AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

In 1859, Charelaigue described the first definitive accounts of adenomatous polyposis in a 16-year-old girl and 21-year-old man.¹ In 1951, Gardner first published an article on familial polyposis, in which he described colonic polyposis in a Utah family whose members had 9 deaths due to colon cancer within 3 generations (average age 34 y). Several genetic disorders may present with GI polyps. Individuals with Gardner syndrome (ie, familial adenomatous polyposis [FAP]) (Online Mendelian Inheritance in Man [OMIM] 175100, 135290) develop adenomatous polyps throughout the GI tract accompanied by extracolonic manifestations, including periampullary adenomas, papillary carcinoma of the thyroid, hepatoblastoma, osteomas of the mandible and skull, epidermal cysts, and desmoid tumors.

Individuals with Turcot syndrome ([OMIM] 276300), a rare autosomal recessive disorder, present with brain tumors (glioblastoma multiforme, medulloblastoma) and colonic adenomas that frequently become malignant in those younger than 30 years. In 1959, Turcot initially described an affected brother and sister whose parents were third cousins.² In 1969, Baughman et al described a family with glioma and polyposis.³

Peutz initially described Peutz-Jeghers syndrome (PJS) in 1921, followed by Jeghers in 1941.^{4, 5} Scattered studies have reported malignant degeneration within GI polyps and development of extraintestinal malignancies, including pancreatic, testicular, and gynecologic malignancies. Development of gynecomastia commonly preceded the development of gynecologic or testicular malignancy. In PJS (OMIM 175200), polyps can occur anywhere within the digestive tract (consistently within the jejunum), accompanied by melanin spots on the lips and digits.

Bannayan-Riley-Ruvalcaba syndrome (BRR), also termed Bannayan-Zonana syndrome, was first described by Riley and Smith in 1961, next described by Bannayan in 1971, and further characterized by Zonana et al in 1975.^{6, 7} In BRR (OMIM 153480), hamartomatous polyps of the colon and tongue are present along with macrocephaly, lipomas, and hemangiomata.

Gorlin and Goltz initially described Gorlin syndrome (GS), also termed nevoid basal cell carcinoma syndrome, in 1960. Herzberg and Wiskemann further associated GS with medulloblastoma in 1963. GS (OMIM 109400) commonly presents with hamartomatous gastric polyps, palmar pits, short metacarpals, odontogenic keratocysts, intracranial calcifications, skeletal malformations, and neoplasia (basal cell carcinoma, ovarian carcinoma, medulloblastoma).

Individuals with Cronkhite-Canada syndrome (average age 62 y) exhibit multiple intestinal polyps and ectoderm abnormalities, including hyperpigmentation of the skin, alopecia, and onychoheterotopia. See Cronkhite-Canada Syndrome.

In 1963, Lloyd and Dennis initially described the features associated with Cowden disease in the family of Rachel Cowden.⁸ In 1972, Weary et al described the manifestations of Cowden disease and classified it as a multiple hamartomatous syndrome with autosomal dominant inheritance.⁹ In 1991, Padberg et al suggested that the disorder known as cerebelloparenchymal disorder VI (Lhermitte-Duclos disease) is part of the multiple hamartoma syndrome.¹⁰ Individuals with Cowden disease present at age 10-30 years with hyperplastic hamartomatous polyps throughout the GI tract (including the esophagus), glycogenic acanthosis of the esophagus, orocutaneous hamartomas of the face, pulmonary hamartomas, and neoplasia (breast, thyroid, adenocarcinoma of the colon [rare]).

Inflammatory polyps are encountered in 1% of young children. Multiple inflammatory polyps throughout the colon that are associated with painless rectal bleeding (rare serious hemorrhage), rectal prolapse, and failure to thrive characterize juvenile polyposis coli. The malignant potential is far less than in Gardner syndrome, with rare scattered reports of adenocarcinoma development.

Pathophysiology

Mutations within the loci of tumor suppressor genes result in the myriad of clinical manifestations of disease. Gardner syndrome (ie, FAP) arises from germline mutations in the adenomatous polyposis coli (APC) gene on band 5q21-22. The APC gene encodes a 2843 amino acid protein involved in cell adhesion and signal transduction. The presentation of Gardner syndrome is related to the site of the APC gene mutation. Proximal APC mutations (proximal to codon 1249) produce a milder Gardner syndrome phenotype with sparse polyposis (<1000 adenomas). APC mutations between codons 1250 and 1330 present with tremendous degrees of polyposis (>5000 adenomas). Local factors may enhance the potential for development of manifestations of Gardner syndrome. Mahmoud et al suggest a role for unconjugated bile acids in the development of periampullary tumors.¹¹

Turcot syndrome is associated with bands 7p22, 5q21-22, and 3p21.3. Several patients with manifestations of Turcot syndrome have documented APC mutations in addition to ocular fundus lesions and jaw lesions consistent with Gardner syndrome; however, patients with Turcot syndrome have a lower degree of colonic polyposis (20-100 total), with malignant transformation by the third decade. Tops et al propose that band 5q21-22 is the nonallelic site to the APC locus.¹² Paraf and colleagues have divided the syndrome into 2 types: brain tumor polyposis type 1 (individuals without Gardner syndrome) and brain tumor polyposis type 2 (individuals with Gardner syndrome).¹³ Studies performed by Paraf and colleagues revealed germline mutations in DNA repair genes (MLH1, MSH2) in patients with brain tumor polyposis type 1.

