Gorlin syndrome

Alternative Names:Nevoid basal cell carcinoma syndrome (NBCCS),basal cell nevus syndrome, multiple basal cell carcinoma syndrome and Gorlin–Goltz syndrome

Definition:
Gorlin syndrome is an inherited medical condition involving defects within multiple body systems such as the skin, nervous system, eyes, endocrine system, and bones. People with this syndrome are particularly prone to developing a common and usually non-life-threatening form of non-melanoma skin cancers.


You may click to see more pictures of  Gorlin syndrome

People with the syndrome have a predisposition to multiple basal cell carcinomas (a form of skin cancer), jaw cysts and other generally harmless abnormalities in the bone. The severity of the disease can be wide-ranging.

About 10% of people with the condition do not develop basal cell carcinomas (BCCs). the name Gorlin syndrome refers to researcher Robert J. Gorlin (1923–2006).

First described in 1960, NBCCS is an autosomal dominant condition that can cause unusual facial appearances and a predisposition for basal cell carcinoma, a malignant type of skin cancer. The prevalence is reported to be 1 case per 56,000-164,000 population. Recent work in molecular genetics has shown NBCCS to be caused by mutations in the PTCH (Patched) gene found on chromosome arm 9q. If a child inherits the defective gene from either parent, he or she will have the disorder

Incidence:
About 750,000 new cases of sporadic basal cell carcinomas (BCCs) occur each year in the United States. Ultraviolet (UV) radiation from the sun is the main trigger of these cancers, and people with fair skin are especially at risk. Most sporadic BCCs arise in small numbers on sun-exposed skin of people over age 50, although younger people may also be affected. By comparison, NBCCS has an incidence of 1 in 50,000 to 150,000 with higher incidence in Australia. One aspect of NBCCS is that basal cell carcinomas will occur on areas of the body which are not generally exposed to sunlight, such as the palms and soles of the feet and lesions may develop at the base of palmer and plantar pits. One of the prime features of NBCCS is development of multiple BCCs at an early age, often in the teen years. Each person who has this syndrome is affected to a different degree, some having many more characteristics of the condition than others.

Components:-
Some or all of the following may be seen in someone with Gorlin Syndrome:

1.Multiple basal cell carcinomas of the skin
2.Odontogenic keratocyst: Seen in 75% of patients and is the most common finding. There are usually multiple lesions found in the mandible. They occur at a young age (19 yrs average).
3.Rib and vertebrae anomalies
4.Intracranial calcification
5.Skeletal abnormalities: bifid ribs, kyphoscoliosis, early calcification of falx cerebri (diagnosed with AP radiograph)
6.Distinct faces: frontal and temporopariental bossing, hypertelorism, and mandibular prognathism

What genes are related to Gorlin syndrome?
Mutations in the PTCH1 gene cause Gorlin syndrome. This gene provides instructions for making a protein called Patched-1, which functions as a receptor. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. Together, ligands and their receptors trigger signals that affect cell development and function. A protein called Sonic Hedgehog is the ligand for the Patched-1 receptor. Patched-1 prevents cell growth and division (proliferation) until Sonic Hedgehog is attached.

The PTCH1 gene is a tumor suppressor gene, which means it keeps cells from proliferating too rapidly or in an uncontrolled way. Mutations in this gene prevent the production of Patched-1 or lead to the production of an abnormal version of the receptor. An altered or missing Patched-1 receptor cannot effectively suppress cell growth and division. As a result, cells proliferate uncontrollably to form the tumors that are characteristic of Gorlin syndrome.

You may click to learn more about the PTCH1 gene.

How do people inherit Gorlin syndrome?
Gorlin syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the features that are present from birth, such as large head size and skeletal abnormalities. An affected person often inherits a PTCH1 mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family. For tumors to develop, a mutation in the other copy of the PTCH1 gene must occur in certain cells during the person’s lifetime. Most people who are born with one PTCH1 mutation eventually acquire a second mutation in certain cells and develop basal cell carcinomas and other tumors.

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Causes:-
Gorlin syndrome is an autosomal dominant condition. The abnormal gene is found on chromosome 9. New mutations (where neither parent carries the gene) are common.

Diagnosis:
Diagnosis of NBCCS is made by having 2 major criteria or 1 major and 2 minor criteria.

The major criteria consist of the following:

1.more than 2 BCCs or 1 BCC in a person younger than 20 years;
2.odontogenic keratocysts of the jaw
3.3 or more palmar or plantar pits
4.ectopic calcification or early (<20 years) calcification of the falx cerebri
5.bifid, fused, or splayed ribs
6.first-degree relative with NBCCS.

.
The minor criteria include the following:

1.macrocephaly.
2.congenital malformations, such as cleft lip or palate, frontal bossing, eye anomaly (cataract, colobma, microphtalmia, nystagmus).
3.other skeletal abnormalities, such as Sprengel deformity, pectus deformity, polydactyly, syndactyly or hypertelorism.
4.radiologic abnormalities, such as bridging of the sella turcica, vertebral anomalies, modeling defects or flame-shaped lucencies of hands and feet.
5.ovarian and cardio fibroma or medulloblastoma (the latter is generally found in children below the age of two).
People with NBCCS need education about the syndrome, and may need counseling and support, as coping with the multiple BCCs and multiple surgeries is often difficult. They should reduce UV light exposure, to minimize the risk of BCCs. They should also be advised that receiving Radiation therapy for their skin cancers may be contraindicated. They should look for symptoms referable to other potentially involved systems: the CNS, the genitourinary system, the cardiovascular system, and dentition.

Genetic counseling is advised for prospective parents, since one parent with NBCCS causes a 50% chance that their child will also be affected.

Treatment:
Although there’s no cure, the carcinomas can be treated by surgery, lasers or photodynamic therapy, which reduces scarring.

If there’s a family history of the syndrome, it’s possible for family members to be tested to see if they carry the faulty gene.

Those with Gorlin syndrome are now advised to avoid – or to take advice before undergoing – any radiation treatment, as it’s thought it may exacerbate the condition.

Treatment is usually supportive treatment, that is, treatment to reduce any symptoms rather than to cure the condition.

*Enucleation of the odontogenic cysts can help but new lesions, infections and jaw deformity are usually a result.
*The severity of the basal cell carcinoma determines the prognosis for most patients. BCCs rarely cause gross disfigurement, disability or death .

*Genetic counseling

Advice and support:-
•Gorlin Syndrome Group
•Tel: 01772 496849
•Email: info@gorlingroup.org
•Website: www.gorlingroup.org

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:
http://www.bbc.co.uk/health/physical_health/conditions/gorlinsyndrome1.shtml
http://en.wikipedia.org/wiki/Nevoid_basal_cell_carcinoma_syndrome
http://ghr.nlm.nih.gov/condition/gorlin-syndrome
http://dermnetnz.org/systemic/gorlins.html

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