Presentation: Neonate with failure to pass meconium

A full-term neonate, born via normal vaginal delivery, is now 48 hours old and has yet to pass their first stool. The mother had an uneventful pregnancy with normal antenatal scans. The newborn’s abdominal X-ray shows multiple dilated loops of bowel.

• Genomic testing should be considered if:
  • Hirschsprung disease is diagnosed clinically; or
  • there is a structural bowel malformation and/or other congenital anomalies suggestive of a syndromic diagnosis.
• Cystic fibrosis should be investigated if meconium ileus is suspected or diagnosed.

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria, which provides information about individual tests and their associated eligibility criteria. You can also access a spreadsheet containing details 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.
• Decide which of the panels best suits the needs of your patient or family. For failure to pass meconium, there are a number of available panels.
• • R177 Hirschsprung disease. Consider this test if there is a clinical diagnosis of Hirschsprung disease.
• • R27 Paediatric disorders. Consider this test if there is structural bowel malformation and/or other congenital malformation suggestive of a syndromic diagnosis.
• • R184 Cystic fibrosis diagnostic test. This is the full cystic fibrosis variant test (not just the common CFTR pathogenic variant test), and should be considered if meconium ileus is diagnosed and sweat test results are abnormal or there is an additional urgent prenatal situation for the parents or for a close relative and the urgent sweat test is not available.
• For tests that are undertaken using whole genome sequencing (WGS), including R27, you will need to:
• • complete an NHS GMS test order form with details of the affected child (proband) and their parents, including details of the phenotype (using human phenotype ontology (HPO) terms) and the appropriate panel name(s) with associated R number (see How to complete a test order form for WGS for support in completing WGS-specific forms);
• • complete an NHS GMS record of discussion (RoD) form for each person being tested – for example, if you are undertaking trio testing of an affected child and their parents, you will need three RoD forms (see How to complete a record of discussion form for support); and
• • submit parental samples alongside the child’s sample (this is trio testing) to aid interpretation, especially for the larger WGS panels (where this is not possible, for example because the child is in care or the parents are unavailable for testing, the child may be submitted as a singleton).
• For tests that do not include WGS, including R177 and R184:
• • you should use your local Genomic Laboratory Hub test order and consent (RoD) forms; and
• • parental samples may be needed for interpretation of the child’s result. Parental samples can be taken alongside that of the child, and their DNA stored, or can be requested at a later date if needed.
• The majority of tests are DNA based, and an EDTA sample (purple-topped tube) is required. Exceptions include karyotype testing and DNA repair defect testing (for chromosome breakage), which require lithium heparin (green-topped tube).
• R27 is a large WGS ‘super panel’ (a panel comprised of several different constituent panels forming one large panel), and requesting it currently requires authorisation from clinical genetics services.
• 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

• Genomics England: NHS Genomic Medicine Service (GMS) Signed Off Panels Resource
• NICE: Cystic fibrosis
• NHS England: National Genomic Test Directory

References:

• Mataya L and Lysouvakon P. ‘Delayed passage of meconium, abdominal distention, and emesis in a 2-day old girl’. Pediatrics in Review 2019: volume 40, issue 6, pages 310–312. DOI: 10.1542/pir.2017-0069

For patients

• NHS Health A to Z: Cystic fibrosis
• NHS Health A to Z: Hirschsprung’s disease
• NHS England: Whole genome sequencing patient information leaflets