Gardner's syndrome symptoms. Gardner's syndrome is a dangerous pathology that requires urgent treatment. Are complications possible?

Gardner's syndrome

© Edward Czerny

Vanderbilt University, USA, Tennessee, Nashville

G Gardner's syndrome is rare disease, the frequency of which is approximately 1 in 22,000. Most cases result from autosomal dominant inheritance due to mutations in the APC (Adenomous Polyposis Coli) gene. However, about 20% of cases occur spontaneously. Clinically, the lesions can vary in size and pigmentation, but many have a fishtail appearance. One histological study showed changes that were more widespread than expected. clinical picture, and one case in this study showed hamartoma-like changes. While foci of congenital hypertrophy pigment epithelium Gardner's syndrome is histologically similar to isolated lesions of congenital pigment epithelial hypertrophy and grouped pigment epithelial nevi ("bear tracks"), both of which are benign and have no association with polyps or colon cancer.

G Key words: Gardner's syndrome; "fish tail"; “bear tracks”; congenital hypertrophy of the pigment epithelium.

UDC 617.735 GRNTI 76.29.56 VAK 01/14/07

Gardner syndrome is a dominantly inherited adenomatous intestinal polyposis with a predominant lesion of the colon. It was first described in 1950 as a description of the defeat of one family, all of whom were descendants of the same married couple. On the father's side, there is a family history of oncological diseases did not have. The mother (proband) died of colon cancer and 9 of her 45 offspring in two different generations also died of colorectal cancer. Soon after this publication, a combination with this syndrome of other pathological conditions was discovered, for example, osteomas of the skull bones, fibromas, lipomas and cysts sebaceous glands. Subsequently, a connection was also revealed between Gardner’s syndrome and desmoid tumors and abnormalities of dental structure

Polyps are usually detected in the second half of the second decade of life, and they usually become malignant approximately 15 years after diagnosis. The risk of developing colon cancer is almost 100%, with 50% of patients developing colon cancer by age 35. Other malignant neoplasms may include carcinomas of the adrenal gland, thyroid gland and Bladder. Turcot syndrome develops in patients who also have neuroepithelial tumors.

The ocular manifestations of Gardner's syndrome were first described by Blair and Trempe in 1980. The authors examined nine family members with Gardner syndrome. Three family members out of 9, mother

and her two daughters, there was hypertrophy of the pigment epithelium. They all had polyps in their colon. One patient had five lesions on the right eye and 12 on the left eye. The lesions had an oval or round shape, their size was about 2 disc diameters optic nerve. The second patient had four lesions in one eye and one in the other eye. The mother of both of these patients had four lesions in the right eye and six in the left eye. In all patients, the lesions were randomly located on the fundus, without forming any clusters.

While in a number of families with Gardner's syndrome there are no retinal changes, the detection of three or more foci of congenital pigment epithelial hypertrophy indicates a high likelihood of intestinal polyposis. Therefore, in those families. in which there is a history of polyposis, careful examination of the retina and identification of typical lesions of congenital pigment epithelial hypertrophy can help identify patients at high risk for the disease. However, the absence of eye involvement does not mean that the patient will not develop intestinal polyposis. Lesions in the fundus can have different sizes, shapes and pigmentation; however, many lesions have a fishtail appearance (Figs. 1 and 2).

Shields et al. studied data from 132 patients diagnosed with congenital hypertrophy of the pigment epithelium, identifying both isolated lesions and those grouped with severe pigmentation (“bear tracks”). One patient had intestinal polyposis, without malignancy. Of the 2,000 blood relatives of these patients, only 20 had polyposis or colon cancer. had

Rice. 1, 2. This 13-year-old girl has multiple lesions in both eyes. Her grandfather and mother had colon cancer. The patient herself did not have polyposis at the time of the examination, but she needs close monitoring

polyposis or colonic cancer. This one percent incidence was significantly lower than expected if these lesions were associated with familial adenomatous polyposis within Gardner syndrome.

Traboulsi and Murphy examined the eyes of patients with Gardner's syndrome histologically. Most of the outbreaks histological structure were similar to other lesions in congenital hypertrophy of the pigment epithelium. The pigment epithelial cells were increased in size and filled with round pigment granules. The photoreceptors located above the lesions were partially atrophied. The authors also found several other types of lesions; one of them appeared similar to a hamartoma and extended from the pigment epithelium through the inner layers of the retina, and the other type represented areas of cell hypertrophy.

bibliography

1. Gardner E.J., Stephens F.E. Cancer of the lower digestive tract in one family group. //Am. J.Hum. Genet. - 1950. - March, Vol. 2 (1). - P. 41-48.

