Presentation: Neonate with congenital hypothyroidism

An otherwise healthy-term neonate was diagnosed with congenital hypothyroidism following an abnormal newborn blood spot test. She is clinically well, and her thyroid function testing has normalised after starting therapy. Her mother and older sister have been on thyroid replacement therapy from infancy. There are no documented maternal anti-thyroid antibodies.

Genomic testing should be considered if:

• the patient has congenital hypothyroidism, thyroid hypoplasia or agenesis with or without syndromic features;
• the patient has suspected thyroid dyshormonogenesis; or
• the patient has raised serum thyroid stimulating hormone (TSH) level:
  • with enlarged thyroid gland; or
  • in the absence of thyroid autoantibodies.

• 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.
• 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.
  • R145 Congenital hypothyroidism: This is a multi-gene panel and includes whole exome sequencing or a medium panel to look for small variants and exon-level copy number variants.
• If R145 is negative or if you feel that there is another likely diagnosis for hypothyroidism, consider the following tests:
  • R28 Congenital malformation and dysmorphism syndromes – microarray only.
• For tests that do not include WGS, including R145 and R28:
  • 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 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

• Gov.uk: Congenital hypothyroidism: initial clinical referral guidelines
• NHS England: National Genomic Test Directory

Resources:

• Cherella CE and Wassner AJ. ‘Congenital hypothyroidism: insights into pathogenesis and treatment‘. International Journal of Pediatric Endocrinology 2017: volume 2017, article number 11. DOI: 10.1186/s13633-017-0051-0

For patients

• British Thyroid Foundation: Your guide to congenital hypothyroidism
• Great Ormond Street Hospital for Children NHS Foundation Trust: Congenital hypothyroidism