NBCCS

Basal Cell Nevus Syndrome

Clinical Characteristics
Ocular Features: 

Eyelid basal-cell carcinomas are the most common ocular finding of this syndrome.  These malignancies may be multiple and may occur on the neck, chest, back, arms and elsewhere on the face.   Those on the eyelids generally have their onset in the postpubertal period, usually by age 35 years, and are often multiple.  Their indolent nature can result in considerably delay in diagnosis, however, and local recurrences are common.  Deformities of the skull often result in the appearance of hypertelorism and proptosis.  Epidermal cysts are found in one-fourth of patients, especially on the palms, but may occur in the tarsal conjunctiva as well.  Intratarsal keratinous eyelid cysts occur in 40% of patients.  Less common reported ocular findings are colobomas, glaucoma, nystagmus, strabismus, and cataracts but these may simply be associations.

Systemic Features: 

This disorder is one of a few in which a disposition to neoplasia is associated with skeletal deformities.  These include bifid ribs, scoliosis, skull deformities such as frontal bossing, increased occipitofrontal circumference, broad nasal root with hypertelorism, mandibular prognathia, and bony cysts.  Medulloblastoma is an infrequent but important sign.  Palmar and/or plantar pits are often present.  Basal cell carcinomas and jaw cysts occur in over 90% of patients by the age of 40 years.  Invasive oral tumors are found in 78% of individuals.

Genetics

This is an autosomal dominant disorder, caused by heterozygous mutations in the PTCH1 gene located on chromosome 9 (9q22.3).  Interestingly, somatic mutations in the PTCH1 gene have also been found in isolated cases with only basal cell carcinoma or medulloblastoma.  Perhaps 40% of cases arise de novo, i.e., without a family history, and older paternal age at conception increases the risk of new mutations.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Treatment is directed at the location of clinical disease with excision of basal cell carcinomas having the highest priority.  Patients must be monitored throughout life for new lesions as well as recurrence at treated sites. Radiotherapy and non-essential diagnostic X-rays should probably be avoided due to sensitivity to ionizing radiation.

Oral administration of an experimental small molecule signaling inhibitor (GDC-0449 or Vismodegib; Genetech) of the Hedgehog signaling pathway has shown promise in reduction of the number of new lesions as well as shrinkage of existing skin lesions.  BCC lesions have been successfully treated with ingenol mebutate in a single patient.

References
Article Title: 

Eyelid Cysts in Gorlin Syndrome: A Review and Reappraisal

Wolkow N, Jakobiec FA, Yoon MK. Intratarsal Keratinous Eyelid Cysts in Gorlin Syndrome: A Review and Reappraisal. Surv Ophthalmol. 2017 Dec 26. pii: S0039-6257(17)30236-9. doi: 10.1016/j.survophthal.2017.12.007.

PubMed ID: 
29287708

Basal cell nevus syndrome: a brave new world

Goldberg LH, Firoz BF, Weiss GJ, Blaydorn L, Jameson G, Von Hoff DD. Basal cell nevus syndrome: a brave new world. Arch Dermatol. 2010 Jan;146(1):17-9. PubMed PMID: 20083687.

PubMed ID: 
20083687
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