gorlin - goltz syndrome which is also known as nevoid basal cell carcinoma ( bcc ) syndrome is a rare autosomal dominant disorder with strong penetrance and extremely variable expressivity .
robert j. gorlin and robort w. goltz described the distinct syndrome , consisting of multiple nevoid bccs , jaw cysts , and bifid ribs .
it is characterized by multiple odontogenic keratocysts ( okc ) , multiple bccs , skeletal , dental , ophthalmic , and neurological abnormalities , intracranial ectopic calcifications of the falx cerebri and facial dysmorphism.[24 ] pathogenesis of the syndrome is attributed to abnormalities in the long arm of chromosome 9 ( q22.3-q31 ) and loss of , or mutations of human patched gene ( ptch1 gene ) .
diagnosis is based upon established major and minor clinical and radiological criteria and ideally confirmed by deoxyribo nucleic acid ( dna ) analysis . a case of gorlin - goltz syndrome
this syndrome is also named as gorlin syndrome , multiple nevoid basal cell epithelioma , jaw cyst bifid rib syndrome , or multiple nevoid bcc syndrome .
the frequency of the syndrome varies according to the country where the study has been carried out . on an average
, the incidence of gorlin - goltz syndrome has been reported to be 1 in 50,000 to 150,000 in general population .
the review of literature reveals that only seven cases of this syndrome are reported from india .
the syndrome manifests with some major and minor criteria like pigmented bccs , okc , palmar and/or plantar pits , and ectopic calcifications of the falx cerebri . to establish diagnosis , two major and one minor or one major and three minor criteria are necessary .
because of aggressive nature and high rate of recurrence , there should be periodic follow - up at regular intervals of 6 months till 5 years , followed by once annually for the entire life .
a 9-year - old girl presented to the department of oral medicine and radiology in vasantdada patil dental college and hospital , sangli , with complaint of swelling in the upper anterior region of right side of jaw since the last six months .
swelling had been increasing since the last 3 to 4 months and there was no pain associated with it .
intraoral examination revealed that the buccal sulcus on both sides was obliterated and there was expansion of the buccal cortical plates [ figures 1a  d ] .
clinical photographs ( a , b and c ) and intraoral photograph ( d ) of patient orthopantomogram ( opg ) was advised which revealed multiple round to oval radiolucencies which were suggestive of multiple cystic lesions [ figure 2 ] .
the erupting left and right second molar tooth also had a cyst - like radiolucency over the crown .
thus , seven cystic lesions ( three in maxilla and four in mandible ) were seen on opg . due to the presence of multiple cyst - like lesions in the jaws ,
opg showing multiple cystic lesions , three in maxilla and four in mandible an x - ray of the skull revealed calcification of falx cerebri [ figure 3 ] and a chest x - ray showed fused ribs [ figure 4 ] .
no skin lesion in the form of basal cell nevus , palmar or plantar pits , or keratosis were present .
ct scan brain showing calcification in falx cerebri chest x - ray showing fusion of 3rd and 4th ribs on left side all the cystic lesions of the jaw were enucleated surgically .
intraoperative photographs and photographs of excised tissue are shown in figures 5 and 6 , respectively .
the cystic lining was made up of uniformly thick , stratified squamous epithelium of 5 to 6 layers thick , flat with corrugated parakeratin surface .
underlying connective tissue capsule was loose fibrocellular , with supporting vasculature , extravasated blood elements , strands , and nests of odontogenic epithelium [ figures 7 a  c ] .
in all seven cysts , histopathologic features were suggestive of okc [ figure 7 ] .
ki 67 immunohistochemical staining was done which was positive ( 25% ) [ figure 8 ] .
intraoperative photographs photographs of excised tissue h and e stained photomicrographs of okc [ 10 ( a ) and 40 ( b and c ) ] in our patient , the diagnosis of gorlin - goltz syndrome was established by the presence of three major criteria ( multiple okc , bifid ribs , and calcifications of falx cerebri ) and one minor criterion ( figure 1c showing increased occipitofrontal circumference ) .
in order to make a diagnosis of the gorlin - goltz syndrome , some diagnostic criteria have to be taken into account . the most important criteria to make a diagnosis for this syndrome are the presence of pigmented basocellular carcinomas , okc , palmar and/or plantar pits , and ectopic calcifications of the falx cerebri.[811 ] together with these major features , more than 100 minor features have been described .
the more relevant are the following : cardiac or ovarian fibroma , macroencephaly , bifid ribs , kyphoscoliosis , cleft palate , medulloblastoma , alterations in the sella turcica , mandibular prognathia , lateral displacement of the inner canthus , frontal and biparietal bossing , imperfect segmentation of the cervical vertebrae , linfomesenteric cysts that tend to calcify , meningiomas , fibrosarcoma , rhabdomyosarcoma , short fourth metacarpal , ocular hypertelorism , congenital blindness , high arched eyebrows and palate , narrow sloping shoulders , immobile thumbs , low pitch voice in women , renal anomalies , and hypogonadism in men . in certain occasions , a tall height and even similar characteristics to acromegaly
first established major and minor criteria for the diagnosis of the syndrome and later were modified by kimonis et al . in 2004 .
the presence of two major and one minor or one major and three minor criteria are necessary to establish diagnosis . 

