What is Gardner Syndrome?
Gardner syndrome is a type of familial adenomatous polyposis, a genetic condition that can be passed down through families. This condition is distinguished by the presence of growths, called polyps, in the colon, as well as other changes outside the colon. These can include a type of benign tumor known as an osteoma, cysts on the skin, and other abnormal growths such as desmoid tumors.
People with Gardner syndrome can have osteomas or growths in the jaw and skull, cysts in the skin, and fibers growing into tissues, which usually doesn’t cause any noticeable symptoms. However, these can lead to complications such as itchiness, inflammation, and bursting of the cysts.
In addition, people with this syndrome often show changes that aren’t related to the skin. A common sign is the presence of benign dark spots in both eyes, a condition known as congenital hypertrophy of the retinal epithelium.
Gardner syndrome often leads to the development of many polyps in the bowels and colorectal cancer. Furthermore, other forms of cancer have also been reported such as cancer in the small intestine, liver cancer, adrenal gland tumors, and a type of thyroid cancer called papillary or follicular thyroid cancer.
What Causes Gardner Syndrome?
Research has found a genetic connection to the development of Gardner syndrome, a disease characterized by the growth of non-cancerous tumors and various types of skin and bone growths. This connection is traced to a particular region known as 5q21 on chromosome 5, which is home to a gene that tries to prevent tumors from forming, known as adenomatous polyposis coli (APC).
This APC gene is crucial in controlling the growth of cells by ensuring the cells grow and divide at the right time. However, patients with Gardner syndrome have a flaw in this gene, which results in cells growing uncontrollably. Detailed studies of this gene have found that the most common flaws are nonsense mutations, which lead to the formation of a shortened version of the protein that APC gene should usually produce. Most of these mutations are found at one end of the gene. Specific parts of the gene, such as areas denoted by codons 1403 to 1578, seem to be more closely tied to the formation of lesions in the lower jaw. Those that lie beyond codon 1444 are associated with a two-fold increased chance in the formation of benign bone tumors called osteomas.
Besides these problems in the APC gene, Gardner syndrome has also been linked to a loss of DNA methylation (a process that controls gene activity), a mutation in the RAS gene on chromosome 12, a deletion of a gene linked to colon cancer (DCC) on chromosome 18, and a mutation in the gene TP53 located on chromosome 17. It is worth mentioning that if one of your parents has Gardner syndrome, you have a 50% chance of inheriting it – this is known as autosomal dominant inheritance. Once the gene is inherited, it almost certainly leads to the disease – a characteristic described as near-complete penetrance.
Risk Factors and Frequency for Gardner Syndrome
Gardner syndrome is a condition that varies in occurrence, with recent studies suggesting it affects about 1 in 7000 to 1 in 30,000 births. The disease occurs equally in men and women due to its dominant inheritance pattern, but it can show up differently in different people. Up to 30% of people with the condition don’t have a family history of it. It’s also important to note that Gardner syndrome is one specific type of a larger group of diseases known as familial adenomatous polyposis.
Signs and Symptoms of Gardner Syndrome
Gardner syndrome is a condition that can vary quite a bit from person to person because of the differences in each person’s genetic makeup. But one common sign of this condition is developing a large number of polyps (small, benign growths) in the intestines. Often, this condition is diagnosed as doctors are looking for other types of diseases or during regular check-ups. However, there are some specific signs that may suggest someone has this condition.
People with Gardner Syndrome may experience several intestinal problems such as diarrhea, stomach cramping, pain or bleeding from the rectum, and vomiting. If the intestine gets blocked, they could also experience constipation. There are other signs of Gardner Syndrome that don’t involve the intestinal tract. These can include:
- Osteomas (bony growths) often found in the jaw, skull, and long bones
- Lipomas (fatty growths)
- Epidermal inclusion cysts (skin cysts)
- Desmoid tumors (soft tissue growths)
- Dental abnormalities, such as extra teeth
- Fibromatosis
- Pilomatricomas (skin condition with multiple lesions, and having six or more is linked to Gardner Syndrome)
- Adrenal adenomas (nodules on adrenal glands which could be linked to a condition called hyperaldosteronism)
- Congenital hypertrophy of the retinal pigment epithelium, a condition that affects the eye
Almost all (93%) patients with Gardner syndrome show radioopaque (visible on an x-ray) lesions in the jaw. Although most of the symptoms of Gardner syndrome are benign (not harmful), regular medical checkups are crucial because it is linked to different types of cancer. The most common is colorectal cancer which often shows up early in patients with this syndrome and may be the first hint that they have Gardner syndrome. Another condition requiring further evaluation is Desmoid fibromatosis, a nonmetastatic (doesn’t spread) soft tissue tumor which could have potential implications. Other forms of cancer associated with Gardner Syndrome include thyroid cancer, cancer of rectal glands (adenocarcinoma), common bile duct adenomas, and medulloblastomas (a type of brain tumor).
Testing for Gardner Syndrome
Gardner syndrome is a condition that can be tough to identify and assess because it presents in many different ways, not only affecting the intestines but other parts of the body as well. While the most common symptom is the growth of numerous benign polyps in the colon, the condition is often detected because of signs appearing outside the intestines. These symptoms can show up at any time, from two months old to as late as 70 years, but they typically start appearing during teenage years. When doctors suspect this syndrome because of these various symptom, they can confirm it with genetic testing.
When checking for Gardner syndrome, here are a few important steps that the doctor takes:
Skin: The doctor conducts a thorough examination of your skin and, if necessary, may take small samples of any skin growths like cysts, fibromas, lipomas, leiomyomas, or pilomatricomas to examine under a microscope (a procedure known as histopathology).
