Presentation: Pregnancy with suspicion of a skeletal dysplasia

A primigravid (first-time pregnant) woman is referred to fetal medicine because she has just had a growth scan at 32 weeks’ gestation after an episode of reduced fetal movements. When measured, all the long bones are below the first centile. Her fetal anomaly scan at 20 weeks was unremarkable.

• When the long bones are over two standard deviations below the mean in the second or third trimester.
• When there are signs of bowing or fractures in the long bones.
• When there are short long bones associated with:
  • an unusual head shape;
  • a small chest size;
  • hand or foot anomalies;
  • widened proximal femoral metaphyseal angle (achondroplasia); and
  • atypical bone mineralisation.
• When abdominal circumference is normal and there is no evidence of placental insufficiency.
• Look at the parents carefully for short stature or disproportion (important when analysing the trio exome sequencing).

• Refer to local guidance regarding a fetal medicine referral.
• A genetic referral is not always indicated. The fetal medicine review will determine whether genomic testing is appropriate, and referral to clinical genetics can be considered in certain circumstances.
• The relevant team will refer to the NHS England National Genomic Test Directory eligibility criteria to determine which tests are available to your patient. 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.
• The fetal medicine team will decide which of the panels best suits the needs of your patients and/or will discuss the case with a multidisciplinary team, depending on the specific clinical scenario and the patients’ wishes. For skeletal dysplasias, there are a number of available panels. These include:
  • R22 Fetus with a likely chromosomal abnormality. This will process both:
    • R22.1 Genome-wide common aneuploidy testing; and
    • R22.2 Chromosomal microarray.
  • Skeletal dysplasias are likely to be monogenic, therefore fetal exome sequencing may be considered and performed in parallel with R22:
    • R21 Fetal anomalies with a likely genetic cause: fetal exome sequencing.
  • Referral to clinical genetics and/or multidisciplinary discussion is required.
  • A record of discussion form is required (for each parent).
    • R104 (skeletal dysplasia panel): an R104 can be considered if the long bones are over 3.5 standard deviations below the mean; however, R21 testing would cover this panel.
    • FGFR3 testing in isolation if scan findings are suggestive of achondroplasia during non-invasive prenatal diagnosis (NIPD) or fetal sample (NIPD is generally preferred during the third trimester to avoid premature delivery).
• 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 Genomic Laboratory Hub (GLH) for details of test request forms and where to send samples.
• If achondroplasia or thanatophoric dysplasia are suspected, NIPD may be considered. A blood sample in a Streck tube is required. Please refer to your local GLH for details of test request forms and where to send samples.
• 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

• Fetal Medicine Foundation: Skeletal dysplasia
• NHS England: National Genomic Test Directory
• UpToDate: Skeletal dysplasias: Approach to evaluation

For patients

• Gov.uk: Severe skeletal dysplasia: Information for parents