multiple basal cell carcinomas or one occurring under the age of 20 years.histologically proven okcs of the jaws.palmar or plantar pits ( three or more).bilamellar calcifications of the falx cerebri.bifid , fused , or markedly splayed ribs.first degree relative with nevoid basal cell carcinoma syndrome . 
 
macrocephaly ( adjusted for height).congenital malformation : cleft lip or cleft palate , frontal bossing , coarse face moderate or severe hypertelorism.other skeletal abnormalities : sprengel deformity , marked pectus deformity , marked syndactyly of the digits.radiological abnormalities : bulging of sella turcica , vertebral anomalies such as hemi vertebrae , fusion or elongation of vertebral bodies , modeling defects of the hands and feet , or flame - shaped hands or feet.ovarian fibroma.medulloblastoma . 
 
congenital malformation : cleft lip or cleft palate , frontal bossing , coarse face moderate or severe hypertelorism .
other skeletal abnormalities : sprengel deformity , marked pectus deformity , marked syndactyly of the digits .
radiological abnormalities : bulging of sella turcica , vertebral anomalies such as hemi vertebrae , fusion or elongation of vertebral bodies , modeling defects of the hands and feet , or flame - shaped hands or feet .
gorlin - goltz syndrome is an autosomal dominant disorder with a high penetrance and variable expressivity .
it is caused by mutations in the patched tumor suppressor gene ( ptch ) , a human homologue of the drosophila gene mapped to chromosome 9q21 - 23 .
chromosomal mapping and genetic studies suggest that the underlying basis for this disease is an abnormality in the hedgehog ( hh ) signaling pathway .
the ptch gene product is part of a receptor for the protein called sonic hedgehog , which is involved in embryonic development .
more recent investigations reveal the role of the hh pathway in cell cycle regulation in adults . in the drosophila model ,
the primary receptor for the hh signaling pathway has two transmembrane protein components : patched ( ptc ) and smoothened ( smo ) . in the absence of hh protein
hh , when present , binds ptc , releasing smo to affect downstream events such as cell growth and differentiation .
based on this model , inactivation of ptc or constitutive activity of smo or hh could lead to overactivity of smo , resulting in neoplasm formation .
woolgar et al . in 1987 concluded that mean age group for syndromic cases is 10 to 30 years and females are more affected than males .
okc associated with basal cell nevus syndrome showed more number of satellite cyst , solid islands of epithelial proliferation and odontogenic rests within the capsule , and increased mitotic figures in the epithelium lining the main cavity .
okc 's falling in the category of keratocystic odontogenic tumor ( kcot ) may be associated with gorlin - goltz syndrome in the form of multiple cystic lesions .
analyzed the neoplastic nature and biological potential of sporadic and nevoid basal cell carcinoma syndrome ( nbccs)-associated kcot .
heparanase is an endo - d - glucuronidase enzyme that specifically cleaves heparan sulfate and the increase of its level in tumors promotes invasion , angiogenesis , and metastasis . in his study , all odontogenic cysts have shown positive immunoreactions for the heparanase for the heparin protein in various intensities .
intense gene and protein expressions have been observed in kcot associated with nbccs , as compared with sporadic ones and dentigerous cyst .
so , heparanase expression may be correlated with the neoplastic properties of kcot , particularly in nbccs - associated cases .
apart from surgical enucleation for cystic lesions , adjunctive therapies like chemical cauterization is useful to prevent recurrence by fixing the daughter cyst or remnants of epithelial lining that are not removed during the enucleation procedure .
have demonstrated that carnoy 's solution penetrates the bone to the depth 1.54 mm following a 5 minutes application without any damage to the inferior alveolar nerve .

 multiple basal cell carcinomas or one occurring under the age of 20 years.histologically proven okcs of the jaws.palmar or plantar pits ( three or more).bilamellar calcifications of the falx cerebri.bifid , fused , or markedly splayed ribs.first degree relative with nevoid basal cell carcinoma syndrome . 
 
multiple basal cell carcinomas or one occurring under the age of 20 years . histologically proven okcs of the jaws .

