Gorlin -Goltz syndrome is a very rare genetic disease characterized by an increased occurrence of basalioma (white skin cancer). Apart from the constant emergence of new skin tumors, the course of this condition is different for each patient. Various main and secondary criteria are used to diagnose Gorlin-Goltz syndrome.

What is Gorlin-Goltz Syndrome?

Due to its extreme rarity, Gorlin-Goltz syndrome is a largely unknown disease. The main symptom is the occurrence of several benign and malignant skin tumors in the course of life. Other symptoms include jaw and skeletal abnormalities, cleft lip and palate, or unusual skull shapes.

According to abbreviationfinder.org, approximately one in 56,000 people is affected by this disease. Around 100 patients are currently known in Germany. However, a larger number of unreported cases is suspected. The Gorlin-Goltz syndrome was first described in 1960 by the American human geneticist Robert James Gorlin and the dermatologist Robert William Goltz.

Other names for the condition are Gorlin syndrome, Hermans-Grosfeld-Spaas-Valk syndrome or Ward’s syndrome II. With regard to the symptoms, the term basal cell nevus syndrome or nevus epitheliomatodes multiplex is also spoken of. 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. In addition, Goltz-Gorlin syndrome only affects women because male fetuses die in the womb. The fact that a similar name is used for both diseases can lead to confusion in the description in the literature.

Causes

Several gene mutations can be responsible for Gorlin-Goltz syndrome. A mutation of the tumor suppressor gene PTCH1 on chromosome 9 is known. This gene controls the proliferation rate of certain cells (including the basal cells). If this control is lost due to a mutation in the gene, new basal cell carcinomas can constantly develop.

Since the proliferation of other cells is also controlled, skeletal and jaw anomalies develop during embryogenesis. Furthermore, jaw cysts can constantly form in adulthood, which then have to be treated. In the womb, the so-called hedgehog signaling pathway is responsible for the normal development of the embryo.

However, this signaling pathway is normally switched off in adults because an increased proliferation rate of the cells is no longer necessary. However, a genetically modified PTCH1 gene can cause this signaling pathway to continue to be active. As a result, an increased rate of cell formation, especially of the basal cells, remains. New skin tumors are constantly forming. Gorlin-Goltz syndrome is inherited in an autosomal dominant manner.

Symptoms, Ailments & Signs

The Gorlin-Goltz syndrome is essentially characterized by the appearance of new basal cell carcinomas. The first skin tumors can appear before the age of 18. However, the main age of onset 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 adjacent bone and cartilage tissue. If left untreated, there will be significant disfigurement in the affected areas. There are patients who develop thousands of tumors during their lifetime.

The tumors are mainly located on the face, head or back. There are usually abnormalities in the vertebrae and ribs. Jaw cysts develop very commonly throughout life. Polydactyly (extra fingers or toes), eye abnormalities, fibroids of the heart or ovaries, cleft lip and palate, deformities of the facial skull, cysts of the pleura or a medulloblastoma (malignant tumor of the cerebellum) in children can occur. Calcifications are found in the falx cerebri.

Diagnosis & History

The diagnosis of Gorlin-Goltz syndrome can be made based on certain clinical criteria. There are main and secondary criteria. For a reliable diagnosis, either two main criteria or one main criterion and two secondary criteria must be met.

The main criteria include at least five basaliomas or one basalioma before the age of 30, constant occurrence of jaw cysts, dents on the palms of hands or feet, anomalies on the ribs, meningeal calcifications or the family history of the syndrome.

Additional criteria are large head circumference, cleft lip and palate, anomalies in the bones and spine, fibroids in the ovaries or heart, and medulloblastoma. Furthermore, the diagnosis can be made by detecting a mutation in the gene PTCH1 through a human genetic test.

Complications

In most cases, skin cancer develops as a result of Gorlin-Goltz syndrome. This cancer can lead to various symptoms and complications, which depend heavily on the affected region and the spread of the tumor disease. The tumor can also spread to and destroy bone and surrounding tissue.

This causes severe pain and restricted movement. Various malformations can occur as a result of tumors on the face. The eyes are often also affected, so that the patient can go blind or lose a significant part of their vision as a result of Gorlin-Goltz syndrome. The skull is deformed and cysts form in different parts of the body.

Gorlin-Goltz syndrome is usually treated by surgically removing the tumor from the affected area. Medications are also administered to the patient. However, there is no guarantee that the cancer will not recur in later life.

The patient is also dependent on attending check-ups so that life expectancy is not reduced. In most cases, the treatment of Gorlin-Goltz syndrome always results in a positive course of the disease.