2. Gardner E. J., Richards R. C. Multiple cutaneous and subcutaneous lesions occurring simultaneously with hereditary polyposis and osteomatosis. //Am. J.Hum. Genet. - 1953. - Vol. 5. - P. 139-147.

3. Fader M., Kline S. N., Spatz S. S., Zubrow H. J. Gardner's syndrome (intestinal polyposis, osteomas, sebaceous cysts) and a new dental

4. Asman H. B. Pierce E. R. Familial polyposis. A statistical study of a large Kentucky kindred Cancer. // 1970, Apr. 25(4). - P. 972-981.

5. Gardner E. J., Burt R. W., Freston J. W. Gastro-intestinal polyposis: syndromes and genetic mechanisms. //West. J. Med. - 1980. - Vol. 132. - P. 488-499.

6. Blair N. P., Trempe C. L. Hypertrophy of the retinal pigment epithelium associated with Gardner's syndrome. // Am. J. Ophthalmol. - 1980. - Vol. 90. - P. 661-667.

7. Lewis R. A., Crowder W. E., Eierman L. A., Nussbaum R. L., Ferrell R. E. The Gardner syndrome: significance of ocular features. // Ophthalmology. - 1984. - Vol. 91. - P. 916-925.

8. Shields J. A., Shields C. L, Shah P. G., Pastore D. J. Imperiale SM Jr.: Lack of association amonh typical congenital hypertrophy of the retinal pigment epithelium, adenomatous polyposis and Gardner syndrome. // Ophthalmology. - 1992. - Nov, Vol. 99(11). - P. 1709-1713

9. Traboulsi E. I., Murphy S. F, de la Cruz Z. C, Maumenee I. H, Green W. R. A clinicopathologic study of the eyes in familial adenomatous polyposis with extracolonic manifestations (Gardner's syndrome). // Am. J. Ophthalmol. - 1990. - Nov, Vol. 15, 110(5). - P. 550-561.

Gardner's syndrome

G Key words: "fish tail"; "bear tracks"; congenital pigment epithelium hypertrophy

Cherny Edward - professor. Eye Institute, Vanderbilt University, Tennessee, Nashville, USA. 2311 Nashville, NY Tennessee, USA. Email: [email protected].

Cherney Edward- Edu Associate Professor of Ophthalmology Vanderbilt Eye Institute. Vanderbilt University. 2311 Pierce Avenue, Nashville, TN, 37232, USA. Email: edward.cherney@Vanderbilt.

Gardner's syndrome, also known as Gardner's syndrome or familial colorectal polyposis, is a subtype of FAP. Gardner's syndrome is an autosomal dominant form of polyposis characterized by the presence of multiple polyps in the colon along with tumors outside the colon. The extracolonic tumors may include osteoma of the skull, thyroid cancer, epidermoid cysts, fibromas, and the occurrence of desmoid tumors in approximately 15% of affected individuals.

Desmoid tumors are fibrous tumors that usually arise in the tissue lining the intestine and can be caused by surgery to remove the colon. Countless polyps in the colon predispose to the development of colon cancer; If the colon is not removed, then the possibility of developing colon cancer is considered very important. Polyps can also grow in the stomach, duodenum, spleen, kidneys, liver, mesentery and small intestine. In a small number of cases, polyps also appeared in the cerebellum. Cancers associated with Gardner's syndrome often appear in the thyroid, liver, and kidneys. The number of polyps increases with age, and hundreds to thousands of polyps can develop in the colon.

The syndrome was first described in 1951. There is no treatment currently, and in its more advanced forms, it is considered a terminal diagnosis with a life expectancy of 35–45 years; procedures include surgery and palliative care, although some chemotherapy has been tried with limited success.

genetics

Gardner syndrome is inherited in an autosomal dominant manner. Typically, one parent has Gardner syndrome. Each of their children, male and female, are at 50% risk of inheriting the Gardner syndrome gene.

