Invitae Disorders of Male Sex Development Panel


Test description

The Invitae Disorders of Male Sex Development Panel analyzes three genes that are associated with sexual development that is inconsistent with a 46,XY chromosome complement. These disorders include 46,XY disorder of sex development (46,XY DSD) and 46,XY complete gonadal dysgenesis (46,XY CGD). Genetic testing of these genes may confirm a diagnosis and help guide treatment and gender assignment decisions. Identification of a disease-causing variant can guide genetic counseling and inform recurrence-risk assessment.

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Primary panel (3 genes)


Add-on androgen insensitivity genes (2 genes)

In a 46,XY individual with ambiguous genitalia and absent müllerian structures, if the presence of recognizable testicular material in the abdomen or inguinal canal is suspected and a diagnosis of androgen insensitivity is in question, clinicians may wish to broaden analysis by including genes that are associated with androgen insensitivity (AR) and 5-alpha reductase deficiency (SRD5A2). These genes can be added at no additional charge.


AR: CAG repeat numbers are not determined.

Add-on alpha-thalassemia X-linked intellectual disability gene (1 gene)

In a 46,XY individual with ambiguous genitalia, intellectual disability, characteristic dysmorphic facies, and alpha thalassemia, testing for ATRX may be indicated and can be included at no additional charge.


Add-on campomelic dysplasia gene (1 gene)

In a 46,XY individual with ambiguous genitalia and congenital bowing of long bones, a suspected diagnosis of campomelic dysplasia can be evaluated by testing the SOX9 gene. This gene can be tested at no additional charge.


Add-on Smith-Lemli-Opitz gene (1 gene)

Testing of DHCR7 may be appropriate for a 46,XY individual with ambiguous genitalia and a syndromic phenotype that is consistent with Smith-Lemli-Opitz syndrome and corroborated by an abnormal biochemical profile showing elevated serum concentration of 7-dehydrocholesterol (7-DHC) reductase. This gene can be added at no additional charge.


  • 46,XY disorder of sex development
    • 46,XY disorder of sex development with adrenal insufficiency
  • 46,XY complete gonadal dysgenesis

46,XY DSD is characterized by ambiguous genitalia with penoscrotal hypospadias, incomplete closure of the labial-scrotal folds, dysgenetic testes that produce little or no sperm. Female reproductive organs may be present in some individuals and fully develop into a uterus and fallopian tubes. These individuals are clinically identified prenatally or at birth. Gender assignment depends on clinical assessment of the degree of feminization and appropriate corrective surgery. Those assigned a female gender due to sufficiently developed internal reproductive organs undergo surgery to feminize the external genitalia and can support a pregnancy through zygote donation. Those assigned a male gender have hypospadias and chordee corrected but are infertile.

46,XY complete gonadal dysgenesis (46,XY CGD) is characterized by normal female external genitalia and internal Müllerian structures and undeveloped streak gonads with absent sperm. These individuals grow up as female individuals and experience primary amenorrhea. With hormone replacement therapy, they undergo normal puberty and can sustain pregnancies with zygote donation. They do not have features of Turner syndrome, which results from monosomy for the X chromosome.

Alterations of SRY are a rare cause of 46,XY DSD but cause up to 15% of 46,XY CGD. Pathogenic changes in NR5A1 account for approximately 10% of 46,XY DSD but are not associated with 46,XY CGD to date. Duplications of NR0B1 are a rare cause of 46,XY DSD or 46,XY CGD.

46,XY DSD or CGD can be inherited in a Y-linked, X-linked, or autosomal dominant manner.

SRY-related DSD exhibit complete penetrance with variable expressivity. The penetrance for NR5A1 and SRD5A2 is near complete (50%–90%).

Prevalence is estimated at 1 in 5,000 to 20,000.

  1. Achermann, JC, et al. Phenotypic spectrum of mutations in DAX-1 and SF-1. Mol. Cell. Endocrinol. 2001; 185(1-2):17-25. PMID: 11738790
  2. Ahmed, SF, et al. Society for Endocrinology UK guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development (Revised 2015). Clin. Endocrinol. (Oxf). 2015. PMID: 26270788
  3. Bashamboo, A, McElreavey, K. Human sex-determination and disorders of sex-development (DSD). Semin. Cell Dev. Biol. 2015; 45:77-83. PMID: 26526145
  4. Douglas, G, et al. Guidelines for evaluating and managing children born with disorders of sexual development. Pediatr Ann. 2012; 41(4):e1-7. PMID: 22494213
  5. Hiort, O, et al. Management of disorders of sex development. Nat Rev Endocrinol. 2014; 10(9):520-9. PMID: 25022812
  6. Iyer, AK, McCabe, ER. Molecular mechanisms of DAX1 action. Mol. Genet. Metab. 2004; 83(1-2):60-73. PMID: 15464421
  7. King, TF, Conway, GS. Swyer syndrome. Curr Opin Endocrinol Diabetes Obes. 2014; 21(6):504-10. PMID: 25314337
  8. Köhler, B, et al. Five novel mutations in steroidogenic factor 1 (SF1, NR5A1) in 46,XY patients with severe underandrogenization but without adrenal insufficiency. Hum. Mutat. 2008; 29(1):59-64. PMID: 17694559
  9. Lin, L, et al. Heterozygous missense mutations in steroidogenic factor 1 (SF1/Ad4BP, NR5A1) are associated with 46,XY disorders of sex development with normal adrenal function. J. Clin. Endocrinol. Metab. 2007; 92(3):991-9. PMID: 17200175
  10. Ostrer, H. 46,XY Disorder of Sex Development and 46,XY Complete Gonadal Dysgenesis. 2008 May 21. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301714
  11. Ostrer, H. Disorders of sex development (DSDs): an update. J. Clin. Endocrinol. Metab. 2014; 99(5):1503-9. PMID: 24758178
  12. Paris, F, et al. Disorders of sex development: neonatal diagnosis and management. Endocr Dev. 2012; 22:56-71. PMID: 22846521
  13. White, S, et al. Copy number variation in patients with disorders of sex development due to 46,XY gonadal dysgenesis. PLoS ONE. 2011; 6(3):e17793. PMID: 21408189

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
AR* NM_000044.3
ATRX NM_000489.4
DHCR7 NM_001360.2
NR0B1 NM_000475.4
NR5A1 NM_004959.4
SOX9 NM_000346.3
SRD5A2 NM_000348.3
SRY NM_003140.2

AR: CAG repeat numbers are not determined.