title: Multiple nevoid basal cell carcinoma syndrome associated with congenital orbital teratoma, caused by a PTCH1 frameshift mutation.
abstract: Gorlin-Goltz syndrome, or nevoid basal cell carcinoma syndrome (NBCCS), is a rare autosomal dominant disorder caused by mutations in the PTCH1 gene and shows a high level of penetrance and variable expressivity. The syndrome is characterized by developmental abnormalities or neoplasms and is diagnosed with 2 major criteria, or with 1 major and 2 minor criteria. Here, we report a new clinical manifestation associated with this syndrome in a boy affected by NBCCS who had congenital orbital teratoma at birth. Later, at the age of 15 years, he presented with 4 major and 4 minor criteria of NBCCS, including multiple basal cell carcinoma and 2 odontogenic keratocysts of the jaw, both confirmed by histology, more than 5 palmar pits, calcification of the cerebral falx, extensive meningeal calcifications, macrocephaly, hypertelorism, frontal bosses, and kyphoscoliosis. PTCH1 mutation analysis revealed the heterozygous germline mutation c.290dupA. This mutation generated a frameshift within exon 2 and an early premature stop codon (p.Asn97LysfsX43), predicting a truncated protein with complete loss of function. Identification of this mutation is useful for genetic counseling. Although the clinical symptoms are well-known, our case contributes to the understanding of phenotypic variability in NBCCS, highlighting that PTCH1 mutations cannot be used for predicting disease burden and reinforces the need of a multidisciplinary team in the diagnosis, treatment, and follow-up of NBCCS patients.
authors.affiliation: Serviço de Pediatria, Hospital do Divino Espírito Santo de Ponta Delgada, EPE, Açores, Portugal.
authors.forename: A L
authors.initials: AL
authors.lastname: Rodrigues
authors.affiliation: Serviço de Pediatria, Hospital do Divino Espírito Santo de Ponta Delgada, EPE, Açores, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Carvalho
authors.affiliation: Unidade de Genética e Patologia Moleculares, Hospital do Divino Espírito Santo de Ponta Delgada, EPE, Açores, Portugal.
authors.forename: R
authors.initials: R
authors.lastname: Cabral
authors.affiliation: Serviço de Anatomia Patalógica, Hospital do Divino Espírito Santo de Ponta Delgada, EPE, Açores, Portugal.
authors.forename: V
authors.initials: V
authors.lastname: Carneiro
authors.affiliation: LabGenetics, Laboratorio de Genetica Clinica S.L. San Sebastián de los Reyes, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Gilardi
authors.affiliation: Serviço de Pediatria, Hospital do Divino Espírito Santo de Ponta Delgada, EPE, Açores, Portugal.
authors.forename: C P
authors.initials: CP
authors.lastname: Duarte
authors.affiliation: LabGenetics, Laboratorio de Genetica Clinica S.L. San Sebastián de los Reyes, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Puente-Prieto
authors.affiliation: Serviço de Dermatologia, Hospital do Divino Espírito Santo de Ponta Delgada, EPE, Açores, Portugal.
authors.forename: P
authors.initials: P
authors.lastname: Santos
authors.affiliation: Unidade de Genética e Patologia Moleculares, Hospital do Divino Espírito Santo de Ponta Delgada, EPE, Açores, Portugal Luisa.MQ.Vieira@azores.gov.pt.
authors.forename: L
authors.initials: L
authors.lastname: Mota-Vieira
mesh_terms: D000293:Adolescent; D001478:Basal Cell Nevus Syndrome / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D001921:Brain / Q000473:pathology; D002280:Basal Cell Carcinoma / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D016368:Frameshift Mutation; D018095:Germ-Line Mutation; D006223:Hamartoma Syndrome, Multiple / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D009918:Orbital Neoplasms / Q000151:congenital / Q000175:diagnosis / Q000209:etiology*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011862:Radiography, Panoramic; D011956:Receptors, Cell Surface / Q000235:genetics*; D013724:Teratoma / Q000151:congenital / Q000175:diagnosis / Q000209:etiology*; D014057:Tomography, X-Ray Computed
chemical_list: C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface