05/29/2025
Derm Index: A Deep Dive into Gorlin Syndrome
Nevoid Basal Cell Carcinoma Syndrome (NBCCS), also known as Basal Cell Nevus Syndrome or Gorlin Syndrome, is a rare genetic disorder primarily characterized by the early onset of multiple basal cell carcinomas (BCCs), jaw cysts, and various other abnormalities affecting the skin, bones, and central nervous system. First described by dentist R.J. Gorlin in 1960, the syndrome has since been recognized as a complex condition with a broad spectrum of clinical manifestations. Although NBCCS is most commonly inherited in an autosomal dominant manner, approximately one-third of cases arise due to spontaneous mutations. The disorder affects between 1 in 56,000 and 1 in 164,000 individuals globally, with no significant gender predilection.
Etiology and Genetic Basis
NBCCS is caused by mutations in the PTCH1 gene, located on chromosome 9q22.3, which encodes the Patched 1 receptor involved in the Hedgehog signaling pathway. This pathway plays a critical role in cellular differentiation, growth, and development. Mutations in PTCH1 result in dysregulated Hedgehog signaling, leading to abnormal cell proliferation and the formation of neoplastic lesions, particularly BCCs. While most cases are inherited, approximately one-third of patients have no family history of the condition, indicating the presence of de novo(new) mutations.
Clinical Manifestations
The hallmark of NBCCS is the development of multiple BCCs, often appearing in childhood or adolescence, in stark contrast to the typical onset of BCCs in older adults due to sun exposure. BCCs in NBCCS typically manifest in individuals as young as 3–4 years old, with patients having an average of 8 BCCs; however, some may develop hundreds or even thousands over their lifetime. The incidence of BCCs is influenced by skin type, sun exposure, and radiation history. Fair-skinned individuals are more prone to developing numerous BCCs, whereas those with darker skin tones, such as Black individuals, tend to develop fewer skin cancers.
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