Presentation: Adult with multiple early-onset cutaneous basal cell carcinomas

A family is concerned that their 21-year-old daughter has developed multiple lesions on sun-exposed areas of her face and shoulders. She previously developed a painful cyst in her jaw, which had to be drained two years ago. Recently, she has also noticed small pits forming on the palms of her hands and the soles of her feet after being in the bath.

• The most common cause of multiple basal cell carcinomas (BCCs) is nevoid basal cell carcinoma syndrome. This condition is most often caused by pathogenic variants in PTCH1 or SUFU.
• The genomic test R214 Nevoid basal cell carcinoma syndrome or Gorlin syndrome is indicated in an affected individual where the clinical history meets:
  • ≥ 1 major criteria from the list below; or
  • ≥ 2 minor criteria from the list below.

Major criteria

• Lamellar (sheet-like) calcification of the falx or clear evidence of calcification in an individual younger than 20 years of age.
• Jaw keratocyst: odontogenic keratocyst histologically.
• Palmar/plantar pits (two or more).
• Sonic hedgehog (SHH) medulloblastoma, confirmed on tumour testing.
• Multiple BCCs (>5 under 50 years of age).

Minor criteria

• Childhood medulloblastoma where SHH pathway in the tumour has not been investigated (this is also called a primitive neuroectodermal tumour).
• Lympho-mesenteric or pleural cysts.
• Macrocephaly (occipital frontal circumference (OFC) >97th centile).
• Cleft lip and/or palate.
• Vertebral and/or rib anomalies observed on chest x-ray and/or spinal x-ray; bifid, splayed or extra ribs; bifid vertebrae.
• Preaxial or postaxial polydactyly.
• Ovarian and/or cardiac fibromas.
• Ocular anomalies (cataract, developmental defects and/or pigmentary changes of the retinal epithelium).

• 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.
• For information about the genes that are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• Decide which of the tests best suits the needs of your patient and/or family.
• If you suspect naevoid basal cell carcinoma syndrome, the correct test to order is:
  • R214 Nevoid basal cell carcinoma syndrome or Gorlin syndrome: This includes gene panel sequencing and multiplex ligation-dependent probe amplification (MLPA) for PTCH1 and SUFU.
• 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. Exceptions include karyotype testing and DNA repair defect testing (for chromosome breakage), which require lithium heparin (typically a green-topped tube). For more information, 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

• StatPearls: Gorlin syndrome

For patients

• British Association of Dermatologists: Basal cell carcinoma
• Gorlin Syndrome Alliance
• Gorlin Syndrome Group