Basal cell nevus syndrome (Gorlin-Goltz syndrome): genetic predisposition, clinical picture and treatment

Gorlin-Goltz syndrome (Online Mendelian Inheritance in Man, MIM, 109400), also called nevoid basal cell carcinoma syndrome (BCCS) or basal cell nevus syndrome (BCNS), is a multisystemic autosomal dominant disorder with a high penetrance and variable expressiveness [1]. The classical triad is composed of multiple basal cell carcinomas, keratocystic odontogenic tumors and bifid ribs. The disease is variably associated with other neurological, ophthalmic, endocrine and genital manifestations, with onset during the first, second and third decades of life [2]. The estimated prevalence is 1/60,000 and varies from 1/30 827 to 1/256 000 [3, 4]. It affects males and females equally and arises in all ethnic groups, but most of reported cases are in whites [5].
The genodermatosis is caused in most cases by heterozygous mutations in tumor suppressor gene PTCH, located on chromosome 9q22.3 [6]. Molecular germline mutations in BCNS include frameshift, nonsense, missense and splicing mutations, exonic, multi-exonic or rearrangements [7]. The PTCH1 gene encodes a transmembrane glycoprotein that acts as the antagonist receptor for the sonic hedgehog ligand in the hedgehog and smoothened (SMO) signaling pathways [8]. Hedgehog and SMO signaling pathways regulate cell growth and development and thus their disruption results in developmental anomalies and tumors [9]. Up to 60% of patients can suffer from BCNS resulting from de novo mutations [10].
In overall, the disorder comprises five prevalent clinical manifestations: multiple nevoid BCCS, keratocystic odontogenic tumors (KOT), skeletal anomalies, lamellar calcification of falx cerebri and palms and/or plantar pits [11]. A detailed list of diverse clinical features in BCNS is displayed in Table 1 and comprises developmental anomalies together with tumors.
Developmental defects in BCNS include craniofacial anomaly, together with anomalies of the neurological system, axial skeleton, hands and feet. A characteristic coarse facial appearance includes frontal and temporal bossing, high and broad forehead, well-developed supraorbital ridges, hypertelorism, broad nasal root and wide nasal bridge, mandibular prognathism, internal strabismus and rotatory nystagmus [12, 13]. The symptoms can be associated with hypoplastic maxilla and crossbite teeth relationship, high arched palate, cleft lip and palate, malocclusion and impacted teeth [12]. Macrocephaly is present at birth and is often associated with cerebral...


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