The clinical presentation of Gardner syndrome varies and often leads to a delay in diagnosis. The extracolonic manifestations may present earlier than gastrointestinal (GI) symptoms, whose detection is critical if appropriate treatment is to be given.

The presence of polyps in the colon may produce signs and symptoms such as rectal bleeding and diarrhea, with exhaustion and fatigue developing due to the associated malnutrition. If obstruction in the GI tract occurs, vomiting, obstipation, peritonitis, and other signs of sepsis may occur. Polyps in other areas of the GI tract may produce different symptoms. Gastric polyps can cause epigastric pain or bleeding, whereas polyps in the duodenum may cause bleeding, pain, or jaundice due to the obstruction of bile flow.

Extracolonic manifestations present in Gardner syndrome lead to a multitude of symptoms [9]. Epidermoid cysts may produce cosmetic defects, and dental abnormalities may cause jaw or teeth pain. Desmoid tumors may cause bleeding or obstruction based on their location. Osteomas, a requirement for the diagnosis of Gardner syndrome, may occur in several locations such as the mandible (most common), skull, paranasal sinuses, or long bones [10].

Epidermoid cysts develop in 50 to 60% of patients with Gardner syndrome and may be present on the scalp, face, or extremities [11]. Majority of patients presents with colonic polyps (villous, tubular, or tubulovillous). Gastric or intestinal polyps may also occur in 12% of patients, as well as periampullary carcinomas in 2% of them [12].

An ocular manifestation commonly associated with Gardner syndrome is congenital hypertrophy of the retinal pigmented epithelium (CHRPE), which are teardrop-shaped lesions located in the midperiphery of the fundus. CHRPE is a sensitive marker for Gardner syndrome, as it has been found to absent in colonic polyposis but is present in some variants of FAP.

In addition, patients with Gardner syndrome are at increased risk for thyroid, adrenal, and liver malignancies.

• Familial Adenomatous Polyposis

  It has been merged into familial adenomatous polyposis (FAP) and is now considered simply a phenotypic variant of FAP. [intelligentdental.com]

  This study was undertaken to determine whether the typical lesions of CHRPE, seen frequently by ophthalmologists, also were indicators of familial adenomatous polyposis. [ncbi.nlm.nih.gov]

  Adenomatous Polyposis Coli Adenomatous Polyposis of the Colon Colon Cancer, Familial Familial Intestinal Polyposis Familial Multiple Polyposis Familial Multiple Polyposis Syndrome Familial Polyposis Coli Familial Polyposis Syndrome FAP Hereditary Polyposis [medicinenet.com]

  Free Books & Documents Excerpt Gardner syndrome is a phenotypic variant of familial adenomatous polyposis. [pubmed.ncbi.nlm.nih.gov]

• Fatigue

  When present, symptoms may include: Blood in the stools Change in bowel habit Fatigue caused by losing blood over time Colorectal polyps should be removed because some can develop into cancer. [nlm.nih.gov]

  The presence of polyps in the colon may produce signs and symptoms such as rectal bleeding and diarrhea, with exhaustion and fatigue developing due to the associated malnutrition. [symptoma.com]

  There may be bleeding from the rectum, diarrhea, fatigue, or epigastric pain. Characteristic findings on physical examination Patients may present with cutaneous and noncutaneous signs and symptoms. [dermatologyadvisor.com]

  […] symptoms of advanced stomach cancer are: nausea and vomiting frequent heartburn loss of appetite, sometimes accompanied by sudden weight loss constant bloating early satiety (feeling full after eating only a small amount) bloody stools jaundice excessive fatigue [healthline.com]

  Case Presentation A 32-year-old woman with a history of depression, fibromyalgia, and CVID treated with monthly intravenous immunoglobulin (IVIG) presented to the emergency department for pleuritic chest pain, fevers, general fatigue, and edema involving [jcadonline.com]

• Fever

  In the case presented, a woman with a clinical history of Gardner syndrome who had previously undergone a total colectomy with ileorectal anastomosis presented to the hospital with a recent history of sore throat, fever, diarrhea, and abdominal pain. [ncbi.nlm.nih.gov]

  ICD 10 J … Wikipedia Hantavirus — A group of viruses that cause hemorrhagic fever and pneumonia. The Hantaviruses include the Hantaan virus that causes Korean (and Manchurian) hemorrhagic fever. [translate.academic.ru]

