| Abstract|| |
Gorlin Syndrome, a rare genodermatosis, otherwise known as Nevoid basal cell carcinoma syndrome (NBCCS) is a multisystem disease affecting skin, nervous system, eyes, endocrine glands, and bones. It is characterized by multiple basal cell carcinomas, palmoplantar pits, jaw cysts, and bony deformities like kyphoscoliosis and frontal bossing. We would like to report a case of Gorlin syndrome with classical features, as this is a rare genodermatosis.
Keywords: Basal cell carcinoma, Gorlin syndrome, Nevoid basal cell carcinoma syndrome, PTCH gene
|How to cite this article:|
Devi B, Behera B, Patro S, Pattnaik SS, Puhan MR. Gorlin syndrome. Indian J Dermatol 2013;58:241
What was known?
Gorlin syndrome is a rare genodermatosis with variable expressivity, associated with varied manifestations including multiple basal cell carcinomas and skeletal abnormalities
| Introduction|| |
The name 'Gorlin' is associated with many genodermatosis like 'Gorlin Sign' in Ehler Danlos syndrome, Goltz-Gorlin syndrome for focal dermal hypoplasia and Gorlin syndrome. Gorlin syndrome also known as Basal cell nevus syndrome (BCNS) or Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant genodermatosis characterized mainly by the presence of multiple basal cell carcinomas (BCCs), jaw cysts, and palmoplantar pits. ,, It was first described by Jarish and White in 1894 but its syndromic nature was not defined until 1960; defined by Gorlin and Goltz. We would like to report one classical case of Gorlin syndrome with varied manifestations.
| Case Report|| |
A 60-year-old man, of low socioeconomic status presented with complaints of mole like skin lesions in his face, back, and scalp since childhood. These lesions were insidious in onset and gradually increasing in size. On dermatological examination there were multiple, discrete, pigmented, well defined, nontender mobile plaques and nodules of varying sizes present over the face, around eyelids, forehead, and scalp, and few on back [Figure 1]. Most of the lesions had ulceration. Larger lesions were of size 3-4 cm over face having rolled out border and central ulceration covered with hemorrhagic crusts. His hairs, nails, and mucosa were normal. There was no family history of similar lesions.
On general examination the patient was of average built having Kyphoscoliosis, Macrocephaly, frontal bossing, broad depressed nasal bridge, high arched palate, [Figure 2] and hypertelorism. Ophthalmic examination was not contributory except left eye having divergent squint. Other systemic examinations were within normal limits. Routine investigations were within normal limits. Histopathology from one of the lesion was suggestive of BCC. Orthopantomogram (OPG) of the patient showed multiple jaw cysts present in maxilla. Skull X-ray and computed tomography (CT) scan brain showed calcification of Falx cerebri but magnetic resonance imaging (MRI) could not be done [Figure 3]. Chest X-ray showed bifid ribs. Ultrasonography of abdomen and pelvis were normal.
In the next visit, after 6 months, patient had new similar lesions and older lesions over back had increased in size and causing discomfort. Hence, different treatment modalities were approached. The larger lesions and few smaller lesions were excised, while rest lesions were treated with topical 5 fluorouracil (5-FU). Retinoid in high dose and prolonged duration is a good agent for treatment and prevention of BCC, but could not be tried, looking at his economic status.
| Discussion|| |
BCNS is an uncommon genodermatosis transmitted as an autosomal dominant trait exhibiting high penetrance and variable expressivity, mapped to chromosome 9q22.33.1.  Inherited or spontaneous mutations in the human homologue of Drosophila patched gene underlie the disorder. Due to variable expressivity all findings are not present in one patient. This disorder is known to run in families with an equal frequency in both sexes. Similar to the present case those who do not have any family members affected with BCNS may comprise 60% of total BCNS and 35-50% of these cases represent new mutations.
The skin manifestations of multiple BCCs in our case started in childhood and were around 8 to 10. This contrasts with classical presentation in which the tumors are innumerable and distributed in a bilaterally symmetrical manner. Other cutaneous manifestations of the syndrome include milia, epidermal and sebaceous cysts, lipomas, and fibromas. None of which were observed in our case.
