Disorders of sex development


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Inclusion Criteria 

46,XX disorder of sex development

  • Normal 46,XX karyotype following microarray testing, AND
  • Absence of SRY, AND
  • At least one of (a) genital ambiguity, (b) absence or anomaly of the Mullerian structures, or (c) gonadal dysgenesis

46,XY disorder of sex development

  • Normal 46,XY karyotype following microarray testing, AND
  • Presence of SRY, AND
  • At least one of (a) ambiguity of the external genitalia, (b) presence of Mullerian structures, or (c) gonadal dysgenesis

Exclusion Criteria

46,XX disorder of sex development

  • Antenatal history suggestive of non-genetic cause, e.g. maternal androgen exposure
  • Biochemical or genetic evidence of 21-hydroxylase deficiency, 11-hydroxylase deficiency, 3 beta hydroxysteroid dehydrogenase deficiency type 2, cytochrome P450 reductase (POR) related disorders and 17 alpha hydroxylase deficiency.
    46,XY disorder of sex development
  • Isolated hypospadias
  • Biochemical or genetic evidence of 5 alpha reductase deficiency, 3 beta hydroxysteroid dehydrogenase deficiency type 2, cytochrome P450 reductase (POR) related disorders, aromatase deficiency and androgen insensitivity syndrome.

Prior genetic testing guidance

  • Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition.
  • Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture toolto allow comparison of WGS with current standard testing.

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Prior genetic testing genes

Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice:

46,XX disorder of sex development

  • In situ study to exclude presence of SRY
  • Exclusion of CNV associated with 46 XX DSD
  • CYP21A2 and CYP11B1 if indicated by steroid biochemistry – steroid biochemistry to assess whether these disorders needed genetic testing would be a requirement before inclusion.

46,XY disorder of sex development

  • In situ study to prove presence of SRY
  • Exclusion of CNV associated with 46 XY DSD
  • Obligatory endocrinological assessment and steroid biochemistry (including testosterone, DHT) and where indicated from biochemical investigations analysis of HSD17B3, SRD5A2 and Androgen receptor)

Closing statement

These requirements will be kept under continual review during the main programme and may be subject to change.

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