  Maximum size of ecch ranged from >0 and ≤5 cm (n=26), ≥6 and ≤ 10 cm (n=14), and >10 cm (n=13) and not described in 24 pts Systemic sym at time of ecch, reported in 49 pts, included malaise (n=26), myalgia (n=21), headaches (n=19), fevers (n=15), and [ashpublications.org]

  Contact your doctor if your skin shows any signs of infection such as redness and pain or if you develop a fever. Most infections will go away with antibiotics, but some can be deadly if untreated. [healthline.com]

• Overeating

  It is characterized by the presence of a large number of adenomas in the colonic mucosa (over 100), the size of which varies from small dimensions to 3 cm. [wikilectures.eu]

  Indomethacin therapy over the course of a preceding year was ineffective in one of these patients. One patient (case 4) had diffuse polyposis in an intact colon. [typeset.io]

  There were clinically missing teeth 21 and 23 (no history of extraction revealed) and over-retained tooth 63. Other dental findings were a carious tooth 47. [ncbi.nlm.nih.gov]

  Desmoid tumours associated with Gardner’s syndrome have been shown to have an alteration of the β-catenin pathway and over express β-catenin. Several factors differentiate cutaneous cysts associated with Gardner’s syndrome from ordinary cysts. [intelligentdental.com]

• Abdominal Pain

  We present a case of a 21-year-old patient with polyposis coli and osteoma, which admitted to our hospital with abdominal pain and diarrhea. [scopemed.org]

  Computed tomography (CT) was used to evaluate six patients with Gardner syndrome who, after colectomy, complained either of abdominal pain or of palpable masses. [ncbi.nlm.nih.gov]

  A 75-year-old male patient presented to Al-zahra Clinic with diffuse abdominal pain. An abdominal surgery was performed on him due to invasive abdominal mass. The surgical specimen was examined by H&E and immunohistochemical staining. [ijp.iranpath.org]

• Diarrhea

  We present a case of a 21-year-old patient with polyposis coli and osteoma, which admitted to our hospital with abdominal pain and diarrhea. [scopemed.org]

  In the case presented, a woman with a clinical history of Gardner syndrome who had previously undergone a total colectomy with ileorectal anastomosis presented to the hospital with a recent history of sore throat, fever, diarrhea, and abdominal pain. [ncbi.nlm.nih.gov]

  Unlike most patients with Gardner's syndrome who present with gastrointestinal symptoms such as bloody diarrhea and pain in the abdomen, our patient presented with dental and facial cosmetic issues. [clinicalimagingscience.org]

  Unlike most patients of GS who present with gastrointestinal symptoms such as bloody diarrhea and pain in abdomen, our patient presented with abdominal pain only. [jiaomr.in]

• Abdominal Cramps

  Polyposis The most common presentation of Gardner’s syndrome is nausea, vomiting, mucous, bloody diarrhea, and abdominal cramps or pain. Anemia is also present in many cases. Bowel obstruction is another presentation. [news-medical.net]

  Passage of blood or mucosa, diarrhea, and cramp-like abdominal pain are the common presenting symptoms.[4] The present case also had a complaint of abdominal cramps. [contempclindent.org]

• Blood in Stool

  Non-specific symptoms such as remittent colicky abdominal pain, diarrhea, blood-stained stools, rectal discharge of mucus as well as loss of weight or anemia may occur before a malignant transformation of the polyps [6–9]. [termedia.pl]

  Patients may be asymptomatic or report symptoms such as abdominal pain, change in bowel habit, or blood in stool. [dermnetnz.org]

• Cutaneous Manifestation

  These manifestations are often found to be asymptomatic but may present with pruritus, inflammation, and rupture. Various non-cutaneous manifestations also exist with this syndrome. [pubmed.ncbi.nlm.nih.gov]

  Skin lesions and bone abnormalities often manifest before the development of intestinal polyps. Cutaneous epidermal cysts develop in 35%, osteomas in 80% of patients with GS. [altmeyers.org]

  Treatment Treatment of the cutaneous manifestations of Gardner syndrome depends on the symptomatic or cosmetic nature and the location of the cysts. [dermaamin.com]

• Subcutaneous Nodule

  A 41-year-old woman with painful subcutaneous nodules. N Engl J Med. 2006;355:714-722. Wortham NC, Tomlinson IP. Dercum’s disease. Skinmed. 2005;4:157-62. Steiner J, Schiltz K, Heidenreich F, Weissborn K. [rarediseases.org]

• Irritability

  Seborrheic keratoses are often asymptomatic but can become irritated and inflamed spontaneously or because of chafing from clothing. [aafp.org]

