|Year : 2021 | Volume
| Issue : 4 | Page : 119-123
Deciphering a rare genetic entity: A case report on Gorlin–Goltz syndrome
Sooraj Soman1, Tom Thomas1, Sachin Aslam1, Reshma Rajasekhar2, Kiran Vincent1, Sajeesh Raj1
1 OMFS, MES Dental College, Kerala, India
2 Endodontics, MES Dental College, Kerala, India
|Date of Submission||22-Jun-2021|
|Date of Acceptance||27-Aug-2021|
|Date of Web Publication||27-Dec-2021|
Dr. Sooraj Soman
MES Dental College, Kerala.
Source of Support: None, Conflict of Interest: None
Gorlin–Goltz syndrome (nevoid basal cell carcinoma syndrome) is a rare autosomal dominant disorder caused due to mutation in the PTCH (patched gene) located in the arm of the ninth chromosome. The disease is characterized by increased incidence for nevoid basal cell carcinoma and other multi-organ disorders including multiple odontogenic keratocysts. Early diagnosis and stringent follow-up are necessary for preventing untoward consequences of the disease. This case report emphasizes on the necessity of adhering to proposed criteria and need for thorough investigation to rule out central nervous system lesions in the patients.
Keywords: Gorlin–Goltz syndrome, nevoid basal cell carcinoma, odontogenic keratocyst
|How to cite this article:|
Soman S, Thomas T, Aslam S, Rajasekhar R, Vincent K, Raj S. Deciphering a rare genetic entity: A case report on Gorlin–Goltz syndrome. Int J Oral Care Res 2021;9:119-23
|How to cite this URL:|
Soman S, Thomas T, Aslam S, Rajasekhar R, Vincent K, Raj S. Deciphering a rare genetic entity: A case report on Gorlin–Goltz syndrome. Int J Oral Care Res [serial online] 2021 [cited 2022 Jan 19];9:119-23. Available from: https://www.ijocr.org/text.asp?2021/9/4/119/333810
| Introduction|| |
Gorlin–Goltz syndrome (GGS) also known as nevoid basal cell carcinoma syndrome is a rare autosomal dominant genetic disorder with variable expressions and complete penetration. The prevalence of the condition varies from 1:57,000 to 1:256,000 with an equal male to female ratio.,
In 1894, Jarisch and White first reported the syndrome in a patient with scoliosis, multiple basocellular carcinoma, and learning disability. Binkley and Johnson in 1951 and Howell and Caro in 1959 suggested the relationship between development malformations and basocellular epitheliomas. In 1960, Robert James Gorlin and William Goltz gave its classical triad (multiple basocellular epitheliomas, keratocysts in jaws, and bifid ribs) that determined the diagnosis.,
The pathogenesis of GGS is attributed to the loss of a tumor suppressor gene known as the human patched gene (PTCH1 gene). This gene is important for embryonic structuring and cellular cycle; hence, its mutation can lead to certain developmental abnormalities and neoplasms.
Diagnostic criteria for GGS were introduced by Evans et al. in 1993 and modified by Kimonis et al. in 1997 and Bree et al. in 2011. Major criteria include nevoid basal cell carcinomas, odontogenic keratocysts, palmar or plantar pitting, lamellar calcification of the falx cerebri, and medulloblastoma. Minor criteria include rib anomalies, skeletal malformations and radiologic changes (vertebral anomalies, kyphoscoliosis, etc.), macrocephaly, cleft lip and/or palate, ovarian/cardiac fibroma, lympho-mesenteric cysts, and ocular abnormalities (i.e., hypertelorism, congenital cataracts, glaucoma, etc.). Diagnosis of GGS can be made in the presence of two major criteria or one major criterion with molecular confirmation or one major and two minor criteria.
The condition requires early detection and thorough follow-up as it may have fatal outcomes such as multiple skin cancers and other tumors. Our case emphasizes on the early and accurate detection of the condition to minimize fatal consequences.
| Case Report|| |
A 23-year-old female patient reported to our maxillofacial unit with a chief complaint of pain and swelling in the right upper back tooth region since 6 months. Pain was intermittent and dull aching in nature. The swelling was initially small and has gradually increased to create an asymmetry of the right midface region. There was no relevant medical history. She gave a history of cyst enucleation in the right mandible 9 years before. She also gave a history of root canal treatment of the upper right first molar in the last month.
The patient gives a familial history wherein her mother (right mandible) and elder sister had undergone surgery for a similar swelling. Biopsy report of her mother revealed a diagnosis of parakeratinized odontogenic keratocyst, whereas elder sister was diagnosed with dysgenetic polycystic disease of parotid.