Soft Tissue: If the doctor suspects you have ‘desmoid tumors’ (aggressive non-cancerous growths that occur in the connective tissues of your body) which are more common in people with Gardner syndrome, they will use techniques like magnetic resonance imaging (MRI) and ultrasound to make sure these are not affecting other organs in your body.
Thyroid: To monitor any abnormalities in your thyroid, the doctor will conduct a holistic examination and an annual ultrasound.
Eye: Regular eye check-ups involving ‘slit-lamp’ and ‘ophthalmoscopic’ examinations are done to check for unusual growth in the retina, the layer at the back of the inside of your eye that is sensitive to light.
Neurologic: The doctor will regularly assess your neurological symptoms to quickly identify any related disorders that might come up due to Gardner syndrome.
Treatment Options for Gardner Syndrome
While there isn’t a cure for Gardner syndrome, you can take preventative steps if you know that it runs in your family or if you’ve been diagnosed with the condition. An important part of this is maintaining a healthy diet, given the potential role of diet and environmental factors in triggering the condition.
Nonsteroidal anti-inflammatory drugs (NSAIDs), like sulindac, can also help. They can prevent the growth of polyps in the colon, which is particularly important for people with Gardner syndrome since they’re at a higher risk of developing colon cancer. These medicines can lower this risk with their anti-inflammatory effects.
Regular lower gastrointestinal (GI) endoscopies are strongly recommended. These are procedures that allow doctors to see inside your lower digestive tract and monitor the growth and development of these polyps, as well as catch any that may be turning into cancerous tumors. If you have 30 or more polyps, your doctor may suggest removing your colon. This can significantly reduce your risk of developing colon cancer.
What else can Gardner Syndrome be?
The APC gene mutation is primarily associated with several conditions, namely Gardner syndrome, familial adenomatous polyposis, Turcot syndrome, and other lesser-known forms of familial polyposis. Research shows that these four conditions all share a common mutation on a particular area of chromosome 5.
Gardner syndrome is unique among them due to its specific features, which include polyps in the colon, bone growths known as osteomas, and abnormalities in the retinal epithelium, which is part of the eye. It’s interesting to note that both Gardner syndrome and Turcot syndrome can show up as skin changes. However, they each have a type of skin change that is more common to them. For Gardner syndrome, it’s more common to see skin cysts, while Turcot syndrome is often characterized by spots on the skin that are reminiscent of coffee with milk, known as cafe-au-lait spots.
Surgical Treatment of Gardner Syndrome
If an individual has 30 or more polyps, it may be suggested that removal of the colon might be necessary, to lower the chance of them developing colon cancer. This operation can sometimes include the removal of other parts of the intestines, depending on the specific situation and how much the polyps have grown.
What to expect with Gardner Syndrome
At present, there is no known cure for Gardner syndrome. The outlook for someone with this condition can vary. However, those with a change in the APC gene are very likely to get colon cancer by about the age of 40 if they don’t have surgery and their polyp growth is not controlled.
The best way to manage Gardner syndrome is to monitor the condition and control the symptoms. Regular check-ups are very important. They can help find any concerning changes early. This allows for quick action to be taken, which may greatly improve the outlook.
Possible Complications When Diagnosed with Gardner Syndrome
The main complication of Gardner syndrome is the high chance of developing colon cancer. This can result in serious illness and even death. Many times, mutations in a specific region on chromosome 5 (known as the 5q21 region) are linked to Gardner syndrome. These mutations can often go undetected, as they don’t always cause noticeable issues. However, people with Gardner syndrome are almost certain to develop colorectal cancer at some point.
Colon cancer can start at a younger age than usual in people with Gardner syndrome, and it can result in serious illness or death. This is especially true if the disease is associated with other conditions like fibromatosis or desmoid fibromatosis. Complications from treatment, such as the puncturing of internal body parts, can make the illness worse.
Gardner syndrome can cause other problems outside of the intestines that may get worse over time. This can result in changes in appearance or other noticeable symptoms, leading to a lower quality of life and an increase in serious illness. It is very important to detect Gardner syndrome early and keep a close eye on it. Comprehensive management of the syndrome can help reduce complications and improve overall outcomes for people with this condition.
Complications:
- High chance of developing colon cancer
- Serious illness and potential death
- Younger onset of colorectal cancer
- Fibromatosis or desmoid fibromatosis
- Potential puncturing of internal body parts during treatment
- Lower quality of life
- Increased illness
Early detection, regular monitoring, and comprehensive management are crucial in reducing these risks and improving overall outcomes.
Preventing Gardner Syndrome
Teaching patients about their condition is crucial. This includes understanding what the condition is, how it may affect them, and why it’s essential to take steps to prevent it from getting worse. One of the key things patients need to know is the importance of regular check-ups, such as lower gut examinations. These tests help to keep an eye on any potential growths and can help spot any serious diseases early on. Patients also need to understand that making healthy food choices and taking certain medications, such as NSAIDs, can help manage the condition.
If a patient’s family has a history of Gardner syndrome, genetics counseling is very important. This can help individuals understand their risk of inheriting the condition and make knowledgeable decisions about possible screenings and prevention methods. With a solid understanding of the disease and how to prevent it, patients can take an active role in managing their health. This knowledge empowers them to make informed lifestyle choices and stick to the recommended screening schedules. In the long run, this can improve their overall life quality and outlook for the future.