Presentation: Child with yellow or brown teeth that are ‘crumbly’

An 11-year-old patient attends with sensitivity of his teeth and reports getting bullied at school due to their appearance. There is no history of excess fluoride consumption and his dad thinks that some other family members are also affected. On examination, the teeth are small and yellow and all teeth from both the primary and secondary dentitions are affected. His front teeth don’t meet together when biting.

Amelogenesis imperfecta is a rare disease that affects the formation of dental enamel. Enamel anomalies affecting unerupted permanent teeth can be detected on dental radiographs, meaning that information about both dentitions is available well before eruption of the first permanent tooth.

If amelogenesis imperfecta is suspected in general dental practice, a referral to a specialist-led service should be considered (either paediatric dentistry or restorative dentistry).

Genomic testing should be considered in individuals in whom a clinical diagnosis of amelogenesis imperfecta is suspected. This requires discussion with the family, and shared decision-making principles should apply. The National Genomic Test Directory eligibility criteria for genomic testing are:

• significant developmental anomalies in enamel quality and/or quantity affecting all or nearly all teeth of both dentitions (primary and secondary); and
• environmental factors excluded.

Genomic testing can be requested by clinical geneticists or dentists with an expertise in developmental dental conditions.

If your patient does not meet these criteria, but you have a strong clinical suspicion of an inherited cause, discuss with your local Genomic Laboratory Hub (GLH).

• 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 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.
• For investigation of possible amelogenesis imperfecta, the appropriate panel to choose is:
  • R340 Amelogenesis imperfecta. This is a gene panel test covering a small number of genes, pathogenic variants in which are known to cause amelogenesis imperfecta.
• The majority of genomic tests in adults are currently undertaken on a singleton basis, though samples may be needed from additional family members in order to interpret results.
• When testing in children, parental samples may be helpful 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.
• None of the tests outlined above use whole genome sequencing, so you should use your local GLH test order form and consent (record of discussion) form.
• 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

• Medline Plus: Amelogenesis imperfecta
• National Organization for Rare Disorders: Amelogenesis imperfecta
• OMIM: Phenotypic series PS104500: Amelogenesis imperfecta

References:

• Bloch-Zupan A, Rey T, Jimenez-Armijo A and others. ‘Amelogenesis imperfecta: Next-generation sequencing sheds light on Witkop’s classification‘. Frontiers in Physiology 2023: volume 14. DOI: 10.3389/fphys.2023.1130175
• Smith CEL, Poulter JA, Antanaviciute A and others. ‘Amelogenesis imperfecta: Genes, proteins, and pathways‘. Frontiers in Physiology 2017: volume 8. DOI: 10.3389/fphys.2017.00435