Presentation: Clinical suspicion of cystic fibrosis

A one-year-old boy is referred to the paediatric clinic by his GP because of poor growth. He is tracking below the 0.4th centile with no easily identifiable cause. He has had several respiratory tract infections, which leads you to suspect that he may have cystic fibrosis. The family moved to the UK recently and he did not have newborn screening.

Consider genomic testing for cystic fibrosis in a child with any of the following clinical features plus an abnormal sweat test (rarely, sweat test results are not required – for instance when testing is urgent or a sweat test is not practically possible):

• failure to thrive;
• recurrent chest infections;
• fat malabsorption (bloating, diarrhoea, difficult-to-flush stool); and/or
• neonatal history of meconium ileus.

Sweat testing must be performed in a recognised, experienced test centre or laboratory; a ‘not normal’ sweat test result is defined as sweat chloride at or more than 30mmol/L with sufficient sweat obtained.

In the prenatal setting, cystic fibrosis may be suspected in the presence of echogenic bowel (as bright as bone) on the second trimester scan, or dilated fetal bowel on the second or third trimester scan with echogenic bowel. In this situation, urgent parental carrier testing should be offered initially.

• Consult the National Genomic Test Directory. From here 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 Genomic testing in the devolved nations.
• For information about the genes that 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 clinical suspicion of cystic fibrosis in a child who meets the eligibility criteria given above, the appropriate test is:
    • R184 Cystic fibrosis diagnostic test: This requests compound testing, which includes targeted variant testing of CFTR, followed by single gene sequencing and multiplex ligation-dependent probe amplification (MLPA) of CFTR.
• For tests that do not include whole genome sequencing (WGS), including R184:
  • you can use your local Genomic Laboratory Hub (GLH) test order and consent (record of discussion) 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.
• Most tests are DNA based, and an EDTA sample (typically a purple-topped tube) is required. There are a few tests for which a different type of tube is used; see Samples for genomic testing in rare disease.
• If your patient is diagnosed with cystic fibrosis, the result may have significant implications for family members. Consider referral to clinical genetics services for counselling and carrier testing.
• If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.
• 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
• NHS England: National Genomic Test Directory
• OMIM: 219700 Cystic fibrosis; CF
• Patient.info: Cystic fibrosis (professional article)

References:

• VanDevanter DR, Kahle JS, O’Sullivan AK and others. ‘Cystic fibrosis in young children: A review of disease manifestation, progression, and response to early treatment’. Journal of Cystic Fibrosis 2016: volume 15, issue 2, pages 147–157. DOI: 10.1016/j.jcf.2015.09.008

For patients

• Asthma and Lung UK: Cystic fibrosis
• Cystic Fibrosis Foundation
• Cystic Fibrosis Trust