  If they would fix all of those irritants they could easily be a 5 star park!!!! [tripadvisor.ca]

  The ongoing continuous interpersonal stressors had now affected her sleep and appetite, and since a year, she had also become very irritable. She was extremely worried about her future and felt that her situation was hopeless. [ijpm.info]

  Additional symptoms may occur in individuals with Dercum’s disease including fatigue, generalized weakness, a tendency to bruise easily, headaches, irritability, and stiffness after resting, especially in the morning. [rarediseases.org]

• Lethargy

  Her predominant symptoms included sadness of mood, helplessness, hopelessness, feeling of lethargy, and inability to do her routine household work. [ijpm.info]

  In some cases, affected individuals may also experience weight gain, depression, lethargy, and/or confusion. The exact cause of Dercum's disease is unknown. [rarediseases.org]

  On day 9, she developed encephalopathy, with near aphasia, disorientation, and lethargy, which improved rapidly over the next 2 days without further immunosuppressive therapy. [ashpublications.org]

Laboratory evaluation of Gardner syndrome requires several investigations of the organs or organ systems involved in this condition. Peripheral leukocytes are used to evaluate the presence of an APC gene mutation. In addition to imaging studies to detect the presence of extracolonic malignancies such CT scan of the whole abdomen and pelvis and ultrasound of the thyroid gland, complete blood count (CBC), carcinoembryonic antigen testing, and liver function tests may also be requested to detect possible metastasis. Osteomas can be visualized through panoramic dental radiographs, chest X-rays, long bone radiographs, and skull radiographs. Slit-lamp examination and indirect ophthalmoscopy is required to detect CHRPE. Colonoscopy provides direct visualization of the polyps in the colon. Esophagoduodenoscopy (EGD) may be performed to detect the presence of gastric or duodenal polyps.

• Multiple Colonic Polyps

  One child had a subcutaneous fibroma, and another had multiple colonic polyps and exostoses characteristic of Gardner syndrome. Both are autosomal dominant conditions known to predispose to malignancies. [ncbi.nlm.nih.gov]

  Abstract Gardner's syndrome is the association of multiple colonic polyps (familial adenomatous polyposis coli – FAP) with sebaceous cysts and jaw osteomas. [nature.com]

  The colonic polyposis results in multiple colon and intestinal polyps that have a 100 percent chance of becoming malignant, so early intervention is necessary to prolong the life of the patient, explains IJMS. [colgate.com]

  The most common symptom of Gardner syndrome is the development of multiple colon polyps. While the number of polyps can vary from person to person, some individuals develop hundreds of them. [my.clevelandclinic.org]

• Polyps

  Surgical removal of the colon is recommended in patients with multiple advanced polyps. These patients are generally prescribed with a nonsteroidal anti-inflammatory drug (NSAID), to treat remaining polyps. [news-medical.net]

  Polyps in intestinal tract Gardner syndrome, also known as familial colorectal polyposis, is an autosomal dominant form of polyposis characterized by the presence of multiple polyps in the colon together with tumors outside the colon. [intelligentdental.com]

  Clinical and radiological features • Colonic polyps – these are commonly found in intestine. [slideshare.net]

  Panendoscopy did not reveal any pathologies, but 23 small polyps were detected at colonoscopy. Their histopathology provided a diagnosis of adenomatous polyps. [termedia.pl]

  It is characterized by not only the presence of multiple colonic polyposis but also extracolonic ADENOMATOUS POLYPS in the UPPER GASTROINTESTINAL TRACT ; the EYE ; the SKIN ; the SKULL ; and the FACIAL BONES ; as well as malignancy in organs other than [hon.ch]

Gardner syndrome may be treated both surgically and pharmacologically. Surgical treatment is the definitive treatment for the disorder and includes several options:

1. Proctocolectomy with ileostomy [13] [14]
2. Total colectomy with IRA [15] [16]
3. Proctocolectomy with IPAA [17] [18] [19]

Pharmacologic treatments for Gardner’s syndrome include nonsteroidal anti-inflammatory drugs (NSAIDs), which may be given alone or in combination with tamoxifen [20]. Cytotoxic chemotherapy using doxorubicin and dacarbazine may be initiated in order to reduce polyp formation following colectomy and may be used for patients with unresectable disease that does not respond to endocrine therapy, steroids, or NSAIDs [21] [22]. CHRPE does not produce any symptoms and does not require treatment.

