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CASE REPORTS
Year : 2005  |  Volume : 23  |  Issue : 4  |  Page : 198-203
 

Gorlin syndrome: A case report


Department of Oral Medicine and Radiology, JSS Dental College and Hospital, Mysore-15, India

Correspondence Address:
K Patil
Professor & Head of the Department,Department of Oral Medicine and Radiology,JSS Dental College and Hospital, Mysore-15
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-4388.19010

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   Abstract 

Gorlin syndrome is an autosomal dominant inherited condition that exhibits high penetrance and variable expressivity. It is characterized mainly by Basal cell carcinomas, Odontogenic keratocysts and skeletal anomalies. However, medical literature documents both common and lesser known manifestations of the disorder involving the skin, central nervous system, skeletal system etc. Diagnosis of the syndrome in childhood is basically through oral abnormalities. A case of Gorlin syndrome has been reported here, with review of literature.


Keywords: Basal cell carcinoma, Gorlin syndrome, Nevoid basal cell carcinoma, Odontogenic keratocysts, Palmar/Plantar pits


How to cite this article:
Patil K, Mahima V G, Gupta B. Gorlin syndrome: A case report. J Indian Soc Pedod Prev Dent 2005;23:198-203

How to cite this URL:
Patil K, Mahima V G, Gupta B. Gorlin syndrome: A case report. J Indian Soc Pedod Prev Dent [serial online] 2005 [cited 2019 Dec 16];23:198-203. Available from: http://www.jisppd.com/text.asp?2005/23/4/198/19010


Basal cell nevus syndrome or Gorlin syndrome was first reported by Jarisch and White in 1894.[1] The incidence of this syndrome is estimated to be 1 in 50,000 to 150,000 in general population, but perceived incidence may vary by region.[1] It arises in all ethnic groups, but most reports have been in whites. Males and females are equally affected. The clinical features of nevoid basal cell carcinoma arise in the first, second or third decade of life as an autosomal dominant mode of inheritance but, can arise spontaneously or can have a variable phenotypic penetration.[2] Gorlin and Goltz defined the condition as a syndrome comprising the triad of basal cell nevi, jaw keratocysts and skeletal anomalies. A spectrum of other neurological, ophthalmic, endocrine and genital manifestations are known to be variably associated with this triad.[2]


   Case Report Top


A female patient aged 13 years of age visited the Department of Oral Medicine and Radiology, JSS Dental College and Hospital, Mysore with a chief complaint of swelling on the left side of the upper jaw since 5 months. She gave a history of slowly progressing swelling initially the size of a peanut which had gradually increased to attain the present size. Patient was concerned about the facial deformity and denied any other associated symptoms.

Patient's medical, family, dental and personal history were noncontributory.

On general physical examination, the patient was moderately built and nourished, presenting with normal gait and satisfactory vital signs There were multiple palmar pits each measuring 0.2-0.3mm in diameter and brownish black in color present on the palms of both her hands [Figure - 1]. Webbing was noticed between middle and ring fingers of both her hands. Examination of the face showed frontal bossing There was a diffuse swelling in the left middle third of the face with no secondary changes noted over it [Figure - 2]. On palpation, there was local rise in temperature; the swelling was tender and soft in consistency. A solitary left submandibular lymph node was palpable, tender, soft in consistency and mobile.

Intraorally, permanent complement of teeth were present except 23,24,25, which were clinically missing [Figure - 3].

There was a swelling in the left buccal vestibule causing vestibular obliteration in region of 22 and 63 extending distally unto 26. Mucosa over the swelling showed no secondary changes [Figure - 4]. On palpation the swelling was tender and soft in consistency with areas of decortication. Aspiration yielded thin straw-coloured fluid.

Based on the history and clinical findings, a provisional diagnosis of dentigerous cyst in relation to 63 was given and a differential diagnosis of odontogenic keratocyst considered.The patients was subjected to the following radiographic examination.

