Presentation: Child with generalised arterial calcification 

A two-month-old boy is referred to the paediatric cardiology clinic due to respiratory distress, congestive heart failure and systemic hypertension. A chest x-ray shows an enlarged cardiac silhouette, and an electrocardiogram (ECG) reveals a left ventricular strain pattern. An echocardiogram shows a calcification of the coronary arteries as well as in the descending aorta and pulmonary arteries.

• Consider genomic testing if a patient is:
  • a neonate with an antenatal diagnosis of arterial calcifications, atypical cardiac contractility, non-immune hydrops and/or hyperechoic kidneys; or
  • an infant presenting with widespread arterial calcification and/or narrowing of large and medium-sized vessels, resulting in cardiovascular findings such as heart failure, respiratory distress, oedema, cyanosis and/or hypertension.
• Testing should be carried out in parallel with expert phenotypic assessment – for example in an inherited cardiac conditions (ICC) clinic or specialist paediatric cardiology service – and with support from clinical genetics. Note that testing may occasionally be appropriate outside these criteria following discussion in an ICC multidisciplinary team meeting.

• 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 containing details 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.
• If the relevant eligibility criteria are met, discuss the case with or refer it to your local ICC clinical service for genomic testing and family screening. You will need to provide details confirming that the patient fulfils the criteria.
• If the patient fulfils diagnostic criteria as detailed in published guidelines that differ from the eligibility criteria in the test directory, it is appropriate to refer the case to an ICC clinic for further assessment.
• The relevant testing panel for generalised arterial calcification of infancy is:
  • R384.1 Generalised arterial calcification of infancy: This indication includes small gene panel sequencing to identify any variants in the ABCC6 and ENPP1 genes.
• The majority of genomic tests for ICCs are currently undertaken on a singleton basis, although samples may be needed from additional family members in order to interpret results.
• For tests that do not include whole genome sequencing (WGS), you will need to:
  • complete a test order form and consent (record of discussion) form, available from your local Genomic Laboratory Hub; and
  • include on the test order form details of the phenotype (using human phenotype ontology (HPO) terms or the clinical summary) and the appropriate panel name(s) with associated R number.
• The majority of tests (including DNA storage) 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

• GeneReviews: Generalized arterial calcification of infancy
• NHS England: National Genomic Test Directory
• OMIM: #208000 Generalized arterial calcification of infancy-1 (GACI1)
• OMIM: #614473 Generalized arterial calcification of infancy-2 (GACI2)
• Orphanet: Generalized arterial calcification of infancy
• National Organization for Rare Disorders: Generalised arterial calcification of infancy

References:

• Ferreira CR, Hackbarth ME, Ziegler SG and others. ‘Prospective phenotyping of long-term survivors of generalized arterial calcification of infancy (GACI)’. Genetics in Medicine 2021: volume 23, issue 2, pages 396–407. DOI: 10.1038/s41436-020-00983-0

For patients

• Contact: Generalised arterial calcification of infancy
• GACI Global: What is generalised arterial calcification of infancy?