The number of polyps is associated with the risk for cancer development in patients with Gardner syndrome. This risk is 2.3 times greater for patients with more than 1,000 polyps compared to those with fewer than 1,000, independent of age [8].

Surgical management is an important factor in survival, as patients older than 45 years old who do not undergo surgical treatment have a 5-year survival rate of 0%. Conversely, the 5-year survival rate for patients who undergo proctocolectomy and mucosectomy with ileal pouch-anal anastomosis (IPAA) is almost 100%. The 20-year recurrence rate with total colectomy is 30%, whereas the recurrence rate at 30 years is 45% after total colectomy with ileorectal anastomosis (IRA).

Long-term control of colorectal tumors is possible with adequate screening. However, the presence of desmoid tumors may significantly affect the survival and quality of life of Gardner syndrome patients.

FAP is a genetic disorder comprising of different disease entities, one of which is Gardner snydrome. The different genetic defects associated with FAP are:

1. Mutation of the APC gene
2. Mutation of the ras gene located on chromosome 12
3. Deletion of the deleted colon cancer (DCC) gene
4. Mutation of the TP53 gene located on chromosome 17
5. DNA methylation defects

In addition, mutations in the MYH gene accompanied by environmental or lifestyle factors such as diet, smoking, and exercise may also play a role in the etiology of Gardner syndrome [3]. However, the most common genetic defect associated with Gardner syndrome is a mutation in the APC gene located in chromosome 5. Although this disease is dominantly inherited, approximately 25% of patients with Gardner syndrome have no family history of the condition [4].

FAP can occur in one individual for every 7,500 births through an autosomal dominant inheritance in approximately 80% of patients, with the remaining 20% representing new or spontaneous mutations. This condition primarily affects the left colon, but the right colon may be the one primarily involved in attenuated FAP.

Gardner syndrome, on the other hand, has a lower incidence than FAP and is present in one individual for every 14,025 live births [5] and has a uniform worldwide distribution [6]. The polyps associated with Gardner syndrome typically develop during adolescence and may undergo malignant progression in the third and fourth decade of life.

The manifestation and severity of Gardner syndrome depends on the point at which the APC gene mutation occurs, usually on the short arm of chromosome 5 (5q21-q22) [7]. There have been more than 1,400 different mutations reported, all of which lead to the development of colonic polyps and to the variability of the extracolonic manifestations seen in Gardner syndrome [7].

Gardner syndrome is a genetic condition and cannot be prevented. However, genetic testing can detect the presence of the gene mutation in susceptible individuals.

The combination of intestinal polyposis and hard and soft tissue tumors [1] such as osteomas, dental abnormalities, epidermoid cysts, and desmoid tumors characterizes a condition known as Gardner syndrome. It is a genetic disease with an autosomal dominant pattern of inheritance, and affected individuals have a 50% chance of passing the condition to their offspring. Gardner syndrome is considered a variant of (familial adenomatous polyposis) FAP and is commonly associated with a mutation in the adenomatous polyposis coli (APC) gene located in chromosome 5 [2].

Untreated intestinal polyps associated with Gardner syndrome demonstrate a high risk for malignant progression. Patients with this disease are also at a higher risk of developing FAP-related malignancies in the liver, bile ducts, pancreas, thyroid gland, adrenal gland, or the central nervous system. No treatment is currently available for Gardner syndrome, though management options may reduce the risk of cancer development.

Gardner syndrome is a rare genetic disorder characterized by the presence of benign (non-cancerous) growths called polyps in the large intestine. It is a variant of a condition known as familial adenomatous polyposis and causes the growth of tumors in other areas of the body such as the skull, jaw, or skin. Gardner syndrome is an inherited genetic condition, and having a parent with this disorder increases your chances of having the same condition. Patients with this syndrome are at a greater risk for developing colon cancer, and treatments for Gardner syndrome are directed towards preventing this outcome. Part of the treatment involves close monitoring of the polyps to ensure that they do not become malignant. The outcome of the disease varies according to the severity of the condition and the effectiveness of the treatment.