Intraoral periapical radiograph in the region of 22,63 and 26 showed a well-defined radiolucency with sclerotic borders in the periapical region extending from 22 to 26. The radiolucency was not associated with impacted teeth. The radiograph also showed missing 23,24,25 [Figure - 5]. Anterior maxillary occlusal radiograph showed similar well-defined radiolucency in the region of 22,63,26 [Figure - 6].

Orthopantomograph revealed multiple, unilocular well defined radiolucencies with sclerotic borders located in maxilla and mandible as described below [Figure - 7].

Well defined radiolucency extending from periapical region of 21 to 26, an enlarged follicular space in relation to 18 and displacing the tooth into the sinus and a radiolucency in the periapical region of 47 extending to anterior one third of ramus of the mandible was seen. Interdentally, there were radiolucencies in the periapical region of 32, 33 and 43, 44, 45 displacing the roots of the same laterally and radiolucency in the periapical region of 36 extending upto middle third of anterior one third of ramus of the mandible displacing the tooth bud of 38 distally.

The presence of multiple cysts in the jaws, associated with unerupted teeth, raised a suspicion of Gorlin Syndrome and other relevant investigations were done.

Anteroposterior view of the skull showed linear calcification of the falx cerebri [Figure - 8]. Chest radiograph [Figure - 9], hand wrist radiograph, anteroposterior view of dorsolateral side of the spine was also taken and no osseous anomalies were observed. The patient was then evaluated systemically for other anomalies of the skeletal, cardiovascular or central nervous system.

Pediatric examination revealed increased head circumference to 56 cms.(normal head circumference is 54 cms for a 13-year-old girl) Ophthalmologic examination incidentally revealed bitot spots in both the eyes. An incisional biopsy of the swelling in left side of maxilla was advised. Histopathological examination of specimen revealed stratified squamous parakeratinised epithelium with palisading pattern of columnar cells along with keratin flakes suggestive of odontogenic keratocyst [Figure - 10][Figure - 11].

Since the criteria of multiple cysts in the jaws (one of them being odontogenic keratocyst), multiple palmar pits, frontal bossing and falx cerebri calcification were present; a final diagnosis of Gorlin syndrome was given. Patient was referred to the Department of Oral and Maxillofacial Surgery where enucleation of all cysts was done. Patient is being followed up regularly.

Gorlin syndrome is an autosomal dominant inherited condition that exhibits high penetrance and variable expressivity, caused by mutations in patched tumor suppressor gene (PTCH), a human homologue of Drosophila segment polarity gene mapped to chromosome 9q22.3 - q 31.[3],[4]

The syndrome is synonymous with Nevoid basal cell carcinoma, Jaw cyst bifid rib basal cell nevus syndrome, Nevoid basalioma and Gorlin Goltz syndrome.[5]

The syndrome was reported by Jarisch and White in 1794 and later in detail by Gorlin in 1960.[2],[5]

Familiarity with Gorlin syndrome is important for clinicians because of the propensity of these patients to develop multiple neoplasms including basal cell carcinomas and medulloblastomas.[1]

The diagnostic criteria for nevoid basal cell carcinoma was put forth by Evans and colleague and modified by Kimonis et al. in 1997. According to him, diagnosis of Gorlin syndrome can be established when two major or one major and two minor criteria as described below are present.


   Major criteria Top
[2],[6]

-More than two basal cell carcinoma or one basal cell carcinoma at younger than thirty years of age or more than ten basal cell nevi.

-Any odontogenic keratocyst (proven on histology) or polyostotic bone cyst.

-Three or more palmar or plantar pits.

-Ectopic calcification: Lamellar or early at younger than twenty years of age

-Falx cerebri calcification.

-Positive family history of nevoid basal cell carcinoma.


   Minor criteria Top
[2],[6]

-Congenital skeletal anomaly, bifid, fused, splayed, missing or bifid rib, wedged or fused vertebra.