General physical examination revealed broadening of alar base, frontal bossing, and palmar and plantar pits [Figure 1] and on extraoral examination, diffused swelling was noted on the right middle third of face extending 2 cm anterior to the right tragus of the ear to ala of the nose antero-posteriorly and from the right zygomatic arch up to the corner of the mouth supero-inferiorly. The swelling was approximately 2 × 2.5 cm in size. Intraorally, a vestibular swelling was noted from 15 to 17. The swelling was tender and firm in consistency with a positive “egg shell cracking” sign along the region of buccal cortical bone expansion.
Orthopantomogram (OPG) revealed two radiolucent lesions in maxilla and one in the left ramus of the mandible. In the right maxilla, the lesion was located in the periapical region of premolars with an impacted canine within the lesion. In the left maxilla, the lesion was located periapical to the molars with two impacted supernumerary teeth in which one located far superiorly close to the infraorbital rim. In mandible, there was a mixed radiopaque and radiolucent lesion with ground glass appearance that was located in the upper border of the ramus-angle region. The axial computed tomography (CT) of the jaws revealed three osteolytic lesions: two in maxilla and one in mandible with areas of ground glass appearance. CT scan of brain showed lamellar calcification in the falx and tentorium cerebelli [Figure 2]. Chest X-ray showed bifurcation of anterior end of third rib [Figure 3].
|Figure 2: (a) Axial CT showing osteolytic lesions. (b) CT brain bone window showing falx cerebri calcification. (c) OPG revealing multiple radiolucent lesions in the maxilla and mandible with multiple impacted tooth|
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|Figure 3: Chest X-ray anteroposterior view showing presence of a bifid third rib in the right anterior end|
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An incisional biopsy was performed on the lesion from the maxilla. Histopathological examination revealed parakeratinized stratified squamous epithelium with palisading pattern of columnar cells interspersed with giant cells and keratin pearls.
The patient underwent surgical enucleation of the lesion along with chemical cauterization using Carnoy’s solution. Histopathological examination of the lesion confirmed the diagnosis of multiple odontogenic keratocysts. Based on clinical, radiological, and histological examination and referring to the diagnostic criteria established by Evans et al. and modified by Kimonis et al., a diagnosis of GGS was made [Figure 4].
|Figure 4: (a) Intra-operative picture showing cyst enucleation and removal of tooth associated with the cystic lining. (b) Gross macroscopic picture of excised surgical specimen with associated impacted tooth. (C) Histopathology showing characteristic odontogenic keratinized cystic lining with palisaded hypochromatic basal cells|
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| Discussion|| |
GGS is an infrequent autosomal dominant genetic entity. Causality of GGS is linked to a tumor suppressor gene called as the patched gene (PTCH) located in the 9q22.3 chromosome. It demands an early recognition as these patients are more prone to multiple malignant neoplasms of skin and brain and are sensitive for ionizing radiation such as ultraviolet radiation. The diagnostic criteria for the GGS were given by Evans et al. and were modified by Kimonis et al. in 1997 and are established by major and minor clinical and radiological criteria and are confirmed by DNA analysis., It states that two major or one major with two minor criteria are required for the diagnosis of GGS. The criteria are described below.
Our case displayed four major criteria (multiple odontogenic keratocyst, palmar and plantar pits, and calcification of falx cerebri) and hence was diagnosed as GGS.
The odontogenic keratocysts found in the syndromic cases are different from those found in the sporadic cases both histologically and immunochemically. The syndromic cases occur relatively at a younger age group and have a greater number of satellite cysts, proliferating solid epithelial islands, presence of odontogenic rests within the capsule, and mitotic figures within the lining when compared with the latter.
The treatment of the GGS pertains to primarily the management of the keratocysts. It can be removed by surgical excision, laser ablation, photodynamic therapy, and topical chemotherapy (Carnoy’s solution) or a combination of the above. Recurrence rate has been found to be about 60% and may require additional surgical interventions. Mortality is rare and commonly occurs from development of medulloblastoma (5–10%) necessitating neurosurgical intervention. Recent advances of DNA mutation analysis can be useful in the antenatal detection of GGS.
Researchers have found out the presence of overactivity of sonic hedgehog (Hh pathway) in odontogenic keratocysts. Pharmacological agents targeting this pathway can be useful in suppressing the cystic transformation.
| Conclusion|| |
This case illustrates the need for proper evaluation and clinical characterization of the GGS for accurate diagnosis and management of the condition. Regular follow-up is required to identify the ongoing sequalae of GGS such as recurrent odontogenic keratocysts and basal cell carcinomas (at least 3-4 times/year). In cases with familial predisposition for the disease, the need for genetic counseling should be mandated for improving the overall survival of the patient. Although it is a disease that renders minimal mortality to the affected, the morbidity caused can be reduced if an early intervention is rendered.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]