“ PTCH ”-ing It Together: A Basal Cell Nevus Syndrome Review

Abstract

Adolescents and young adults with BCC should be evaluated for BCNS. Early diagnosis of BCNS is critical for possible prevention of the devastating effects of BCCs and establishment of multidisciplinary care.

New mutations and an updated database for the patched‐1 (PTCH1) gene

“…Recent mouse model studies show that haploinsufficiency of PTCH1 may be sufficient for the development of medulloblastoma and rhabdomyosarcoma, so tumor formation not always follows the two‐hit hypothesis (Calzada‐Wack et al., ; Zurawel, Allen, Wechsler‐Reya, Scott, & Raffel, ). With DNA sequencing analysis of the PTCH1 gene, mutation detection frequency ranges from 50% to 85% in individuals with typical findings of BCNS (Lam, Ou, & Billingsley, ). Mosaic presentations of BCNS can occur (Reinders et al., ; Torrelo et al., ).…”

A 9‐Year‐Old Girl with Pearly Skin Colored Papules with Palmar Pits

“…A diagnosis of BCNS should be considered when a patient has one major criterion and molecular confirmation, two major criteria, or one major and two minor criteria . The prevalence of BCNS is estimated to be between 1 in 19,000 and 1 in 256,000, and BCNS affects both sexes and various cultural groups .…”

“…Mutations in the sonic hedgehog (SHH) pathway cause BCNS, most commonly with inactivating mutations in the PATCHED1 ( PTCH1 ) tumor suppressor gene at chromosome 9q22.3 . PTCH1 encodes a surface membrane receptor (PTCH1) that normally suppresses the activation of the transmembrane protein smoothened (SMO) .…”

“…Mutations in the sonic hedgehog (SHH) pathway cause BCNS, most commonly with inactivating mutations in the PATCHED1 ( PTCH1 ) tumor suppressor gene at chromosome 9q22.3 . PTCH1 encodes a surface membrane receptor (PTCH1) that normally suppresses the activation of the transmembrane protein smoothened (SMO) . SHH signaling is essential for the establishment of normal body and limb patterning, but in BCNS, the inactivating mutation in PTCH1 results in unregulated stimulation of SHH signaling due to loss of SMO suppression.…”

“…SHH signaling is essential for the establishment of normal body and limb patterning, but in BCNS, the inactivating mutation in PTCH1 results in unregulated stimulation of SHH signaling due to loss of SMO suppression. This ultimately leads to abnormal proliferation and carcinogenesis . Individuals with BCNS inherit one defective PTCH1 allele and acquire a ‘second hit’ from external factors such as radiation and ultraviolet (UV) light, leading to tumorogenesis .…”