-Occipital - frontal circumference more than 97%.

-Cardiac or ovarian fibroma.

-Medulloblastoma.

-Lymphomesentric cysts.

-Congenital malformations such as cleft lip or palate, polydactylism or eye anomaly (cataract, coloboma, microphthalmus).

In our case three major (Palmar pits, odontogenic keratocyst proven histologically and falx cerebri calcification) and one minor (increased occipitofrontal circumference) criteria were met which were indicative of Gorlin syndrome.

Other diagnostic findings in adults with Nevoid basal cell carcinoma reported by Gorlin and his colleagues [7] and their incidence of occurrences are:

A.Skeletal anomalies [2],[7]

1.Bifid ribs, splayed/ fused ribs, absent/ rudimentary ribs (60-75%)- may be bilateral and several ribs may be affected

2.Scoliosis - seen in 30- 40% of the patients

3.Hemivertebrae

4.Flame - Shaped lucencies of hand/ feet

5.Polydactyly

6.Syndactyly

7.Shortened 4th metacarpal

B.Craniofacial anomalies [2],[7]

1.Frontal bossing (25%)- Increased size of calvaria (occipitofrontal circumference 60 cms. or > in adults

2.Brachycephaly

3.Macrocephaly (40%)

4.Coarse face (50%)

5.Calcification of the falxes (37-79%)

6.Tentorium cerebelli calcification

7.Bridged sella tursica

8.Heavy fused eyebrows

9.Broadened nasal root

10.Low positioning of occiput

11.Congenital blindness due to corneal opacity

12.Congenital or precocious cataract or glaucoma

13.Coloboma of iris, choroids or optic nerve

14.Convergent or divergent strabismus and nystagmus

C.Neurological anomalies[2],[7]

1.Agenesis / disgenesis of corpus callosum

2.Congenital hydrocephalus

3.Mental retardation

4.Medulloblastoma (3-5%) - developing in the first two years of life. About 20% of them cause death during infancy

5.Meningioma (1% or <)

6.Schizoid personality

D.Oropharyngeal anomalies [2],[7] - Oral abnormalities are of fundamental importance mainly in childhood and adolescence and are important signs for diagnosis. They are

1.Cleft lip/ palate (4%)

2.High arched palate or prominent ridges (40%)

a.Odontogenic Keratocysts - These are constant features of this syndrome and are present in about 75% of the patients.[3] They develop during the first decade of life, usually after the 7th year and reach the peak during 2nd and 3rd decade. This approximately is a decade earlier than the much more common isolated odontogenic keratocyst not associated with the syndrome.[7] It is most commonly seen in the mandibular - molar- ramus region.[8],[9] Their high mitotic index suggests greater proliferative potential of the epithelial lining for cyst expansion due to proliferating cell nuclear antigen (PCNA) and its recurrence.[10],[11] Single or multiple, unilocular/ multilocular cysts have been demonstrated occurring in this syndrome.[7]

In young patients, the cysts can cause displacement of developing teeth and may be associated with unerupted teeth and occasionally cause root resorption. In spite of widespread extension throughout the jaws, they are asymptomatic, unless secondarily infected. They are detected on routine dental checkups and rarely cause pathological fractures. Although rare, ameloblastoma and squamous cell carcinoma have arisen form these cysts.[7]

Woolgar JA. et al. found significant differences histologically. Odontogenic keratocysts associated with Basal cell nevus syndrome showed more number of satellite cysts, solid islands of epithelial proliferation and odontogenic rests within the capsule and increased mitotic figures in the epithelium lining the main cavity.[12] Computed Tomography has been employed in estimating the size of the cysts.[5],[7]

Small cysts can be enucleated.[13] Larger cysts can be marsupialised.[14] Because of aggressiveness nature and high rate of recurrence, a sole surgical approach is unlikely to be successful, adjunctive therapies like cryosurgery or Carnoy's solution, decompression followed by secondary enucleation can also be done.[2]

Long term follow-up is advocated.