When should you go to the doctor?

A doctor must be consulted in the event of unusual skin abnormalities or changes in the usual complexion. If there are spots on the skin, swelling, growths or lumps, a doctor’s visit is necessary. If the symptoms spread or increase in size, a doctor should be consulted as soon as possible. In Gorlin-Goltz syndrome, the face, head and back are particularly affected by irregularities.

A doctor’s visit is necessary as soon as there are complaints of the bones, the vertebrae or the cartilage tissue. If pain sets in or if movement is impaired, the complaints need to be clarified by a doctor. If there are open wounds 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 tightness on the skin or an inner restlessness, a doctor should be consulted. If the physical symptoms lead to psychological problems, it is also advisable to see a doctor.

Depressive phases, mood swings and persistent melancholy are considered unusual. Aggressive behavior, personality changes, or social consideration are red flags that should be followed up. A therapist is needed if the behavior persists for several weeks or months or if it worsens.

Treatment & Therapy

Therapy for Gorlin-Goltz syndrome consists of removal of the basalioma, orthopedic treatment for bone and vertebral anomalies, surgical removal of jaw cysts, and oncopsychological consultations. There are several options for treating basalioma.

The first line of therapy is surgical removal of the tumor. This operation is performed under local anesthesia. Healthy tissue is 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, the so-called cryotherapy is also used for some tumors.

This involves freezing the tumor using liquid nitrogen. An extremely cold spray is sprayed onto the tumor, which then dies with crust formation. As drug alternatives, imiquimod cream or 5-fluorouracil cream is applied to the tumor several times.

The imiquimod cream activates the immune system so that it can kill the tumor locally. Treatment with 5-fluorouracil cream represents local chemotherapy. Finally, in photodynamic therapy, the tumor is rubbed with a cream that makes the cancer cells very sensitive to light.

Outlook & Forecast

Gorlin-Goltz syndrome has a relatively poor prognosis. In most cases, the disease leads to skin cancer, which is often fatal. This is often accompanied by serious complications and health problems that greatly reduce the quality of life and well-being of those affected. The tumor can spread to the bones or adjacent tissue, which can lead to restricted movement, pain and nerve disorders. In most cases, those affected also go blind and suffer from various types of paralysis in the course of the disease.

If the tumor is detected early, it may be removed before serious complications develop. The prerequisite for this, however, is that the patient undergoes lengthy radiation therapy or a complicated operation, which in turn involves risks. Even if the treatment is successful, the patient is dependent on preventive examinations and drug therapy for the rest of his life.

So the outlook and prognosis depend primarily on when Gorlin-Goltz syndrome is diagnosed and what measures are taken to remove the tumor. Basically, the prognosis is better the earlier in life the tumor occurs. Elderly and sick people have a slightly poorer prognosis, as the body often continues to break down as a result of treatment.

Prevention

Since the Gorlin-Goltz syndrome is inherited in an autosomal dominant manner, affected families should seek genetic counseling. Gorlin-Goltz syndrome can be detected with a prenatal examination.

Aftercare

Aftercare options are extremely limited in Gorlin-Goltz syndrome. The patient is primarily dependent on direct medical treatment to prevent further complications. Self-healing cannot occur.

Furthermore, complete healing cannot be guaranteed, which means that the life expectancy of those affected may 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 procedures, those affected should always rest and protect their own bodies. Strenuous activities or stressful activities should be avoided as far as possible. You can also take medication to counteract the symptoms of the syndrome.

Regular intake and possible interactions with other medicines should be taken into account. In some cases, those affected also need chemotherapy. The support of friends or family is also very helpful and can speed up healing. Contact with other people affected can also be very useful.

You can do that yourself

With Gorlin-Goltz syndrome, the patient has no special options for self-help. The tumors usually have to be removed by medical treatment. However, since Gorlin-Goltz syndrome is inherited, patients or their parents should always seek genetic counseling. This may prevent the syndrome from occurring in future generations.

The tumors are removed surgically. In some cases, various creams that fight the tumor can also be used. Those affected often need psychological support. This should be done primarily by a therapist or close friends and family.

Support in everyday life can also have a positive effect on the course of the disease. The person concerned can be accompanied to medical examinations or treatments or be supported during longer stays in a hospital.

In the case of psychological problems, it is always very helpful to talk to close relatives and friends. Contact with other patients of Gorlin-Goltz syndrome can also prove to be helpful. Children should always be informed about the possible consequences and complications of the disease.