OMIM ID:
Basal Cell Nevus Syndrome
Alternate Names
Defective Genes
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
Inheritance
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
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission