Nevoid Basal Cell Carcinoma Syndrome Panel

About Nevoid Basal Cell Carcinoma Syndrome  

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is characterized by the development of multiple jaw keratocysts typically beginning in the teenage years, and basal cell carcinomas (BCCs) that typically emerge from the third decade onward.¹ Affected individuals often present with distinctive features including macrocephaly, frontal bossing, coarse facial features, facial milia, and skeletal anomalies including bifid ribs and wedge-shaped vertebrae. Medulloblastoma, a primitive neuroectodermal tumor, may develop in approximately 5% of children with peak incidence at 1-2 years of age. The risk of developing medulloblastoma is higher in individuals with pathogenic variants in SUFU (33%) compared to PTCH1 (<2%).¹ Additional features may include cardiac fibromas (2%) and ovarian fibromas (20%). NBCCS has an estimated birth incidence of approximately 1:19,000 and is inherited in an autosomal dominant manner.² Approximately 70-80% of NBCCS cases result from a pathogenic variant inherited from an affected parent while the remaining 20-30% result from de novo pathogenic variants. NBCCS is primarily caused by pathogenic variants in genes involved in the hedgehog signaling pathway (PTCH1, SUFU, and rarely PTCH2).^1,3,4 Both sequence variants and copy number variants have been identified as causative. The diagnostic yield of genetic testing is expected to be in the range of 50-85%.¹ 

All genetic tests have limitations. Please refer to our Test Methods page for limitations relevant to this methodology. 

The analytical sensitivity of this PGSelect platform has been validated at >99% for single nucleotide variants, >95% for indels <49 bp, and >99% for CNV ≥4 exons. Sensitivity is reduced in regions with repetitive elements or paralogy. 

PGSelect platform: Capture and amplification based Next Generation Sequencing (NGS) is used to sequence the coding regions of a subset of genes from the genome which are included on this panel and immediate flanking non-coding DNA (± 10 bp) in all available transcripts along with other non-coding regions harboring known disease-causing variants. Results are filtered to defined genes in panel. Reportable variants include both sequence variants and NGS-based detection of copy number variants (CNVs). Variants not meeting our quality threshold through NGS alone are confirmed with an orthogonal method, including but not limited to Sanger and array. All variants within the analyzed genes which are classified as pathogenic, likely pathogenic, risk, or variant of uncertain significance will be reported.