Gorlin-Goltz syndrome: Case report

Gorlin-Goltz syndrome, also known as basal cell nevus syndrome, is an uncommon, autosomal dominant inherited disorder, which is characterized by numerous basal cell carcinomas, maxillary keratocysts, and musculoskeletal malformations. Occasionally, it is associated with aggressive basal cell carcinomas and internal malignancies. Early diagnosis and treatment are essential, as well as genetic counseling. A patient with characteristic symptoms of nevoid basal cell carcinoma and a review of the literature is presented.


Introduction
Gorlin-Goltz syndrome, also known as basal cell nevus syndrome, is an uncommon, autosomal dominant inherited disorder, which is characterized by numerous basal cell carcinomas (seen in 50-97% of people with the syndrome), maxillary keratocysts (present in about 75% of patients) and musculoskeletal malformations. It was first reported by Jarisch and White in 1894. Binkley and Johnson in 1951, and Howell and Caro in 1959 suggested a relationship between basal cell epitheliomas and developmental malformations. Robert J.Gorlin and Robert W. Goltz described the distinct syndrome, consisting of the presence of multiple nevoid basal cell epitheliomas, jaw cysts, and bifid ribs 1 . The incidence of this disorder is estimated to be 1 in 50,000 to 150,000 in the general population, varying by region 2 . It appears in all ethnic groups, but most often in whites; males and females are equally affected 3 . Along with multiple basal cell carcinomas (BCC), jaw cysts and musculoskeletal anomalies are lesser known manifestations of this disorder involving the skin, central nervous system, ophthalmic, endocrine, urogenital system, and so on 4-7 .

Case report
We present a 74-year-old male patient came to opd with complaints of ulcer over right side of face and blackish lesion over medial angle of left eye ( Figure.1). He had skin changes, predominantly on photo exposed areas, allegedly starting 1 year ago. Patient gave history of similar ulcer of which wide excision was done 2 years ago. The examination revealed numerous (over 50) papules and nodes predominantly on his face, but also on the skin of the chest and back, up to 1 cm in diameter ( Figure. 1). The skin of his palms and soles was hyperkeratotic with tiny pits. Inspection revealed a coarse face with dense, fused eyebrows, and frontal prominences. Radiographic examination showed a calcified falx cerebri. No other bony anomalies were observed.

Figure 1: Presentation of Patient in our clinic
Routine laboratory tests were normal. Ultrasound examination of the abdomen did not show any abnormalities. Histopathologic examination of a nodule excised from the angle of eye and ulcer confirmed the diagnosis of basal cell carcinoma, and we established the diagnosis of Gorlin-Goltz syndrome. Our patients elder brother had history of similar pigmented papules over face ( Figure 2). Patient underwent wide surgical excision with primary closure for both lesions (Figure 3). Histopathology confirmed basal cell carcinoma. We insisted on regular checks-ups.

Discussion
Gorlin-Goltz syndrome is autosomal dominant with a high penetrance and variable expressivity. It is causedby mutations in the patched tumor suppressor gene (PTCH), a human homologue of the Drosophila genemapped to chromosome 9q21-23 1,4 . Chromosomal mapping and genetic studies suggest that the underlying basis for this disease is an abnormality in the Hedgehog (Hh) signaling pathway. The role of this pathway in embryogenesis is well known. The PTCH gene product is part of a receptor for the protein called Sonic Hedgehog (SHH), which is involved in embryonic development 8  Other diagnostic findings in adults with Gorlin-Goltz syndrome are: I. Skeletal anomalies: Hemivertebrae, scoliosis, syndactyly, polydactyly, shortened 4th metacarpal.
V. Anomalies of the reproductive system VI. Cardiac anomalies Tumors accompanying this syndrome include parathyroid adenoma, adrenal cystic lymphangioma, ovarian fibroma, and other neoplasms. This syndrome is followed by multiple complications, predominantly aggressive basal cell tumors invading surrounding structures, or distant metastases, causing death. Medulloblastoma causes death during infancy. Recurrence of odontogenic keratocysts causes varying degrees of jaw deformity.
Diagnosis and therapy of this syndrome require a multi disciplinary approach (dermatologists, surgeons, dentists, maxillary surgeons, and neurologists). It consists of removal of tumors (surgical excision, topical chemotherapies, and laser ablation) and adequate treatment of maxillary cysts. A new treatment strategy, based on the understanding of the Hh signaling pathway and the premise that tumors arise due to it's over activity, supposes that inhibition of this pathway with specific pharmacological treatment might suppress tumor growth 1 .
Patients with Gorlin-Goltz syndrome require consistent sun protection. Genetic counseling that considers the genetic risks is advisable for all patients with this syndrome, both familial and sporadic.