Presentation: Pregnancy with suspicion of a skeletal dysplasia

A patient has a growth scan at 32 weeks of pregnancy after an episode of reduced fetal movements. The scan identified a short femur length and a fetal medicine referral was made. When measured, all the long bones were 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.
• When there is a family history of a skeletal dysplasia or other skeletal abnormality.
• Look at the parents carefully for short stature or disproportion (important when analysing the trio exome sequencing).

• 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 information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• Refer to local guidance regarding a fetal medicine and/or clinical genetics 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 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: This indication includes fetal exome sequencing. Referral to clinical genetics and/or multidisciplinary discussion is required.
  • R309 NIPD for FGFR3-related skeletal dysplasias – mutation testing: This can be requested in isolation if scan findings are suggestive of achondroplasia or thanatophoric dysplasia. This can be via non-invasive prenatal diagnosis (NIPD). A blood sample in a Streck tube is required.
• For whole genome sequencing (WGS)-based tests, 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 and 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 record of discussion (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).
• For tests that do not include WGS, you will need to:
  • complete a test order form and consent (ROD) form, available from your local Genomic Laboratory Hub (GLH); and
  • include details of the phenotype (refer to HPO terms or the clinical summary) as well as the appropriate panel name(s) with associated R number.
• For invasive tests, an amniocentesis or chorionic villus sample or fetal blood sample in an EDTA (purple topped) tube is required. For many of the tests (particularly whole genome and exome sequencing), parental samples are also needed or are helpful.
• 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
• GeneReviews: Skeletal Dysplasias
• NHS England: National Genomic Test Directory
• UpToDate: Skeletal dysplasias: Approach to evaluation

For patients

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