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Genet Mol Res. 2014 Jul 25;13(3):5654-63. doi: 10.4238/2014.July.25.21.

Multiple nevoid basal cell carcinoma syndrome associated with congenital orbital teratoma, caused by a PTCH1 frameshift mutation.

Author information

1
Serviço de Pediatria, Hospital do Divino Espírito Santo de Ponta Delgada, EPE, Açores, Portugal.
2
Unidade de Genética e Patologia Moleculares, Hospital do Divino Espírito Santo de Ponta Delgada, EPE, Açores, Portugal.
3
Serviço de Anatomia Patalógica, Hospital do Divino Espírito Santo de Ponta Delgada, EPE, Açores, Portugal.
4
LabGenetics, Laboratorio de Genetica Clinica S.L. San Sebastián de los Reyes, Madrid, Spain.
5
Serviço de Dermatologia, Hospital do Divino Espírito Santo de Ponta Delgada, EPE, Açores, Portugal.
6
Unidade de Genética e Patologia Moleculares, Hospital do Divino Espírito Santo de Ponta Delgada, EPE, Açores, Portugal Luisa.MQ.Vieira@azores.gov.pt.

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.

PMID:
25117323
DOI:
10.4238/2014.July.25.21
[Indexed for MEDLINE]
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