4.Malocclusions

5.Dental ectopic position

6.Impacted teeth and / or agenesis

Our patient showed multiple impacted teeth in the maxilla and mandible, one of them in the left side of the maxilla being associated with unilocular radiolucency, which was histologically proven as odontogenic keratocyst.

E.Skin anomalies

1.Basal cell carcinoma - These are major dermatological components seen in 50-97% of the people with the syndrome.[3] Suspicion for Gorlin Syndrome should be high if basal cell carcinomas are detected in pediatric age range. Basal cell carcinomas are also seen at puberty or 3rd decade of life.[7] After puberty they can become aggressive and locally invasive.[2],[7] Tumor may vary from flesh coloured papules to ulcerating plaques. They often appear on sun exposed skin. The area around the eyes, the nose, cheek bones and the upper lip are the most frequently affected sites on the face. Rarely wrist or extremities are involved. They may vary in number from a few hundreds to thousands and range in size from 1- 10 mm in diameter.[2],[3],[7] Blacks with this syndrome tend to have fewer basal cell carcinomas than whites because of protective skin pigmentation.[2],[3] That could explain why basal cell carcinoma was not seen in our patient. Ulcerating plaques can be mistaken for skin tags, nevi or hemangiomas.

Superficial basal cell carcinomas without hair follicle involvement are treated by topical use of 0.1% tretinoin cream and 5% fluorouracil applied to affected area twice daily.[1],[6],[7] The use of oral retinoids (isotretinoin - 3.1 mg/kg/day) or combined oral etretinate (0.5- 1 mg/kg/ day) is also suggested. Superficial basal cell carcinomas have also been managed by electrodessication and curettage.[2] Photodynamic therapy by use of photosensitizing dye given intravenously or topically has also been advocated. Radiation therapy must be avoided, as it can cause invasion of basal cell carcinoma years later.[6]

2.Palmar and/or plantar pits are present in about 65% of the patients. They are asymmetrical, ranging from 2-3 mm in diameter & 1-3 mm in depth. These pits usually develop late in the second decade but could be seen in patients as young as 5 years of age. They are caused by partial or complete absence of dense keratin in sharply defined areas. They become more evident when patient's hands or feet are placed in warm water for several minutes. Basal cell carcinomas may arise from these pits [7]. Multiple palmar pits became evident when we placed our patient's hands in warm water.[1],[3],[7]

F.Anomalies of the Reproductive system [2],[7]

1.Uterine and ovarian fibromas (15%)

2.Calcified ovarian cysts

3.Supernumerary nipple

4.Hypogonadism and cryptorchidism

G.Cardiac anomalies [2],[7]

1.Cardiac fibromas (3%)

The occurrence of findings associated with the syndrome varies from person to person and is important in diagnosis and formulating a treatment plan.

Complications

Aggressive basal cell carcinomas have caused death of the patient as a result of tumor invasion to the brain or other vital structures.[3] Medulloblastoma associated with the syndrome causes death during infancy.[7] Because of recurrence of odontogenic keratocysts, varying degree of jaw deformity may result from operations for multiple cysts.[3]

Odontogenic keratocysts are often the first signs of nevoid basal cell carcinoma and can be detected in patients younger than 10 years of age. An odontogenic keratocyst proven histologically in a child or onset of basal cell carcinoma in a patient younger than 20 years of age should alert the oral diagnostician to the possibility of the patient having nevoid basal cell carcinoma. A complete intra and extraoral examination should be done along with appropriate radiographic investigations. Panoramic radiograph once a year from age 7 years onwards is suggested along with dermatological examinations annually to identify the syndrome early and to detect anomalies in jaws and skin. Prenatal ultrasound to detect CNS, skeletal abnormalities, neurological examination every 6 months until 7 years of age is a must. Carrying out genetic analysis is advised to identify carriers.

