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J Indian Soc Pedod Prev Dent- December 2005 198

Gorlin syndrome: A case report


PATIL K.
a
, MAHIMA V. G.
b
, GUPTA B.
c
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.
Key words: Basal cell carcinoma, Gorlin syndrome, Nevoid basal cell carcinoma, Odontogenic keratocysts, Palmar/Plantar
pits
ISSN 0970 - 4388
a
Professor & Head of the Department,
b
Professor,
c
Postgraduate,
Department of Oral Medicine and Radiology, JSS Dental College
and Hospital, Mysore-15
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 con-
sistency 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 dis-
tally unto 26. Mucosa over the swelling showed no second-
ary changes [Figure 4]. On palpation the swelling was ten-
der and soft in consistency with areas of decortication. As-
piration yielded thin straw-coloured fluid.
Based on the history and clinical findings, a provisional di-
agnosis of dentigerous cyst in relation to 63 was given and
a differential diagnosis of odontogenic keratocyst
considered.The patients was subjected to the following ra-
diographic examination.
Intraoral periapical radiograph in the region of 22,63 and
26 showed a well-defined radiolucency with sclerotic bor-
ders 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]. Ante-
rior maxillary occlusal radiograph showed similar well-de-
fined radiolucency in the region of 22,63,26 [Figure 6].
Orthopantomograph revealed multiple, unilocular well de-
fined radiolucencies with sclerotic borders located in max-
illa 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
Basal cell nevus syndrome or Gorlin syndrome was first re-
ported by Jarisch and White in 1894.
[1]
The incidence of this
syndrome is estimated to be 1 in 50,000 to 150,000 in gen-
eral population, but perceived incidence may vary by re-
gion.
[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 domi-
nant 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 anoma-
lies. A spectrum of other neurological, ophthalmic, endo-
crine and genital manifestations are known to be variably
associated with this triad.
[2]
Case Report
A female patient aged 13 years of age visited the Depart-
ment 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.
Patients medical, family, dental and personal history were
noncontributory.
On general physical examination, the patient was moder-
ately 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].
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J Indian Soc Pedod Prev Dent- December 2005 199
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 radiolu-
Figure 1: Multiple palmar pits on the hand
Figure 2: Extraoral photograph showing frontal bossing and
profile view showing diffuse swelling of left middle third of the
face
Figure 3: Intraoral photograph of maxillary arch
Figure 4: Swelling in left buccal vestibule causing obliteration
Figure 5: Intraoral periapical radiograph in relation to 22 upto
26
Figure 6: Anterior maxillary occlusal view
cency in the periapical region of 36 extending upto middle
third of anterior one third of ramus of the mandible displac-
ing the tooth bud of 38 distally.
Gorlin syndrome
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J Indian Soc Pedod Prev Dent- December 2005 200
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 calcifica-
tion of the falx cerebri [Figure 8]. Chest radiograph [Figure
9], hand wrist radiograph, anteroposterior view of dorsolat-
eral side of the spine was also taken and no osseous anoma-
lies were observed. The patient was then evaluated systemi-
cally 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 re-
vealed bitot spots in both the eyes. An incisional biopsy of
the swelling in left side of maxilla was advised. Histopatho-
logical examination of specimen revealed stratified squa-
mous parakeratinised epithelium with palisading pattern of
Figure 9: Chest radiograph
Figure 10: Histological section showing stratified squamous
parakeratinised epithelium with palisading pattern of columnar
cells along with keratin flakes suggestive of odontogenic
keratocyst under low power (10 X)
Figure 11: Histological section showing stratified squamous
parakeratinised epithelium with palisading pattern of columnar
cells along with keratin flakes suggestive of odontogenic
keratocyst under high power (40 X)
Figure 7: Orthopantomograph showing multiple jaw cysts in
relation to impacted and unerupted teeth
Figure 8: Posteroanterior view of the skull showing falx cerebri
calcification
Gorlin syndrome
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J Indian Soc Pedod Prev Dent- December 2005 201
columnar cells along with keratin flakes suggestive of odon-
togenic keratocyst [Figure 10 & 11].
Since the criteria of multiple cysts in the jaws (one of them
being odontogenic keratocyst), multiple palmar pits, fron-
tal bossing and falx cerebri calcification were present; a fi-
nal diagnosis of Gorlin syndrome was given. Patient was re-
ferred 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 condi-
tion that exhibits high penetrance and variable expressivity,
caused by mutations in patched tumor suppressor gene
(PTCH), a human homologue of Drosophila segment polar-
ity gene mapped to chromosome 9q22.3 q 31.
[3,4]
The syndrome is synonymous with Nevoid basal cell carci-
noma, 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 mul-
tiple neoplasms including basal cell carcinomas and medullo-
blastomas.
[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 syn-
drome can be established when two major or one major
and two minor criteria as described below are present.
MAJOR CRITERIA
[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
[2,6]
- Congenital skeletal anomaly, bifid, fused, splayed, miss-
ing 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, mi-
crophthalmus).
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 af-
fected
2. Scoliosis - seen in 30- 40% of the patients
3. Hemivertebrae
4. Flame Shaped lucencies of hand/ feet
5. Polydactyly
6. Syndactyly
7. Shortened 4
th
metacarpal
B. Craniofacial anomalies
[2,7]
1. Frontal bossing (25%)- Increased size of calvaria (occipi-
tofrontal 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 in-
fancy
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
Gorlin syndrome
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J Indian Soc Pedod Prev Dent- December 2005 202
patients.
[3]
They develop during the first decade of life,
usually after the 7
th
year and reach the peak during 2
nd
and 3
rd
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 re-
gion.
[8,9]
Their high mitotic index suggests greater pro-
liferative potential of the epithelial lining for cyst ex-
pansion 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 de-
veloping teeth and may be associated with unerupted teeth
and occasionally cause root resorption. In spite of wide-
spread extension throughout the jaws, they are asymptom-
atic, unless secondarily infected. They are detected on rou-
tine 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 is-
lands 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 Carnoys
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 syn-
drome.
[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
3
rd
decade of life.
[7]
After puberty they can become ag-
gressive and locally invasive.
[2,7]
Tumor may vary from
flesh coloured papules to ulcerating plaques. They of-
ten 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 in-
volvement 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 curet-
tage.
[2]
Photodynamic therapy by use of photosensitiz-
ing 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 patients
hands or feet are placed in warm water for several min-
utes. Basal cell carcinomas may arise from these pits
[7]
.
Multiple palmar pits became evident when we placed
our patients 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 diag-
nosis 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 syn-
drome causes death during infancy.
[7]
Because of recurrence
of odontogenic keratocysts, varying degree of jaw defor-
mity may result from operations for multiple cysts.
[3]
Gorlin syndrome
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J Indian Soc Pedod Prev Dent- December 2005 203
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 his-
tologically 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 exami-
nation 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 examina-
tion 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
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, Depart-
ment of Oral Pathology, JSS Dental College and Hospital,
Mysore.
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Reprint requests to:
Dr. Karthikeya Patil,
Professor & Head of the Department,
Department of Oral Medicine and Radiology,
JSS Dental College and Hospital, Mysore-15
Gorlin syndrome
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