• Test code: 04411
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit

Invitae Disorders of Male Sex Development Panel

Test description

The Invitae Disorders of Male Sex Development Panel analyzes up to 15 genes 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.

Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant can inform recurrence-risk assessment and genetic counseling.

Order test

Primary panel (8 genes)


Add-on Kallman Syndrome Genes (4 genes)

In a 46,XY individual with ambiguous or underdeveloped genitalia (hypogonadotrophic hypogonadism) and an absence of the sense of smell, a diagnosis of Kallman syndrome may tested by including the ANOS, CHD7, FGFR1, and HESX1 genes for no additional charge. Please note, the HESX1 gene has preliminary evidence in association with Kallman syndrome. Some clinicians may wish to include a gene which does not currently have a definitive clinical association, but which may prove to be clinically significant in the future.


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 Syndrome Gene (1 gene)

In 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. Testing of the DHCR7 gene is available at no additional charge.


  • 46,XY disorder of sex development (DSD)
    • 46,XY disorder of sex development with adrenal insufficiency
    • 5-Alpha reductase deficiency
    • Meacham syndrome
  • 46,XY complete gonadal dysgenesis (CGD)
    • Swyer syndrome

46,XY DSD is characterized by ambiguous genitalia with penoscrotal hypospadias, incomplete closure of the labial-scrotal folds, and dysgenetic testes that produce little or no sperm. Female reproductive organs may be present in some individuals, who may achieve pregnancy with assisted reproductive technology. Affected individuals are generally identified prenatally or at birth.

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. Affected individuals often present with primary amenorrhea. With hormone replacement therapy, affected individuals undergo normal puberty and may achieve pregnancy with assisted reproductive technology.

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 10-15% 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. Alterations in the AR gene are thought to cause 65-95% of androgen insensitivity syndrome. The remaining genes have been reported so rarely that their individual contributions to the overall burden of these conditions are uncertain.

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

SRY-related disorders of sex development exhibit complete penetrance with variable expressivity. The penetrance for AR, NR5A1, and SRD5A2 is estimated at 50%–90%. The penetrance for NROB1-, MAP3K1-, DHH-, and WT1-related conditions is not yet well-established, but is expected to be high.

Prevalence of disorders of male sex development is estimated at 1 in 10,000 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. Pasterski, V, et al. Impact of the consensus statement and the new DSD classification system. Best Pract. Res. Clin. Endocrinol. Metab. 2010; 24(2):187-95. PMID: 20541147
  14. 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
ANOS1 NM_000216.2
AR* NM_000044.3
ATRX NM_000489.4
CHD7 NM_017780.3
DHCR7 NM_001360.2
DHH NM_021044.2
FGFR1 NM_023110.2
HESX1 NM_003865.2
MAP3K1 NM_005921.1
NR0B1 NM_000475.4
NR5A1 NM_004959.4
SOX9* NM_000346.3
SRD5A2 NM_000348.3
SRY NM_003140.2
WT1 NM_024426.4

AR: CAG repeat numbers are not determined.
SOX9: Deletion/duplication analysis covers the promoter region.