 macrocephaly ( adjusted for height).congenital malformation : cleft lip or cleft palate , frontal bossing , coarse face moderate or severe hypertelorism.other skeletal abnormalities : sprengel deformity , marked pectus deformity , marked syndactyly of the digits.radiological abnormalities : bulging of sella turcica , vertebral anomalies such as hemi vertebrae , fusion or elongation of vertebral bodies , modeling defects of the hands and feet , or flame - shaped hands or feet.ovarian fibroma.medulloblastoma . 
 
congenital malformation : cleft lip or cleft palate , frontal bossing , coarse face moderate or severe hypertelorism .
other skeletal abnormalities : sprengel deformity , marked pectus deformity , marked syndactyly of the digits .
radiological abnormalities : bulging of sella turcica , vertebral anomalies such as hemi vertebrae , fusion or elongation of vertebral bodies , modeling defects of the hands and feet , or flame - shaped hands or feet .
gorlin - goltz syndrome is an autosomal dominant disorder with a high penetrance and variable expressivity .
it is caused by mutations in the patched tumor suppressor gene ( ptch ) , a human homologue of the drosophila gene mapped to chromosome 9q21 - 23 .
chromosomal mapping and genetic studies suggest that the underlying basis for this disease is an abnormality in the hedgehog ( hh ) signaling pathway .
the ptch gene product is part of a receptor for the protein called sonic hedgehog , which is involved in embryonic development .
more recent investigations reveal the role of the hh pathway in cell cycle regulation in adults . in the drosophila model ,
the primary receptor for the hh signaling pathway has two transmembrane protein components : patched ( ptc ) and smoothened ( smo ) . in the absence of hh protein
hh , when present , binds ptc , releasing smo to affect downstream events such as cell growth and differentiation .
based on this model , inactivation of ptc or constitutive activity of smo or hh could lead to overactivity of smo , resulting in neoplasm formation .
woolgar et al . in 1987 concluded that mean age group for syndromic cases is 10 to 30 years and females are more affected than males .
okc associated with basal cell nevus syndrome showed more number of satellite cyst , solid islands of epithelial proliferation and odontogenic rests within the capsule , and increased mitotic figures in the epithelium lining the main cavity .
okc 's falling in the category of keratocystic odontogenic tumor ( kcot ) may be associated with gorlin - goltz syndrome in the form of multiple cystic lesions .
analyzed the neoplastic nature and biological potential of sporadic and nevoid basal cell carcinoma syndrome ( nbccs)-associated kcot .
heparanase is an endo - d - glucuronidase enzyme that specifically cleaves heparan sulfate and the increase of its level in tumors promotes invasion , angiogenesis , and metastasis . in his study , all odontogenic cysts have shown positive immunoreactions for the heparanase for the heparin protein in various intensities .
intense gene and protein expressions have been observed in kcot associated with nbccs , as compared with sporadic ones and dentigerous cyst .
so , heparanase expression may be correlated with the neoplastic properties of kcot , particularly in nbccs - associated cases .
apart from surgical enucleation for cystic lesions , adjunctive therapies like chemical cauterization is useful to prevent recurrence by fixing the daughter cyst or remnants of epithelial lining that are not removed during the enucleation procedure .
have demonstrated that carnoy 's solution penetrates the bone to the depth 1.54 mm following a 5 minutes application without any damage to the inferior alveolar nerve .
not many cases have been reported in india , and hence we report here a rare case and importance of multidisciplinary approach in management of the syndrome .
thorough extraoral and intraoral examinations along with opg , skull and chest radiographs help in proper diagnosis of the condition .
this investigation prompts an early verification of the disease , which is very important to prevent recurrence and better survival rates from the existent diseases .
okc of the jaws which can cause disfigurement of the face , mobility and even loss of teeth can be avoided by early detection and treatment of the same .
 gorlin - goltz syndrome is an uncommon autosomal dominant inherited disorder , which is characterized by multiple odontogenic keratocysts and basal cell carcinomas , skeletal , dental , ophthalmic , and neurological abnormalities , intracranial ectopic calcifications of the falx cerebri , and facial dysmorphism . 
 pathogenesis of the syndrome is attributed to abnormalities in the long arm of chromosome 9 ( q22.3-q31 ) and loss or mutations of human patched gene ( ptch1 gene ) . 
 diagnosis is based upon established major and minor clinical and radiological criteria and ideally confirmed by deoxyribo nucleic acid analysis . 
 we report a case of a 9-year - old girl presenting with three major and one minor feature of gorlin - goltz syndrome . 
 radiologic findings of the syndrome are easily identifiable on orthopantomogram , chest x - ray , and computed tomography scans . 
 these investigations prompt an early verification of the disease , which is very important to prevent recurrence and better survival rates from the coexistent diseases . 
INTRODUCTION
CASE REPORT
DISCUSSION
Major criteria
Minor criteria
CONCLUSION