cause

Gardner's syndrome is caused by a mutation in the adenomatous polyposis coli (APC gene), located on chromosome 5q21 (band Q21 on chromosome 5). This gene is also mutated in FAP, a more common disease that also predisposes to colon cancer. Nuances in understanding genetics have caused some disorders to be shared across multiple individuals, while others are combined into a single genetic condition. After much of the second half of the 20th century, Gardner syndrome was combined into FAP and is now considered simply the phenotypic subtype F. FAP is defined by the development of hundreds or thousands of polyps in the colon. Gardner's syndrome is identified separately as a subtype because, in addition to colonic polyps, there are also extra-intestinal neoplasms (both malignant and benign). There are many terms used to describe the "APC-associated polyposis condition" including FAP, attenuated FAP, Gardner's syndrome, Turcot's syndrome, and gastric adenocarcinoma and proximal gastric polyposis (GAPPS). There is a movement to no longer use the terms Gardner syndrome or Turcot syndrome, as they are part of the FAP spectrum. Gardner's syndrome and Turcot's syndrome are discussed primarily for historical interest.

diagnostics

Gardner's syndrome consists of adenomatous polyps of the gastrointestinal tract, desmoid tumors, osteomas, epidermoid cysts, lipomas, dental anomalies and periampullary carcinomas. The frequency of the syndrome is 1:14025 with an even gender distribution. It is determined by the autosomal dominant gene for familial polyposis coli (APC) on chromosome 5.

Gardner's syndrome can be identified based on oral findings, including multiple affected and supernumerary teeth, multiple osteomas of the jaw that give a "wool-like" appearance appearance sponges, as well as several odontomas, congenital hypertrophy of the retinal pigment epithelium (CHRPE), in addition to several adenomatous polyps of the colon. Gardner's syndrome is also associated with SAP and may manifest as a desmoid tumor from the retroperitoneum.

Desmoid tumor most often arises from the aponeurosis of the rectus abdominis muscle of multiparous women. The extra-abdominal form is rare and mammary desmoids may arise in the mammary gland or may occur as an extension of a lesion arising from the muscles of the chest wall. The incidence of desmoid breast tumors is less than 0.2% of primary breast tumors. With Gardner's syndrome, the incidence ranges from 4% to 17%. Desmoid tumors associated with Gardner syndrome have been shown to have an alteration in the β-catenin pathway and again express beta-catenin.

treatment

There is no cure for Gardner's syndrome. Treatment focuses on relieving symptoms and reducing the risk of cancer. Treatment for desmoid tumors may include surgery, NSAIDs, anti-estrogen drugs, radiation therapy and chemotherapy.

Among skin manifestations pathological process the most common are atheromas. The disease was named in honor of its discoverer, doctor E. Gardner.

Causes of Gardner's syndrome

Cause of Gardner's syndrome is a hereditary predisposition that is inherited in an autosomal dominant manner. Thus, the patient inherits gene mutations from his parents, which leads to the formation of adenomatous polyps in the thin and. That is why the disease is also called familial adenomatous polyposis.

Symptoms of Gardner's syndrome

Main symptoms of Gardner's syndrome caused by the appearance of adenomatous polyps in the intestine. Most often, the pathological process is localized in the colon, but in some cases, polyps can also be found in the duodenum. Most often, neoplasms appear during puberty. By the age of 25-30, the risk of malignancy of adenomatous polyps increases significantly. The risk of transmitting mutant genes from parent to child is about 50%.

With small tumors, the patient may have nothing to worry about. In more severe cases there is intestinal bleeding, concomitant iron deficiency anemia, obstructive intestinal obstruction. Skin manifestations of Gardner's syndrome include atheromas, fibromas, osteomas, and lipomas. These neoplasms are benign tumors localized in soft tissues. Most often they are tumor-like formations that can cause some painful sensations in case of compression of nerve fibers. Also for this pathological condition characterized by early tooth loss.

In more than 90% of cases, adenomatous polyps in patients with Gardner syndrome become malignant. This is why early detection of signs of a malignant process is so important. At the same time, attention is paid to the appearance of stool disorders, disturbances in the shape of the stool and the act of defecation. In some cases, patients may experience such general symptoms such as weakness, fatigue, loss of appetite and body weight. The appearance of such pathological signs should alert you and force you to consult a doctor.

Diagnosis of Gardner's syndrome in Israel

If a patient is suspected of having Gardner's syndrome, the following diagnostic tests are performed:

• blood analysis– allows you to identify signs iron deficiency anemia, exclude other diseases;
• stool analysis– necessary to determine hidden bleeding;
• – This endoscopic examination allows you to examine most of the colon. When it is carried out, polyps may be detected, indicating the presence of the disease;
• biopsy– performed during a colonoscopy. In this case, samples of polyp tissue are taken with a special device. When studying the material in the laboratory, a conclusion can be made about the nature of the pathological process;
• irrigoscopy is an x-ray examination in which a contrast agent is injected into the gastrointestinal tract. By taking a series of images, you can evaluate the contrast distribution through the intestines and visualize polyps;
• radiography and scintigraphy of skeletal bones– aimed at identifying tumors bone tissue. Most often, pathological neoplasms in Gardner syndrome are localized in the area of ​​the upper and lower jaws.