Multiple odontogenic keratocysts arising from the rests of dental lamina of the mandible and occasionally the maxillae are common in this disorder with a peak incidence in the second and third decade of life. These are unilocular or multilocular lined by stratified squamous epithelium. These cysts may be complicated by the development of pathological fractures, amelobastomas, and squamous cell carcinomas and have a high rate of recurrence. Small cysts may be asymptomatic and can be detected only by radiologically as in our case. Pits on hands and feet are characteristic features of the syndrome. They have their onset during the second decade and become more frequent with advancing age. Our case showed these characteristics. It has been hypothesized that pits are a result of premature desquamation of most of the horny layer.
In the skull there is early onset of calcification of Falx cerebri, tentorium cerebri, dura, and choroids. Bridging of sella turcica due to calcification of the diaphragm sellae is seen in 60-80% of patients. Our patient had calcification of Falx cerebri. Neurological abnormalities include agenesis of the corpus callosum, congenital hydrocephalus, mental retardation, medulloblastomas, and meningiomas. Ophthalmological abnormalities seen are dystopia canthorum, internal strabismus, congenital blindness, and hypertelorism. Our patient had hypertelorism.
Other skeletal abnormalities include rib anomalies (splaying, synostosis, bifid, and cervical ribs), vertebral anomalies (block vertebra, hemivertebra, spina bifida occulta, and kyphoscoliosis), and shortening of the metacarpal and small flame lucency in phalanges.
Abnormalities of the reproductive system are ovarian and uterine fibromas in females and cryptorchidism and hypogonadism in males. Other findings in BCNS are mesenteric cysts, renal calculi, cardiac fibromas and a tendency to develop various other neoplastic lesions such as melanomas, neurofibromas, and rhabdomyosarcomas. Our patient had none of these findings.
The major diagnostic criteria include multiple BCCs, odontogenic keratocysts, palmar and plantar pits, flare calcification, and a positive family history. The minor criteria are congenital skeletal anomalies (ribs, vertebra), macrocrania, cardiac or ovarian fibromas, medulloblastomas, lymphomesenteric cysts, and congenital malformations (i.e., cleft lip/palate, polydactyly, eye anomalies). 
The presence of 2 major or 1 major or 2 minor criteria is diagnostic of Gorlin syndrome.  Our patient had four major (BCCs, Odontogenic cysts, palmoplantar pits, and falcine calcification) and one minor criteria (frontal bossing, kyphoscoliosis).
The importance of recognition of this syndrome is because of malignant potential. The fact that its transmission is autosomal dominant with good penetrance and any child of an affected family is at 50% risk of carrying the affected gene implies the need of genetic counseling. Regular follow up is necessary for assessing progression of BCCs.  In conclusion, we need to have a high index of suspicion to diagnose this rare syndrome as early diagnosis and genetic counseling could prevent consequences.
| References|| |
|1.||Gorlin RJ, Vickers RA, Kelln E, Williamson JJ. The multiple basal cell naevi syndromes: Analysis of a syndrome consisting of multiple naevoid basal cell carcinoma, jaw skeletal cyst, skeletal anomalies, medulloblastoma, hype responsiveness to parathormone. Cancer 1965;18:89-104. |
|2.||Gorlin RJ. The Naevoid basal cell carcinoma syndrome. Medicine (Baltimore) 1987;66:98-113. |
|3.||Fitzpatrick's Dermatology in General Medicine. 7 th ed. USA: McGraw-Hill Companies; 2008. p. 1042-3. |
|4.||Quinn AG. Molecular genetics of human non-melanoma skin cancer. Cancer Surv 1996;26:89-114. |
|5.||Kimonis VE, Goldstein AM, Pastakia B, Yang ML, Kase R, DiGiovanna JJ, et al. Clinical manifestations in 105 persons with naevoid basal cell carcinoma syndrome. Am J Med Genet 1997;69:299-308. |
|6.||Chavan RG, Phadke VA, Joshi R, Joshi KU , Wadhwa SL. Gorlin's syndrome. Indian J Dermatol 1998;43:175-8. |
What is new?
We are presenting a rare classical case of Gorlin syndrome with multiple
numbers of major and minor features
[Figure 1], [Figure 2], [Figure 3]