders of Sexual Development-associated genes are listed below:

AKR1C2, AKR1C4, AMH, AMHR2, AR, ARX, ATRX, BMP4, CBX2, CDKN1C, CEP41, CHD7, CREBBP, CUL7, CYB5A, CYP11A1, CYP11B1, CYP17A1, CYP19A1, CYP21A2, DHCR24, DHCR7, DHH, DYNC2H1, EFNB1, ESCO2, EVC, EVC2, FAM58A, FGF10, FGF8, FGFR1, FGFR3, FIG4, FLNA, FRAS1, FREM2, GATA4, GNRH1, GNRHR, GPC3, GRIP1, HCCS, HNF1B, HOXA13, HS6ST1, HSD17B3, HSD17B4, HSD3B2, ICK, INSL3, IRF6, KAL1 (aka ANOS1), KISS1R, LEP, LHB, LHCGR, MAMLD1, MAP3K1, MED12, MID1, MKKS, MKS1, NEK1, NR0B1 (DAX1), NR5A1, NSMF, OPHN1, PCNT, PDE4D, PEX1, PITX2, POR, PROK2, PROKR2, PTPN11, RBBP8, RIPK4, ROR2, RSPO1, SALL1, SEMA3A, SETBP1, SOX10, SOX2, SOX9, SPECC1L, SRD5A2, SRY, STAR, TACR3, TBX15, TMEM70, TP63, TRIM32, TSPYL1, TTC8, TWIST2, UBR1, WDR11, WDR35, WNT4, WNT5A, WNT7A, WT1, ZEB2, ZFPM2

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.

Skin Fibroblast: Punch Biopsy (Cell cultures will be prepared at KDL and used for testing), or 2 T-25 confluent flasks

Prenatal:

  • Direct Amniotic Fluid (10-20mL)

  • Direct CVS

  • Cultured Amnio or CVS (2-T25 flasks)

  • Cultured Fetal Tissue: Product of Conception (2-T25 flasks)

  • Cord Blood (1-2 mL)

DNA: 10µg 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)

Notice Regarding Molecular Genetic Testing on CVS or Amniotic Fluid Specimens:

  • Maternal cell rule-out testing will be performed on all prenatal specimens received. Please provide maternal blood in addition to the fetal specimen. Additional charges apply for the maternal cell rule-out test.

  • All genetic testing performed on Direct CVS or Amniotic Fluid specimens will be confirmed on cell cultures prepared by Knight Diagnostic Laboratories. Cell cultures will be prepared from the specimen received. Additional charges apply for confirmatory testing.

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. Eggers, S., Sadedin, S., van den Bergen, J.A. et al. Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort. Genome Biol 17, 243 (2016).

  2. Lee PA, Houk CP, Ahmed SF, Hughes IA. Consensus Statement on Management of Intersex Disorders. Pediatrics. (2006).

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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