Treatment of Gardner's syndrome in Israel

The most effective and radical way to treat Gardner's syndrome is endoscopic polypectomy. When carrying out such an intervention, no violation of the integrity is required skin. All manipulations are carried out endoscopically, by introducing devices into the anus. The use of general anesthesia allows you to reduce discomfort from carrying out the procedure to a minimum. Using an endoscopic device, the surgeon examines the inner surface of the mucous membrane of the colon. The device is equipped with a video camera, so everything that happens inside can be seen on the monitor screen. Once polyps are detected, they are easily removed using a special loop and removed.

However, endoscopic polypectomy may not be suitable for all patients. If malignant cells are detected based on the results of a biopsy, abdominal surgery is indicated. In this case, resection of part of the intestine is performed, followed by anastomosis. This makes it possible to most radically eliminate the focus of the pathological process and prevent recurrence. In some cases, a total colectomy is indicated. This surgical intervention is aimed at complete removal colon. During this procedure, a significant part of the intestine is resected, which subsequently requires an ileostomy or ileorectal anastomosis.

If the patient refuses radical surgery, endoscopic polypectomy can be performed. If during histological examination If no malignant cells are detected from the removed tumors, the patient is advised to undergo dynamic monitoring with regular colonoscopy. If complications such as intestinal bleeding and obstructive intestinal obstruction develop, emergency surgical interventions are performed.

For patients with Gardner's syndrome, medical genetic counseling is important to reduce the risk of testing the disease in a future child. Modern technologies in vitro fertilization are aimed at selecting the most complete embryos without genetic disorders.

With proper and timely treatment, the prognosis for patients with Gardner syndrome is favorable.

Gardner's syndrome is one of the types of familial (hereditary) polyposis, including the presence of numerous polyps in the colon, osteomas and tumors, epidermal cysts, as well as epithelial hyperplasia of the retinal pigment.

This is a precancerous disease that predetermines malignant tumors in more than 70% of cases. Therefore, patients with Gardner's symptoms require constant health monitoring.

Facts about Gardner's sign

Gardner syndrome is of autosomal dominant origin. Most cases are associated with a mutation in the APC gene. The disease can also occur spontaneously as a result of damage to the RAS gene on chromosome 12, damage to the p53 gene on chromosome 17, or loss of DNA methylation.

The incidence of familial adenomatous polyposis is about 1/10,000 cases of live births and occurs equally in both sexes. Gardner's syndrome is much less common, but the possibility of this condition cannot be excluded during diagnosis.

In the case of familial adenomatous polyposis and its variant - Gardner's syndrome, it is important that the whole family is under the supervision of specialists and quickly receives medical care and genetic counseling.

Symptoms of Gardner's Syndrome

• Numerous adenomatous polyps of the colon. An intestinal polyp is a protrusion of the mucous membrane above the surface directed towards the intestinal lumen. The most common type of polyp found in adults is adenomatous, associated with the growth of glandular epithelial cells. Polyps are the precursors of cancerous changes. In Gardner's syndrome, they also occur in the stomach and small intestine.
• Desmoid tumors. Such tumors are located retroperitoneally or in the intestinal mesentery and are usually harmless. They appear after proctocolectomy and occur in 10% of patients with hereditary colon polyposis. Desmoid tumors, although benign, are not harmless. They can grow rapidly, compressing surrounding organs and consequently leading to organ failure.
• Retinal degeneration.A characteristic change in this syndrome is retinitis pigmentosa. Most patients experience eye changes, such as discoloration of the oval.

These symptoms are diagnostically important because they are present from birth or appear slightly later and can be detected quickly. Other signs of Gardner's syndrome, especially those related to the digestive tract, are revealed later.

Additional symptoms:

• Mesodermal tumors, such as osteomas located in the lower jaw and skull bones. They may precede other symptoms and therefore may be markers of changes caused by intestinal polyposis.
• Epidermal cysts. Gardner's syndrome is characterized by the presence of multiple epidermal cysts and fibroids on the skin of the face and scalp.

Symptoms that the patient may observe are intestinal disorders. The most important symptom of Gardner's syndrome is a change in the rhythm of bowel movements, constipation. The main symptoms that appear from the age of 10 are: diarrhea, abdominal pain, mucous stool, rectal bleeding. However, the course of Gardner's syndrome is usually uncharacteristic.

