Presentation: Fetus with an isolated short femur

A primigravid (first-time pregnant) woman is referred to fetal medicine because she has just had her fetal anomaly ultrasound at 20 weeks’ gestation and, although the head circumference and the abdominal circumference plot onto the 50th centile, the femur length is on the first centile.

• When the femur length in the second or third trimester is less than the first centile for gestational age.
• When the femur length is disproportionately small compared with the head circumference and abdominal circumference.
• When there are other anomalies noted on ultrasound other than short femur length.
• When there are other bony anomalies seen on a scan (unusual head shape, small chest size, signs of bowing or fractures in the long bones – see Presentation: Pregnancy with suspicion of a skeletal dysplasia).
• When there is no evidence of placental insufficiency.
• When there is a higher-chance first- or second trimester screening result, or when the parents have previously declined screening but now wish to receive it.
• When there is a family history of skeletal abnormalities or significant short stature (>3 standard deviations).

• 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.
• Take a detailed history, which should include:
  • Family history of short stature.
  • Family history of skeletal problems.
  • Look carefully at both parents for height and disproportion.
• Refer to local guidance regarding fetal medicine referral. Further review in a fetal medicine unit is usually warranted.
• A fetal medicine review will determine whether genomic testing is appropriate and referral to clinical genetics will be considered.
• Depending on the clinical scenario, a range of different genomic tests may be considered:
  • R22 Fetus with a likely chromosomal abnormality. This will process both:
    • R22.1 Genome-wide common aneuploidy testing; and
    • R22.2 Chromosomal microarray.
  • Where there are multiple or complex anomalies and/or above testing is non-diagnostic, fetal exome sequencing may be considered:
    • R21 Fetal anomalies with a likely genetic cause: fetal exome sequencing.
      • Referral to clinical genetics and/or multidisciplinary discussion is required.
• For many of the tests (particularly whole genome and exome sequencing), parental samples are also needed or are helpful.
• 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.
• All of the above tests are DNA based and an EDTA sample (purple-topped tube) is required.
• 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

• NHS England: National Genomic Test Directory

References:

• Benacerraf BR, Gelman R and Frigoletto Jr FD. ‘Sonographic identification of second-trimester fetuses with Down’s syndrome.’ The New England Journal of Medicine 1987: volume 317, issue 22, pages 1,371–1,376. DOI: 10.1056/NEJM198711263172203
• Nyberg DA, Resta RG, Hickok DE and others. ‘Femur length shortening in the detection of Down syndrome: Is prenatal screening feasible?‘ The American Journal of Obstetrics and Gynecology 1990: volume 162, issue 5, pages 1,247–1,252. DOI: 1016/0002-9378(90)90028-6
• Nyberg DA, Souter VL, El-Bastawissi A and others. ‘Isolated sonographic markers for detection of fetal Down syndrome in the second trimester of pregnancy.’ Journal of Ultrasound in Medicine 2001: volume 20, issue 10, pages 1,053–1,063. DOI: 10.7863/jum.2001.20.10.1053