Gorlin-Goltz syndrome is a very rare genetic condition characterized by a clustered occurrence of basal cell carcinoma (white skin cancer). Apart from the constant development of new skin tumors, the course of this condition is different in each patient. Several major and minor criteria are used to diagnose Gorlin-Goltz syndrome.
What is Gorlin-Goltz syndrome?
Gorlin-Goltz syndrome is a largely unknown disorder due to its extreme rarity. The main symptom is the appearance of multiple benign and malignant skin tumors over the course of a lifetime. Other symptoms include jaw and skeletal anomalies, cleft lip and palate, or unusual skull shapes. According to preliminary surveys, approximately one in 56,000 people is affected by this disease. In Germany, about 100 patients are currently known. However, a larger number of unreported cases is suspected. Gorlin-Goltz syndrome was first described in 1960 by the US human geneticist Robert James Gorlin and the dermatologist Robert William Goltz. Other names for the disease are Gorlin’s syndrome, Hermans-Grosfeld-Spaas-Valk syndrome or Ward’s syndrome II. Regarding the symptoms, it is also called basal cell nevus syndrome or nevus epitheliomatodes multiplex. Both sexes are equally affected by the disease. Sometimes there is confusion in the descriptions with the so-called Goltz-Gorlin syndrome, which is also a genetic skin disease, but takes a completely different course. Moreover, in Goltz-Gorlin syndrome only females are affected, because male fetuses die already in the womb. From the fact that a similar name is used for both diseases, there may be irritation in the literature when describing them.
Causes
Several gene mutations may be responsible for Gorlin-Goltz syndrome. One known cause is a mutation of the tumor suppressor gene PTCH1 on chromosome 9. This gene provides control of the rate of profiling of certain cells (including basal cells). If this control is lost due to a mutation of the gene, new basal cell carcinomas can develop continuously. Since the profiling of other cells is also controlled, skeletal and jaw abnormalities form during embryogenesis. Furthermore, new jaw cysts may also continuously form in adulthood, which then need to be treated. In the womb, the so-called Hedgehog signaling pathway is responsible for normal embryonic development. However, this signaling pathway is normally switched off in adults because an increased rate of cell profiling is no longer necessary. However, due to a genetically modified PTCH1 gene, it can happen that this signaling pathway remains active. As a consequence, an increased cell formation rate, especially of the basal cells, is maintained. New skin tumors are constantly formed. Gorlin-Goltz syndrome is inherited in an autosomal dominant manner.
Symptoms, complaints, and signs
Gorlin-Goltz syndrome is essentially characterized by the appearance of ever-new basal cell carcinomas. The first skin tumors may appear before the age of 18. However, the main age of manifestation is between 30 and 50 years of age. From this point on, new tumors constantly appear, which do not form metastases but have a destructive effect on the neighboring bone and cartilage tissue. If left untreated, there is considerable disfigurement of the affected areas. There are patients who develop several thousand tumors during their lifetime. Mainly, the tumors are located on the face, head or back. There are usually anomalies in the vertebrae and ribs. Jaw cysts develop very frequently during life. Polydactyly (supernumerary fingers or toes), eye anomalies, fibromas of the heart or ovaries, cleft lip–piercing palate, deformities of the facial skull, cysts of the pleura, or medulloblastoma (malignant tumor of the cerebellum) in children may occur. Calcifications are found in the falx cerebri.
Diagnosis and course
Gorlin-Goltz syndrome can be diagnosed based on certain clinical criteria. There are major and minor criteria. For a confirmed diagnosis, either two major criteria or one major criterion and two minor criteria must be met.Major criteria include at least five basal cell carcinomas or one basal cell carcinoma before age 30, constant presence of jaw cysts, depressions on the palm of the hand or foot, abnormalities of the ribs, meningeal calcifications, or a family history of the syndrome. Secondary criteria include large head circumference, cleft lip and palate, abnormalities of the bones and spine, fibromas of the ovaries or heart, and medulloblastoma. Furthermore, human genetic testing can establish the diagnosis by detecting a mutation on gene PTCH1.
Complications
Gorlin-Goltz syndrome causes the development of skin cancer in most cases. This cancer can lead to various symptoms and complications, which depend greatly on the affected region and on the spread of the tumor disease. The tumor can also spread to bones and surrounding tissue and destroy it. This results in severe pain and limitation of movement. Various malformations can occur as a result of the tumors in the face. Often, the eyes are also affected, so that the patient may go blind or lose a significant part of his or her vision due to Gorlin-Goltz syndrome. The skull becomes deformed and cysts form in different parts of the body. Treatment of Gorlin-Goltz syndrome is usually done by surgically removing the tumor from the respective sites. Furthermore, medications are administered to the patient. However, there is no guarantee that the cancer will not recur later in life. The patient is equally dependent on attending preventive checkups to avoid a reduced life expectancy. Treatment of Gorlin-Goltz syndrome always results in a positive disease course in most cases.
When should you see a doctor?
