Presentation: Patient with sparse hair and peg-shaped teeth

A family is concerned that their son has a genetic condition. He never grew much hair on his scalp, and his baby teeth are atypical, with some missing and some cone-shaped. He had several seizures as an infant in the context of febrile illness and he has never produced much sweat. He has slightly dry skin and occasional flares of mild eczema. His mother has noticed that some of her own teeth are also cone-shaped.

• Genomic testing should be considered for individuals with a clinical diagnosis of ectodermal dysplasia (ED) based on the presence of one or more of the following:
  • anomalies of hair (hypotrichosis, sparse hair, sparse or missing eyebrows);
  • anomalies of teeth (hypodontia, conical incisors); and/or
  • anomalies of skin (hypohidrosis, episodes of hyperthermia).
• The genetic classification of EDs can be divided into:
  • EDA/NF KappaB pathway;
  • WNT pathway;
  • TP63 pathway;
  • structure group (proteins important for the structure or function of the cell); and
  • other/unknown.
• The most common form of ED is X-linked recessive, which means that it affects males more commonly.

• 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 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.
• Decide which of the clinical indication codes best suits the needs of your patient and/or family. If ED is strongly suspected, the following indication should be considered:
  • R163 Ectodermal dysplasia: This currently tests for genes known to cause ED, and includes gene panel sequencing and multiplex ligation-dependent probe amplification (MLPA).
• If incontinentia pigmenti is suspected clinically, the following panel should be considered:
  • R239 Incontinentia pigmenti: This involves IKBKG single gene sequencing.
• None of the tests outlined above use whole genome sequencing, so you should use your local Genomic Laboratory Hub test order form and consent (record of discussion) form.
• 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.
• 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

• National Organization for Rare Disorders: Ectodermal dysplasias

For patients

• ED Society
• National Foundation for Ectodermal Dysplasias