Gorlin-Goltz syndrome – a medical condition requiring a multidisciplinary approach

Abstract

SummaryGorlin-Goltz syndrome is a rare genetic condition showing a variable expressiveness. It is inherited in a dominant autosomal way. The strongest characteristic of the disease includes multiple basal cell carcinomas, jaw cysts, palmar and plantar pits, skeletal abnormalities and other developmental defects. Owing to the fact that the condition tends to be a multisystemic disorder, familiarity of various medical specialists with its manifestations may reduce the time necessary for providing a diagnosis. It will also enable them to apply adequate methods of treatment and secondary prevention. In this study, we present symptoms of the disease, its diagnostic methods and currently used treatments.We searched 2 scientific databases: Medline (EBSCO) and Science Direct, for the years 1996 to 2011. In our search of abstracts, key words included nevoid basal cell carcinoma syndrome and Gorlin-Goltz syndrome.We examined 287 studies from Medline and 80 from Science Direct, all published in English. Finally, we decided to use 60 papers, including clinical cases and literature reviews.Patients with Gorlin-Goltz syndrome need particular multidisciplinary medical care. Knowledge of multiple and difficult to diagnose symptoms of the syndrome among professionals of various medical specialties is crucial. The consequences of the disease pose a threat to the health and life of patients. Therefore, an early diagnosis creates an opportunity for effective prevention and treatment of the disorder. Prevention is better than cure.

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

“…This case increases the understanding of phenotypic variability and highlights that PTCH1 mutations cannot be used to predict disease burden. In addition, our results reinforce the role of a multidisciplinary team in the diagnosis, treatment, and follow-up of GorlinGoltz syndrome patients, as recently proposed by Kiwilsza and Sporniak-Tutak (2012).…”

Hypomorphic Recessive Variants in SUFU Impair the Sonic Hedgehog Pathway and Cause Joubert Syndrome with Cranio-facial and Skeletal Defects

“…23 Moreover, a proportion of subjects with Gorlin syndrome, caused by heterozygous loss-of-function variants of either PTCH1 or SUFU, variably exhibit macrocephaly, hypertelorism, depressed nasal bridge, post-axial polydactyly, as well as macrosomia and dyskeratotic plantar pits (present in family COR369). 24 These observations suggest that these peculiar cranio-facial and digit anomalies are strictly related to abnormal activation of the SHH pathway, caused either by reduced levels (or functioning) of repressor proteins or by the constitutive activation of proteins that transduce SHH signaling. Conversely, genetic changes impairing activation of the SHH pathway, such as heterozygous variants of SHH or GLI2, are consistently associated with opposite cranio-facial dysmorphisms such as microcephaly, hypotelorism, microphthalmia, midface hypoplasia, and cleft lip/palate, that variably associate with forebrain cleavage anomalies (defining the holoprosencephaly spectrum) and digital number abnormalities.…”

“…Germline heterozygous loss-of-function variants of either PTCH1 or SUFU (MIM: 607035) may cause a complex condition termed nevoid-basal-cell carcinoma syndrome (Gorlin syndrome [MIM: 109400]), characterized by the occurrence of several basal cell carcinomas and other cancers at a young age (<20 years), variably associated with developmental and skeletal abnormalities. 24,25 Moreover, somatic variants of PTCH1 or SMO, and both germinal and somatic variants of SUFU, have been found to predispose to a variety of tumors, such as basal cell carcinoma, meningioma, and cerebellar medulloblastoma (MIM: 605462, 607174, 155255). [26][27][28][29][30] To date, germline recessive pathogenic variants of SUFU have never been reported in human subjects, supporting the essential role of SUFU in embryonic development.…”

Cohort study of Gorlin syndrome with emphasis on standardised phenotyping and quality of life assessment

“…Gorlin syndrome, also known as the nevoid basal cell carcinoma syndrome (NBCCS), is an autosomal dominant developmental syndrome, which causes various congenital abnormalities and a predisposition to basal cell carcinomas (BCC) . The condition is highly penetrant; however, the clinical features can be variable . The Australian prevalence, ascertained on clinical criteria, was estimated to be 1:164 000 in 1994 …”