1. Oner AY, Pocan S. Gardner's syndrome: a case report. Br Dent J. 2006 Jun 24;200(12):666-7.
2. Payne M, Anderson JA, Cook J. Gardner's syndrome - a case report. Br Dent J. 2002 Oct 12;193(7):383-4.
3. Gu GL, Wang SL, Wei XM, Bai L. Diagnosis and treatment of Gardner syndrome with gastric polyposis: a case report and review of the literature. World J Gastroenterol. 2008 Apr 7;14(13):2121-3.
4. Silva CA, Moraes Pde C, Furuse C, Junqueira JL, Thomaz LA, de Araújo VC. Gardner syndrome with no clinical family history. J Craniofac Surg. 2009 Jul;20(4):1186-9.
5. Lyons LA, Lewis RA, Strong LC, Zuckerbrod S, Ferrell RE. A genetic study of Gardner syndrome and congenital hypertrophy of the retinal pigment epithelium. Am J Hum Genet. 1988 Feb;42(2):290-6.
6. Kamel SG, Kau CH, Wong ME, Kennedy JW, English JD. The role of Cone beam CT in the evaluation and management of a family with Gardner's syndrome. J Craniomaxillofac Surg. 2009 Dec;37(8):461-8. doi: 10.1016/j.jcms.2009.06.007. Epub 2009 Aug 11.
7. Groen EJ, Roos A, Muntinghe FL, Enting RH, de Vries J, Kleibeuker JH, Witjes MJ, Links TP, van Beek AP. Extra-intestinal manifestations of familial adenomatous polyposis. Ann Surg Oncol. 2008 Sep;1(9):2439-50.
8. Debinski HS, Love S, Spigelman AD, et al. Colorectal polyp counts and cancer risk in familial adenomatous polyposis. Gastroenterology. 1996 Apr. 110(4):1028-30.
9. Tulchinsky H, Keidar A, Strul H, et al. Extracolonic manifestations of familial adenomatous polyposis after proctocolectomy. Arch Surg. 2005 Feb. 140(2):159-63; discussion 164.
10. Gorlin RJ, Pindborg JJ, Cohen MM. Syndromes of the Head and Neck. 2nd ed. New York: McGraw-Hill; 1976. pp. 324–8.
11. Ascari-Raccagni A, Baldari U, Righini MG. Cutaneous symptoms of Gardner's syndrome. J Eur Acad Dermatol Venereol. 1999 Jan;12(1):80-1.
12. Fotiadis C, Tsekouras DK, Antonakis P, Sfiniadakis J, Genetzakis M, Zografos GC. Gardner's syndrome: a case report and review of the literature. World J Gastroenterol. 2005 Sep 14;11(34):5408-11.
13. Gu GL, Wang SL, Wei XM, Bai L. Diagnosis and treatment of Gardner syndrome with gastric polyposis: a case report and review of the literature. World J Gastroenterol. 2008 Apr 7;14(13):2121-3.
14. Norwood MG, Mann CD, West K, et al. Restorative proctocolectomy. Does ethnicity affect outcome? Colorectal Dis. 2008 Oct 25.
15. Bess MA, Adson MA, Elveback LR, et al. Rectal cancer following colectomy for polyposis. Arch Surg. 1980 Apr. 115(4):460-7.
16. Almendingen K, Fausa O, Hostmark AT, et al. Serum nutrients and habitual dietary intake in colectomized FAP patients in Norway. Eur J Nutr. 2009 Jan 13.
17. Ambroze WL Jr, Dozois RR, Pemberton JH, et al. Familial adenomatous polyposis: results following ileal pouch-anal anastomosis and ileorectostomy. Dis Colon Rectum. 1992 Jan. 35(1):12-5.
18. Dozois RR, Kelly KA, Welling DR, et al. Ileal pouch-anal anastomosis: comparison of results in familial adenomatous polyposis and chronic ulcerative colitis. Ann Surg. 1989 Sep. 210(3):268-71; discussion 272-3.
19. Kartheuser AH, Parc R, Penna CP, et al. Ileal pouch-anal anastomosis as the first choice operation in patients with familial adenomatous polyposis: a ten-year experience. Surgery. 1996 Jun. 119(6):615-23.
20. Tsukada K, Church JM, Jagelman DG, Fazio VW, McGannon E, George CR, Schroeder T, Lavery I, Oakley J. Noncytotoxic drug therapy for intra-abdominal desmoid tumor in patients with familial adenomatous polyposis. Dis Colon Rectum. 1992 Jan;35(1):29-33.
21. Lynch HT, Fitzgibbons R Jr, Chong S, Cavalieri J, Lynch J, Wallace F, Patel S. Use of doxorubicin and dacarbazine for the management of unresectable intra-abdominal desmoid tumors in Gardner's syndrome. Dis Colon Rectum. 1994 Mar;37(3):260-7.
22. Patel SR, Evans HL, Benjamin RS. Combination chemotherapy in adult desmoid tumors. Cancer. 1993 Dec 1;72(11):3244-7.