Presentation: Pregnancy at risk of congenital adrenal hyperplasia

A couple in their third pregnancy present at the booking appointment. They inform the midwife that their second pregnancy was complicated by fetal anomalies and that postnatal genomic testing confirmed a diagnosis of congenital adrenal hyperplasia (CAH). Both parents were subsequently diagnosed as carriers of the genetic variant causing this disease.

• When there is a confirmed history of a previous pregnancy affected by CAH.
• When there is a family history of CAH and/or either parent is known to be a carrier.
• When clinical features in the fetus are suggestive of CAH.

• Collect a detailed family and personal history from the couple.
• Refer to clinical genetics for review by a clinical geneticist or genetic counsellor.
• The clinical genetics team will review the NHS England National Genomic Test Directory eligibility criteria, which identifies the tests for which patients are eligible. The directory itself provides a list 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.
• Testing options may include:
  • R251 Non-invasive prenatal diagnosis (NIPD) for fetal sexing: 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.
  • R250 NIPD for CAH: This can be offered from 8 to 10 weeks’ gestation for pregnancies at risk of CAH where both parents have been confirmed as carriers.
    • Control samples are required, which may include:
      • maternal and paternal DNA samples demonstrating prior carrier status; and
      • DNA samples from a previous affected pregnancy.
    • Invasive testing may be offered as a primary investigation owing to patient preference or availability of NIPD.
  • For NIPD, a blood sample in an EDTA tube is required. For many of the tests, parental samples are also needed or are helpful. Please refer to your local Genomic Laboratory Hub (GLH) for details of test request forms and where to send samples.
  • For invasive tests, an amniocentesis or chorionic villus sample or fetal blood sample (in an EDTA tube) is required. For many of the tests (particularly whole genome and exome sequencing), parental samples are also needed or are helpful. Please refer to your local GLH for details of test request forms and where to send samples.
  • A record of discussion form, or another appropriate local consent form, is required for testing.
• 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 2016: Non-invasive prenatal diagnosis
• National Organisation for Rare Disorders: Congenital adrenal hyperplasia
• NHS England: National Genomic Test Directory

For patients

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