Gardner's syndrome contributes to cancer

In untreated cases, polyps of the colon and duodenum are often malignant. But the disease also leads to other types of cancer.

Patients with Gardner's syndrome often have:

• medulloblastomas;
• craniopharyngiomas;
• thyroid cancer;
• osteosarcomas and chondrosarcomas;
• liposarcoma;
• malignant liver tumors.

Diagnostics

To make such a complex diagnosis requires comprehensive assessment all symptoms. The doctor must examine the condition of the mucous membrane of the stomach, thyroid gland, retina, skull bones, skin and teeth.

First of all, patients' intestines are examined. Polyps can cover the entire surface of the colon; isolated specimens are found in the stomach and small intestine. This sign can be detected during examination already during adolescence. Patients usually notice obvious symptoms by the age of 40. Unfortunately, patients with confirmed Gardner's syndrome who have colon polyps are almost 90% susceptible to colon cancer.

The main type of research for such patients is colonoscopy . This examination allows you to remove polyps and take tissue for histopathological examination. Based on the results of the colonoscopy, the doctor makes a diagnosis of malignancy. A timely procedure saves lives.

Osteomas can be detected at the angle of the lower jaw, on the skull, near the paranasal sinuses and in long bones. Osteomas can be identified usingcomputed tomographyshowing the position and size of the formations.

In addition to polyps, the presence of Gardner's syndrome is indicated by the presence of epidermoid cysts, desmoid tumors, and pigmentary changes in the retina.

Since patients are at risk for different types cancer, they need regular screening for the presence of papillary thyroid cancer, adenocarcinomas, adrenal adenomas, osteosarcomas, chondrosarcomas, hepatocellular cancer and others malignant tumors in the thyroid gland and liver.

Treatment of Gardner's syndrome

Drug treatment.Is not the main one. The doctor prescribes:

• , preventing the transition of colorectal polyps to carcinoma. These medications reduce the size and number of polyps in some patients. But this does not exclude the development of new tumors and malignant degeneration of existing polyps.
• COX-2 inhibitors, reducing the size of polyps. How they affect cancer development is not yet known.

Surgical treatment:

• For patients with Gardner's syndrome, prophylactic colectomy, which is partial or complete surgical removal of the colon, is recommended. The patient's condition is then carefully monitored.
• For stomach polyps, while the disease is not advanced, a small polypectomy gives a good result.
• A restorative proctocolectomy may be performed. In this case, the colon mucosa is removed, intestinal functions are preserved, but an ileostomy is temporarily necessary.

During conservative therapy and after surgery, endoscopic examination of the small and large intestine should be performed regularly to monitor changes in the intestine. The liver and thyroid gland are examined using ultrasound.

Gardner's syndrome is a form of familial adenomatous polyposis (FAP) that is characterized by multiple colorectal polyps, various types of tumors, both benign (non-cancerous) and malignant (cancerous).

People with Gardner's syndrome have high risk development of colorectal cancer in early age. They are at increased risk of developing other FAP-related cancers, such as colon, stomach, pancreas, thyroid, central nervous system, liver, bile ducts, adrenal glands.

Other signs include:

• dental anomalies; osteomas ( benign neoplasms bones);
• various skin abnormalities such as epidermoid cysts, fibromas ( benign tumor connective tissue), lipomas;
• desmoid tumors.

Caused by changes in the APC gene. It is inherited in an autosomal dominant manner. Although there is no cure for Gardner's syndrome, there are options to help reduce your risk of developing cancer. These may include specific screening, preventive surgical operations, some types of medications.

Other names:

• Polyposis coli, multiple tumors of hard and soft tissues;
• Intestinal polyposis, osteomas, sebaceous cysts.

With Gardner's syndrome, symptoms vary from person to person. This is a form of familial adenomatous polyposis (FAP). It is characterized primarily by hundreds or thousands of indistinct (benign) polyps in the colon that begin to appear by age 16.

If not removed, these polyps will become malignant (cancerous), leading to early onset cancer at age 39.

Other Features

• Dental abnormalities;
• Adenomatous polyps of the stomach, small intestine;
• Osteomas (benign bone tumors);
• Congenital hypertrophy of the retinal epithelium (a flat pigmented spot on the outer layer of the retina);
• Benign skin abnormalities such as epidermoid cysts, fibromas (benign connective tissue tumors), lipomas;
• Adrenal problems;
• Desmoid tumors;
• (small intestine, stomach, pancreas, thyroid, Central nervous system, liver, bile ducts, adrenal glands).