Gorlin–Goltz Syndrome: A Case Report and Literature Review with PTCH1 Gene Sequencing

Abstract

Gorlin–Goltz syndrome, also known as nevoid basal cell carcinoma syndrome, is an autosomal dominant disease characterized by multisystemic developmental defects caused by pathogenic variants such as patched-1 (PTCH1) gene variants and/or SUFU gene variants. The presence of either two main criteria or one major and two minor criteria are required for the diagnosis of Gorlin–Goltz syndrome. Recently, a major criterion for molecular confirmation has also been proposed. In this article, we report the case of an 80-year-old male who was admitted at our department for multiple brown-to-black papules and plaques on the entire body. He was diagnosed with Gorlin–Goltz syndrome with clinical, radiologic, and pathologic findings. While the diagnosis was made based on the clinical findings in general, confirmation of the genetic variants makes an ideal diagnosis and suggests a new treatment method for target therapy. We requested a genetic test of PTCH1 to ideally identify the molecular confirmation in the hedgehog signaling pathway. However, no pathogenic variants were found in the coding region of PTCH1, and no molecular confirmation was achieved.

Keywords

Gorlin–Goltz syndrome - PTCH1 gene - basal cell carcinoma syndrome

Patient consent

The patient provided written informed consents for the publication and the use of patient's images.

Authors' Contributions

Conceptualization: H.S.K. Data curation: S.H. Supervision: H.S.K. Validation: H.S.K. Writing – original draft: S.H. and H.S.K. Writing – review & editing: H.S.K., K.S.K., J.Y.Y, J.C., and S.H. All authors read and approved the final manuscript.

Publication History

Received: 14 May 2022

Accepted: 10 May 2023

Accepted Manuscript online:
19 May 2023

Article published online:
02 August 2023

• Reference

• 1 Bresler SC, Padwa BL, Granter SR. Nevoid basal cell carcinoma syndrome (Gorlin syndrome). Head Neck Pathol 2016; 10 (02) 119-124
• 2 Ortega García de Amezaga A, García Arregui O, Zepeda Nuño S. et al. Gorlin-Goltz syndrome: clinicopathologic aspects. Med Oral Patol Oral Cir Bucal 2008; 13: 338-343
• 3 Şereflican B, Tuman B, Şereflican M, Halıcıoğlu S, Özyalvaçlı G, Bayrak S. Gorlin-Goltz syndrome. Turk Pediatri Ars 2017; 52 (03) 173-177
• 4 Kumar NN, Padmashree S, Jyotsna TR, Shastry SP. Gorlin-Goltz syndrome: a rare case report. Contemp Clin Dent 2018; 9 (03) 478-483
• 5 Onodera S, Nakamura Y, Azuma T. Gorlin syndrome: Recent advances in genetic testing and molecular and cellular biological research. Int J Mol Sci 2020; 21 (20) 7559
• 6 Bree AF, Shah MR. BCNS Colloquium Group. Consensus statement from the first international colloquium on basal cell nevus syndrome (BCNS). Am J Med Genet A 2011; 155A [phone]
• 7 Johnson RL, Rothman AL, Xie J. et al. Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science 1996; 272 (5268): 1668-1671
• 8 Atwood SX, Chang ALS, Oro AE. Hedgehog pathway inhibition and the race against tumor evolution. J Cell Biol 2012; 199 (02) 193-197
• 9 Varjosalo M, Taipale J. Hedgehog: functions and mechanisms. Genes Dev 2008; 22 (18) 2454-2472
• 10 Cherry AL, Finta C, Karlström M. et al. Structural basis of SUFU-GLI interaction in human Hedgehog signalling regulation. Acta Crystallogr D Biol Crystallogr 2013; 69 (Pt 12): 2563-2579
• 11 Klein RD, Dykas DJ, Bale AE. Clinical testing for the nevoid basal cell carcinoma syndrome in a DNA diagnostic laboratory. Genet Med 2005; 7 (09) 611-619
• 12 Morita K, Naruto T, Tanimoto K. et al. Simultaneous detection of both single nucleotide variations and copy number alterations by next-generation sequencing in gorlin syndrome. PLoS One 2015; 10 (11) e0140480
• 13 Manfredi M, Vescovi P, Bonanini M, Porter S. Nevoid basal cell carcinoma syndrome: a review of the literature. Int J Oral Maxillofac Surg 2004; 33 (02) 117-124
• 14 Samela PC, Tosi V, Cervini AB, Bocian M, Buján MM, Pierini AM. Nevoid basal cell carcinoma syndrome: our experience in a pediatric hospital. Actas Dermosifiliogr 2013; 104 (05) 426-433
• 15 Stojanov IJ, Schaefer IM, Menon RS. et al. Biallelic PTCH1 Inactivation Is a Dominant Genomic Change in Sporadic Keratocystic Odontogenic Tumors. Am J Surg Pathol 2020; 44 (04) 553-560
• 16 Gutzmer R, Solomon JA. Hedgehog Pathway Inhibition for the Treatment of Basal Cell Carcinoma. Target Oncol 2019; 14 (03) 253-267
• 17 Axelson M, Liu K, Jiang X. et al. U.S. Food and Drug Administration approval: vismodegib for recurrent, locally advanced, or metastatic basal cell carcinoma. Clin Cancer Res 2013; 19 (09) 2289-2293
• 18 Parren LJMT, Frank J. Hereditary tumour syndromes featuring basal cell carcinomas. Br J Dermatol 2011; 165 (01) 30-34