If there are unusual skin abnormalities or changes in the usual skin appearance, a doctor must be consulted. If there is spotting on the skin, swelling, growths or lumps develop, a visit to the doctor is necessary. If the symptoms spread or increase in size, a doctor should be consulted as soon as possible. In Gorlin-Goltz syndrome, irregularities particularly affect the face, head and back. A visit to the doctor is necessary as soon as complaints of the bones, the back vertebrae or the cartilage tissue occur. If pain sets in or if movements are impaired, clarification of the complaints by a doctor is required. If open wounds occur on the body, sterile wound care is required. If this cannot be guaranteed, a doctor should be asked for help. In case of itching, a feeling of tension on the skin or inner restlessness, a doctor should be consulted. If the physical complaints lead to psychological problems, a visit to the doctor is also advisable. Depressive phases, mood swings as well as persistent melancholy are considered unusual. Aggressive behavior, changes in personality or social withdrawal are warning signs that should be followed up. A therapist is needed once the behavior continues for several weeks or months or it worsens.
Treatment and therapy
Therapy for Gorlin-Goltz syndrome consists of removal of basal cell carcinomas, orthopedic treatment for bone and vertebral abnormalities, surgical removal of jaw cysts, and oncopsychologic counseling. There are several options for the treatment of basal cell carcinoma. The first choice therapy is surgical removal of the tumor. This operation is performed under local anesthesia. In the process, healthy tissue is still operated on from the edge of the tumor at a safe distance in order to be able to remove as many tumor cells as possible. Furthermore, so-called cryotherapy is also used for some tumors. This involves icing the tumor with the aid of liquid nitrogen. An extremely cold spray is applied to the tumor, which then dies with the formation of a crust. As drug alternatives, imiquimod cream or 5-fluorouracil cream is applied to the tumor several times. Imiquimod cream activates the immune system so that it can locally cause the tumor to die. Treatment with 5-fluorouracil cream constitutes local chemotherapy. Finally, photodynamic therapy involves rubbing the tumor with a cream that makes the cancer cells very sensitive to light.
Outlook and prognosis
Gorlin-Goltz syndrome has a relatively poor prognosis. In most cases, the disease leads to skin cancer, which is often fatal. Accompanying complications and health problems are often severe, greatly reducing the quality of life and well-being of the affected individual. For example, the tumor may spread to the bones or neighboring tissues, resulting in restricted movement, pain and nerve disorders. In most cases, the affected person also goes blind and suffers various paralyses in the course of the disease. If the tumor is detected early, it may be possible to remove it before serious complications develop. A prerequisite for this, however, is that the patient undergoes a lengthy radiation therapy or a complicated operation, which in turn is associated with risks. Even with successful treatment, the patient is dependent on preventive examinations and drug therapy for the rest of his or her life. Thus, the outlook and prognosis depend primarily on when Gorlin-Goltz syndrome is detected and what measures are taken to remove the tumor. Generally, the earlier in life the tumor occurs, the better the prognosis. Older and sicker people have a slightly worse prognosis because the body often continues to break down as a result of treatment.
Prevention
Because Gorlin-Goltz syndrome is inherited in an autosomal dominant manner, affected families should seek human genetic counseling. Prenatal testing can detect Gorlin-Goltz syndrome.
Follow-up
The options for follow-up care are extremely limited in Gorlin-Goltz syndrome. Here, the patient is primarily dependent on direct medical treatment to prevent further complications. Self-healing cannot occur. Furthermore, a complete cure cannot be guaranteed, so that the life expectancy of the affected person may also be reduced. Early diagnosis and early treatment therefore play a very important role in Gorlin-Goltz syndrome. The syndrome is usually treated with the help of surgical interventions. After such interventions, affected persons should always rest and take care of their own bodies. If possible, strenuous activities or stressful activities should be avoided. Furthermore, medication can be taken to alleviate the symptoms of the syndrome. Care should be taken to ensure that the medication is taken regularly and that it may interact with other medications. In some cases, those affected are also dependent on chemotherapy. In this case, the support of friends or family is also very helpful and can accelerate the healing process. Contact with other sufferers can also be very useful in this regard.
What you can do yourself
In Gorlin-Goltz syndrome, there are no particular self-help options available to the patient. As a rule, the tumors must always be removed by medical treatment in this case. However, since Gorlin-Goltz syndrome is inherited, patients or their parents should always undergo genetic counseling. This may help prevent the syndrome from occurring in future generations. The tumors are removed by surgery. In some cases, various creams may also be used to fight the tumor. Often, those affected depend on psychological support. This should be provided primarily by a therapist or close friends and by family. Support in everyday life can also have a positive effect on the course of the disease. The affected person can be accompanied to medical examinations or treatments or supported during longer stays in a hospital. In the case of psychological complaints, discussions with close relatives and friends are always very helpful. Contact with other patients of Gorlin-Goltz syndrome may also prove helpful. Children should always be informed about the possible consequences and complications of the disease.