Presentation: Fetus with ambiguous genitalia

A couple present for their anomaly scan at 21 weeks of pregnancy. The sonographer notices some concerning features in the perineal region when assessing the femur length. The couple are referred to their local fetal medicine unit, where ambiguous genitalia is identified.

• When ambiguous or discordant genitalia is identified on antenatal imaging.
• When there is a confirmed history of a previous pregnancy affected by congenital adrenal hyperplasia (CAH).
  • See: Presentation: Pregnancy at risk of congenital adrenal hyperplasia
• When there is a family history of CAH and/or known carrier status in either parent.

• Consult the National Genomic Test Directory. From this directory you can access the rare and inherited disease eligibility criteria for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet of all available tests.
  • For those working within NHS Wales, please consult the All Wales Medical Genomics Service website for information on how to arrange testing.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• Collect a detailed family and personal history from both parents.
• Refer the family to clinical genetics for review by a clinical geneticist or genetic counsellor and/or to your local fetal medicine unit, dependant on local protocol.
• Testing options may include:
  • R251 Sex determination Non-invasive prenatal diagnosis:
    • Females affected by CAH are at risk of developing virilisation of the genitalia with clitoromegaly. If the fetus is female, consider invasive testing for diagnostic purposes.
  • Invasive testing: may be offered as a primary investigation for diagnostic purposes, or where this is the patient’s preference:
    • R180 Congenital adrenal hyperplasia diagnostic test: This will target both:
      • R180.1 CYP21A2 Single gene sequencing; and
      • R180.2 CYP21A2 Multiple ligation-dependent probe amplification (MLPA) or equivalent.
• For tests that are undertaken using whole genome sequencing (WGS), you will need to:
  • complete an NHS GMS test order form with details of the proband and parents. Include details of the phenotype (refer to human phenotype ontology (HPO) terms or the clinical summary) and the appropriate panel name(s) with associated R number (see How to complete a test order form for WGS for support).
  • complete an NHS GMS ROD form for each person being tested. Note that, if you are undertaking trio testing of an affected child and their parents, you will need three of these forms. (see How to complete a record of discussion form for support).
  • parental samples should be submitted alongside the child’s sample. This is called trio testing. If this is not possible, such as when testing a child in care or a parent is unavailable for testing, the child may be tested as a singleton.
• For tests that do not include WGS, you will need to:
  • complete a test order form and consent (record of discussion) form, available from your local Genomic Laboratory Hub (GLH).
  • include details of the phenotype in the test order form (refer to HPO terms or the clinical summary) as well as the appropriate panel name(s) with associated R number.
  • parental samples may be needed for interpretation of the proband’s result. Parental samples can be taken alongside that of the proband, and their DNA stored, or can be requested at a later date if needed.
• For invasive tests, an amniocentesis or chorionic villus sample or fetal blood sample is required using an EDTA tube (purple-topped).
  • Postnatal testing at birth may include genomic testing, electrolyte and urine steroid profiles. The baby would need monitoring for salt-losing crisis until results are available.
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• Great Ormond Street Hospital for Children NHS Foundation Trust: Congenital adrenal hyperplasia (CAH) information
• National Organization for Rare Disorders: Congenital adrenal hyperplasia information
• NHS England: National Genomic Test Directory and eligibility criteria

For patients

• Great Ormond Street Hospital for Children NHS Foundation Trust: Congenital adrenal hyperplasia (CAH) information (PDF, three pages)
• Great Ormond Street Hospital for Children NHS Foundation Trust: Non-invasive prenatal diagnosis (NIPD) information