Gorlin–Goltz Syndrome: An Incidental Finding of a Rare Entity

Abstract

Gorlin–Goltz syndrome (GGS) is a rare hereditary disease characterized by multiple basal cell carcinomas, odontogenic keratocyst (OKCs) and musculoskeletal malformations. Pathogenesis of the syndrome is attributed to abnormalities in the long arm of chromosome 9 (q22.3–q31) and mutations in the human patched gene (PTCH1 gene). Here, we report a rare case of an incidental finding of GGS in an 18-year-old male patient presenting multiple OKCs, calcification of the falx cerebri, and bifid rib.

Introduction

Gorlin–Goltz syndrome (GGS) also known as nevoid basal cell carcinoma syndrome (NBCCS) is a disease of an autosomal dominant inherited pattern [1]. It was first described in 1894 by Jarisch and White as a syndrome presenting multiple basocellular carcinomas. Later in the 1960’s, Gorlin and Goltz established a classical characteristic triad of diagnosing this syndrome i.e., multiple basocellular epitheliomas, keratocysts in the jaws, and bifid ribs [2]. The incidence is estimated to be 1 in 50,000–1,50,000 in the general population, varying by region [3]. It is reported to appear in all ethnic groups, but most often affects the whites; males and females are equally affected [4]. Its clinical features arise in the 1st to 3rd decades of life, affecting multiple organ systems which include skeletal, ophthalmic, skin, reproductive, and neurological abnormalities, although all the features are rarely observed in a single patient [5].

The pathogenesis of GGS is attributed to abnormalities linked to the long arm of chromosome 9 (q22.3–q31) [1]. It has been reported that the loss of human patched gene (PTCH1 gene), which is a tumor suppressor gene, could be the molecular origin of the syndrome. PTCH1 gene is significantly responsible for the embryonic structuring and cellular cycle; thus, its mutation may lead to the development of this syndrome [6].

This article describes an Incidental finding of a rare case of GGS in an 18-year-old male patient at our hospital.

Case Report

An 18-years old male patient reported to the Department of Oral Medicine and Radiology with the chief complaint of pain in the lower left back teeth region for 2 days (Fig. 1). The patient gave a history of similar pain a few months back. A general physical examination revealed a well-oriented young boy with no evident extra-oral findings. Polydactyly was noted in the right hand (Fig. 2).

Fig. 1.

Intra-Oral image showing a carious tooth i.r.t 36

Fig. 2.

Polydactyly in the right hand

On intra-oral examination, a carious tooth i.r.t 36 was tender on vertical percussion. A high-arched palate was present. No other intra-oral abnormality was noted. On the basis of clinical examination, a provisional diagnosis of Apical Periodontitis was given and an Intra-oral periapical radiograph (IOPAR) of the involved tooth was advised. The IOPAR revealed radiolucency involving the pulp and a radiolucency with a corticated margin in the periapex of both roots. Further, an Orthopantomograph and then a CBCT was advised (Fig. 3).

Fig. 3.

Orthopantomograph revealing osteolytic lesions on the right side of the maxilla and on the bilateral sides of the mandible. Root resorption is seen i.r.t 38 and 47. Mesio-angularly impacted tooth i.r.t 48

CBCT revealed multiple multilocular well-defined radiolucency with sclerotic borders located on the right side of the maxilla and both sides of the mandible. The roots of 38 and 47 were completely involved with significant resorption. 48 was mesio-angularly placed and the inferior nerve canal appeared to be displaced inferiorly. Multiple cysts in the jaw raised suspicion of Gorlin–Goltz syndrome, so other relevant investigations were done (Fig. 4).

Fig. 4.

Image showing CBCT reconstruction of the lesions of the jaw

A CBCT scan of the axial section of the skull showed calcification of the falx cerebri. PA-Chest radiograph showed bifid 4th rib on the left side. Skin lesions like basal cell nevus or keratosis were absent (Fig. 5).

Fig. 5.

A Chest radiograph showing the presence of a bifid rib on the left side. B Computed tomography scan of the skull showing calcification of the falx cerebri

On FNAC, white cheesy material was aspirated. FNAC smears showed plenty of squamous cells with benign nuclei and abundant eosinophilic cytoplasm. Keratinous debris, mild inflammation, and multinucleated giant cells were also seen in the background (Fig. 6).

Fig. 6.

Photomicrograph showing a cystic lumen lined by wavy para-keratinized epithelium of uniform thickness supported by connective tissue capsule. The lumen is seen filled with keratin debris

The cyst enucleation was done under general anesthesia via an intra-oral approach. Carnoy’s solution (2.5%) was then applied using cotton rolls for a period of 5 min. The excess solution was then irrigated using saline and the cavity was packed with bismuth iodine paraffin paste. The pack was removed after 7 days and regular irrigation of the cavity was done. The cyst was enucleated from all the involved quadrants followed by extraction of 36, 38, 47, and 48. After the cystic lesions were enucleated, large areas of bone loss were seen and the displaced permanent teeth were splinted with a ligature wire. The enucleated cystic lining was sent for histopathological examination. Follow-up was done up to 6 months.

