Basal cell naevus syndrome is a raregeneticcancersyndrome characterised by multiple early onsetbasal cellcarcinomas,odontogenickeratocysts and othertumours, and otherabnormalities.
Basal cell naevus syndrome (BCNS) is probably best known as Gorlin syndrome, and is also callednaevoidbasal cellcarcinomasyndrome, amongst many other names.
Basal cell naevus syndrome
Who gets basal cell naevus syndrome?
Basal cell naevus syndrome is anautosomaldominant genetic disorder affecting males and females equally. Although seen in all races, race does influenceincidenceandpenetrancewith Gorlin syndrome rarely diagnosed in Black Americans and Asians. Theprevalenceis difficult to determine as although Gorlin syndrome has high penetrance, expressivity is variable and sporadicmutationsare found in 50%. Estimates of prevalence range from 1/57,000 to 1/256,000.
What causes basal cell naevus syndrome?
Basal cell naevus syndrome is the result of genetic mutations affecting the sonic hedgehog signalling pathway, a pathway crucial for proper celldifferentiation.Genesimplicated in Gorlin syndrome includePTCH1,PTCH2, andSUFU.
What are the clinical features of basal cell naevus syndrome?
- Multiple early onset cutaneous basal cell carcinomas (BCC)
- Palmoplantarpits in up to 87%, often present in childhood
- Webbing of fingers and toes
- Milia andepidermoidcysts
Image Credit forpalmarpits in skin of colour: Poladian K, Difato TC, Anderson KL, Taylor SL. Gorlin syndrome in a patient with skin type VI. Dermatol Online J. 2019;25(11):13030/qt64c4p1sq.
- Characteristicfacies— increased head circumference, hypertelorism, broad nasal root, fronto-parietal bossing, and enlargedmandible
- Skeletal abnormalities include bifid, splayed or fused ribs; kyphoscoliosis, wedge-shaped vertebrae;polydactyly,syndactyly; funnel chest (pectus excavatum) and pigeon chest (pectus carinatum)
- Odontogenic keratocysts
- Usually located in the mandible
- Seen in up to 80%
- Present in the second and third decade
- Oftenasymptomaticbut may causepathologicalfracture and abnormal dentition
- Medulloblastoma — develops in childhood, found in 5%; only 3% of patients with medulloblastoma have BCNS
- 20x more common in those with aSUFUmutation
- Ovarianfibromas— in 20% of females;bilateral; calcified
- Corneal opacity,cataract,glaucoma,strabismus, retinalpigmentation,congenitalblindness
- Calcificationof falx cerebri in 90% by age 20 years
- Gynaecomastiaandhypogonadismin males
- Cleftlip andpalate, high arched palate
- Lymphaticcysts of the mesentery
- Intellectual impairment in up to 5%
How do clinical features vary in differing types of skin?
Basal cell carcinomas are seen in 80-90% of pale-skinned patients with Gorlin syndrome. Black patients may have < 2 skin cancers; 20% of dark-skinned Africans with Gorlin syndrome have none.
What are the complications of basal cell naevus syndrome?
- AggressiveinvasiveBCC on the eyelid or nose associated with local tissue destruction and highrecurrencerate after treatment
- Metastaticcancer (rare)
- Psychosocialeffectsresulting from the many skin tumours and their treatment
How is basal cell naevus syndrome diagnosed?
Basal cell naevus syndrome can be diagnosed on clinical criteria alone but may require investigations to confirm it in some cases, particularly in children. The BCChistologyis the same as for sporadic BCC [seeBasal cell carcinomapathology].
The diagnosis is made if there are two major criteria, or one major and two minor criteria.
- Five or more basal cell carcinomas in a lifetime, or BCC before age 20 years, or excessive numbers out of proportion to prior sun exposure or skin type
- Histologicallyprovenodontogenic keratocyst
- Palmar and/orplantarpits (3 or more)
- Lamellar calcification or obvious calcification of the falx cerebri before the age of 20 years
- Bifid, fused, or splayed ribs
- First degree relativewith basal cell naevus syndrome
- Macrocephalywith occipitofrontal circumference > 97th percentile
- Congenitalmalformations, including lymphomesenteric orpleuralcysts,cleft lipor palate
- Skeletal abnormalities
- Cardiac or ovarian fibroma
What is thedifferential diagnosisfor basal cell naevus syndrome?
- Chronicsun exposure
- Xeroderma pigmentosum
- Othergenodermatoseswith multiple BCC —includingBazex-Dupré-Christol syndrome, Rombo syndrome
What is the treatment for basal cell naevus syndrome?
General measures and screening
- Genetic counselling
- Sun protection
- BrainMRIscreening every 6 months for medulloblastoma to age 3 years, then annual for age 3–8 years
- Cardiacultrasoundfor cardiac fibromas in children
- Annual X-rays for dental cysts
- Abdominal and pelvic ultrasound starting at puberty for ovarian fibromas and mesenteric cysts
- Regular complete skin examination every 2–3 months for adults, andself skin examination
- Neurological,ophthalmological, cardiac,orthopaedic, andurogynaecologicalexaminations
- Radiotherapyiscontraindicateddue to the increased risk of skin cancer
- Medulloblastoma — surgery andchemotherapy
- Basal cell carcinomas — options include:
- Small superficial BCC in non-critical sites —curettage &cautery,cryotherapy,5-fluorouracil,imiquimod,photodynamictherapy,
- Large or aggressive BCC —excision; considerMohs surgery
- Multiple BCC —electrochemotherapywithbleomycinunder sedation
- Hedgehoginhibitorssuch asvismodegib(oral) andsonidegib(topical).
- Odontogenic keratocysts —peripheralosteotomywith curettage
Basal cell naevus syndrome patients continue todevelopnew BCC throughout their life, with some patients having over 1000 BCC in their lifetime (median8). Basal cell carcinomas can be clinically aggressive causing considerablemorbidityand can be fatal. Life expectancy is generally believed to not otherwise be affected.