Presentation: Clinical suspicion of McCune-Albright syndrome

A five-year-old girl is referred to your clinic for assessment of precocious puberty. On further examination, you notice multiple café-au-lait macules and one larger hyperpigmented area, running from the upper left arm to the neck and chest and stopping at the midline, which has an irregular, jagged border.

Genomic testing should be considered if the patient presents with:

• multiple café-au-lait macules: These usually appear on one side of the body and have a jagged, irregular ‘coast of Maine’ border;
• polyostotic fibrous dysplasia: These usually appear on one side of the body, typically in weight-bearing bones (such as legs) and can cause pain, abnormal bone growth and fractures; and
• endocrine dysfunction: The most common feature of endocrine dysfunction is precocious puberty, especially in girls (often presenting as vaginal bleeding).

Radiological and endocrinological investigations may initially be indicated if the condition is suspected.

• 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 those working within NHS Wales, please consult the All Wales Medical Genomics Service website for information on how to arrange testing.
• 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. For suspicion of McCune-Albright syndrome:
  • R327 Mosaic skin disorders (deep sequencing): This investigates a dermatological anomalies likely to have a mosaic single-gene cause. An appropriate sample type of affected tissue should be considered.
    • This test does not include whole genome sequencing, and therefore:
      • you can use your local Genomic Laboratory Hub 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.
  • If testing blood, an EDTA sample (purple-topped tube) is required for DNA testing. However, given that McCune-Albright syndrome is a mosaic condition, genomic diagnosis is most reliable from affected tissue (for example, through skin biopsy of an affected area). You may wish to discuss this with your local clinical genetics and/or dermatology team.
• 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

• DermNet: McCune-Albright syndrome
• GeneReviews: Fibrous dysplasia/McCune-Albright syndrome
• Genomics England: NHS Genomic Medicine Service (GMS) Signed Off Panels Resource
• NHS England: National Genomic Test Directory

References:

• Javaid MK, Boyce A, Appelman-Dijkstra N and others. ‘Best practice management guidelines for fibrous dysplasia/McCune-Albright syndrome: A consensus statement from the FD/MAS international consortium’. Orphanet Journal of Rare Diseases 2019: volume 14, issue 1, page 139. DOI: 10.1186/s13023-019-1102-9
• Spencer T, Pan KS, Collins MT and others. ‘The clinical spectrum of McCune-Albright syndrome and its management’. Hormone Research in Paediatrics 2020: volume 92, issue 6, pages 347–356. DOI: 10.1159/000504802

For patients

• Contact UK: McCune-Albright syndrome
• Fibrous Dysplasia Support Society
• MedlinePlus: McCune-Albright syndrome