On microscopy, the cystic lumen was lined by wavy para-keratinized epithelium of uniform thickness supported by connective tissue capsule. The lumen is filled with keratin debris. There was no evidence of granuloma or any cellular atypia. Histopathology was suggestive of Odontogenic keratocyst (OKC) (Fig. 7).

Fig. 7.

Orthopantamograph of 6 months follow-up

Discussion

The Gorlin–Goltz syndrome is an autosomal dominant inherited syndrome manifested by multiple defects involving the skin, nervous system, eyes, endocrine system, and bones. It is also known as basal cell nevus syndrome, Gorlin syndrome, hereditary cutaneomandibular polyonocosis, multiple basal cell carcinoma syndrome, multiple nevoid basal cell epithelioma-jaw cysts, or bifid rib syndrome [7].

Evans et al. first established major and minor criteria for diagnosing this rare entity, which was later modified by Kimonis et al. According to them, diagnosis of GGS can be established when two major or one major and two minor features are present [4, 8].

Major Criteria

• Multiple BCC or one occurring under the age of 20 years.

• OKCs of the jaws.

• Palmar or plantar pits.

• Bilamellar calcification of the falx cerebri.

• Bifid, fused or markedly splayed ribs.

• First-degree relative with NBCCS.

Minor Criteria

• Macrocephaly.

• Congenital malformation: Cleft lip or palate, frontal bossing, coarse face, moderate or severe hypertelorism.

• Other skeletal abnormalities: Sprengel deformity, marked pectus deformity, polydactyly or syndactyly of the digits.

• Radiological abnormalities: Bridging of the sella turcica, vertebral anomalies such as hemivertebrae, fusion or elongation of the vertebral bodies, modeling defects of the hands and feet or flame-shaped hands or feet.

• Ovarian fibroma.

• Medulloblastoma.

Our patient had three major features, namely multiple OKCs in the jaw, calcification of the falx cerebri, bifid rib, and minor feature of having polydactyly, thus suggesting it to be a case of the GGS.

OKC now termed a “keratocystic odontogenic tumor” (KCOT) is a constant feature present in about 75% of cases with GGS. Which can be diagnosed with dental panoramic radiography. These may show a unilocular or multilocular pattern and the cystic spaces may have a smooth or scalloped border. Dental anomalies reported in GGS are Multiple odontogenic keratocysts (75–100%), maxillary hypoplasia, mandibular prognathism, high arched palate or prominent palatine ridges (40%), cleft lip/palate (4%), impacted teeth and/or agenesis (3%), ectopic teeth and malocclusion [9].

KCOT has a greater predilection for the mandible (69%) than the maxilla (31%) with the molar-ramus region being the most commonly affected site followed by the incisor-canine and premolar region [10]. In young patients, these cysts may be associated with unerupted teeth leading to tooth displacement and root resorption. They are asymptomatic unless secondarily infected and rarely cause pathological fractures [9].

Radiographically KCOT may occur as a unilocular or multilocular pattern and the cystic spaces may have smooth or scalloped borders. Multiple odontogenic keratocysts may be confirmatory of the syndrome [11]. Histologically, the syndromic KCOT shows a greater number of satellite cysts, solid islands of epithelial proliferation, intramural epithelial remnants, odontogenic rests within the capsule, increased para-keratinization and mitotic figures in the epithelium [12].

Surgical management of odontogenic keratocysts can be done by two approaches i.e., Conservative or aggressive. In the conservative method, simple enucleation with or without curettage and marsupialization is suggested. The Aggressive methods include peripheral ostectomy, chemical curettage with Carnoy’s solution and resection. Application of Carnoy’s solution into the cystic cavity for 3 min after enucleation results in a lower rate of recurrence (0–2.5%) without any damage to the inferior alveolar nerve [13]. Cryosurgery using liquid nitrogen is indicated in the large complex mandibular lesions approximating the vital structures [14]. The recurrence rate of KCOT after excision is reported to be ranging from 12% to 62.5% and multiple recurrences do occur. A recurring cyst can be a new cyst that originates from epithelial residue or a microcyst left behind in the overlying mucosa [15].

Conclusion

To summarize, it can be said that Gorlin–Goltz syndrome is a dominant autosomal genetic disorder, which is of particular interest to the oral and maxillofacial experts. The importance of recognition of this syndrome is because of its malignant potential. Our case highlights the importance of awareness of this rare syndrome, especially in young people without any skin lesions. The syndrome can be recognized by the presence of some major criteria. The OKC is the most common manifestation of this syndrome. Early diagnosis of the syndrome is important to reduce the associated complications, which are life-threatening and also require genetic counselling for the parents.

Author contributions

SV, SKK, and DN were involved in the diagnosis, radiographic imaging, dental treatment, and data collection. SV, VK, SKK, and DN were involved in the interpretation of the radiological findings. SV and VK were involved in drafting, editing, and revising the manuscript. All the authors read and approved the final version of the manuscript.

Declarations

Conflict of interest

The authors declare that they have no competing interests.

Informal Consent

Written informed consent was obtained from the patient for the publication of this case report.