Early diagnosis and treatment is important to prevent long term sequelae including malignancy and oromaxillofacial deformation and destruction.


   Acknowledgement Top


The authors thank Dr. Chandramohan, Professor and Head of Department of Oral and Maxillofacial Surgery, Dr. Saikrishna, Professor, Department of Oral and Maxillofacial Surgery and Dr. Sudheendra, Associate Professor, Department of Oral Pathology, JSS Dental College and Hospital, Mysore.

 
   References Top

1.Deepa MS, Paul R, Balan A. Gorlin Goltz Syndrome. A review. Journal of Indian Association of Oral Medicine and Radiology 2003;15:203-9.  Back to cited text no. 1    
2.Manfredi M, Vescovi P, Bonanini M, Porter S. Nevoid Basal Cell Carcinoma Syndrome A review of literature. Int J Oral Maxillofac Surg 2004;33:117-24.  Back to cited text no. 2    
3. In : Neville BW, Damm DD, Allen CM, Bouquot JE, editors. Oral and Maxillofacial Pathology. 2nd edn. New Delhi: Elsevier; 2002. p. 598-601.  Back to cited text no. 3    
4.Cohen MM. Nevoid Basal Cell Carcinoma- A molecular biology and new hypothesis. Int J Oral Maxillofac Surg 1996;27:216-23.  Back to cited text no. 4    
5.Mamatha GP, Reddy S, Rao B, Mujib A. Gorlin Syndrome. A case report. Indian J Dent Res 2001;12:247-52.  Back to cited text no. 5    
6.Muzio LL, Nocini P, Bucci P, Pannone G, Procaccini M. Early diagnosis of Nevoid Basal Cell Carcinoma Syndrome. J Am Dent Assoc 1999;130:669-74.  Back to cited text no. 6    
7.Gorlin RJ. Nevoid Basal Cell Carcinoma Syndrome. Medicine. Baltimore: Williams and Wilkins Co 1977;66:97-113.  Back to cited text no. 7    
8.Maroto MR, Porras JLB, Saez RS, Rios MH, Gozalez LB. The role of orthodontist in diagnosis of Gorlin Syndrome. Am J Ortho Dentofac Orthoped 1999;115:79-97.  Back to cited text no. 8    
9.Woolgar JA, Rippin JW, Browne RM. The Odontogenic Keratocyst and its occurrence in Nevoid Basal Cell Carcinoma Syndrome. Oral Surg Oral Med Oral Path 1977;64:727-30.  Back to cited text no. 9    
10.Woolgar JA, Rippin JW, Browne RM. A comparitive study of the clinical and histological features of recurrent and non recurrent odontogenic keratocyst. J Oral Path 1977;16:124-7.  Back to cited text no. 10    
11.Murtadi AEL, Grehan D, Toner M, McCartan BE. Proliferating cell nuclear antigen staining in syndrome and non syndrome odontogenic keratocyst. Oral Surg Oral Med Oral Path 1976;63:217-20.  Back to cited text no. 11    
12.Muzio L, Staibano S, Pannone G. Expression of cell cycle and apoptosis related proteins in sporadic odontogenic keratocyst and odontogenic keratocyst associated with Nevoid Basal Cell Carcinoma Syndrome. J Dent Res1999;77:1345-53.  Back to cited text no. 12    
13.Woolgar JA, Rippin JW, Browne RM. A comparitive histological study of odontogenic keratocysts in basal cell nevus syndrome. J Oral Path 1977;16:70-5.  Back to cited text no. 13    
14.Stoelinga PJW, Peters JH, Van de Staak WJB, Cohen MM. Some new findings in basal cell nevus syndrome. Oral Surg Oral Med Oral Path 1973;36:676-92.  Back to cited text no. 14    


Figures

[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7], [Figure - 8], [Figure - 9], [Figure - 10], [Figure - 11]


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    Abstract
    Case Report
    Major criteria
    Minor criteria
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