PJS has been localized via gene linkage and logarithm of odds (LOD) score to band 19p13.3-13.4. Hemminki et al and Jenne et al have reported an abnormal serine-threonine kinase (STK11/LKB1) within this region.^{14, 15}

BRR and Cowden disease have both been mapped to chromosome 10q23.3, which encodes the PTEN gene, a phosphatase functioning within the phosphatidylinositol 3-kinase pathway.

GS is an autosomal dominant mutation localized to band 9q22.3-31, which encodes a human analogue to the Drosophila PTCH gene, a tumor suppressor gene. Advanced paternal age may produce spontaneous GS mutations. 

Current data suggest that Cronkhite-Canada syndrome develops from nongenetic etiologies. See Cronkhite-Canada Syndrome.

Frequency

United States

The Johns Hopkins Hospital Colonic Polyposis Registry, which encompasses 6 states and the District of Columbia, registered 98 Gardner syndrome kindreds and 19 PJS kindreds from 1973-1988.¹⁶ A prevalence of approximately 1:120,000 births is estimated for PJS.

Turcot syndrome is uncommon. In 1997, Paraf et al described a series of 100 patients with manifestations of Turcot syndrome.¹³ Some overlap between kindreds with Gardner syndrome and kindreds with Turcot syndrome may be observed.

BRR is extremely rare and has autosomal dominant inheritance.

Farndon et al have conservatively estimated the prevalence of GS at 1:57,000 population.¹⁷ In individuals who develop basal cell carcinoma when younger than 19 years, the incidence of GS rises markedly to 1:5.

Cowden disease is relatively uncommon. No current estimates of disease prevalence in the United States are available.

International

Gardner syndrome kindreds have been reported worldwide. An increased incidence of APC gene mutation (I1307K mutation) that results in a base transversion in the hypermutable region of the APC gene has been noted in persons of Ashkenazi Jewish descent who have a familial predisposition to colorectal cancer. Burn et al calculated the prevalence of APC mutations in northern England at 2.29 X 10^-5.¹⁸ Bisgaard et al estimated that the incidence of Gardner syndrome among Danish individuals is 1:13,528.

Turcot syndrome (brain tumor, polyposis) is relatively uncommon.

PJS is a rare syndrome with autosomal dominant inheritance in cases described throughout the world.

BRR is also a rare syndrome with probable autosomal dominant inheritance.

The distribution of GS is similar to that in the United States.

Nelen et al have estimated that the prevalence of Cowden disease among Dutch persons is 1:200,000-250,000 population.¹⁹

Mortality/Morbidity

Morbidity and mortality are due to complications from polyps or development of associated malignancies. If untreated, individuals with Gardner syndrome develop adenomatous polyps throughout the colon and rectum, with malignant transformation by age 40 years. Adenomatous polyps can occur in other portions of the GI tract. Periampullary cancer, gastric cancer (especially among Japanese persons), and, rarely, jejunal and ileal carcinomas have been observed. Other malignancies, including desmoid tumors (especially after surgery), hepatoblastoma, adrenal cortical carcinoma, thyroid carcinoma, sarcoma, glioblastoma, and medulloblastoma have been associated with Gardner syndrome.

Morbidity and mortality in Turcot syndrome arises from complications of CNS tumors (medulloblastoma, astrocytoma, gliomas, glioblastoma multiforme, gliomas), GI neoplasia (colonic adenocarcinomas, gastric carcinomas), and basal cell carcinomas of the scalp. Van Meir reported mean survival rates of 5.6 years from diagnosis for patients with medulloblastoma and colonic adenomas and 27.5 months from diagnosis for patients in the subgroup of glioblastoma and adenomas.²⁰

Morbidity and mortality in PJS arises from complications of polyps (eg, intussusception, bleeding, rare malignancy) and development of other malignancies (eg, gynecologic, testicular).

In individuals with BRR, complications from lipomas and arteriovenous malformations, thyroid disease, and an increased incidence of malignancies (eg, thyroid, breast) contribute to morbidity.

White individuals who have GS develop basal cell carcinomas when younger than 20 years. Patients with GS are at increased risk for ovarian carcinoma and medulloblastoma. Children who are younger than 5 years and have medulloblastoma should be tested for GS before initiation of radiation therapy to diminish the risk for early development of basal cell carcinoma.

Morbidity and mortality in Cowden syndrome have arisen from complications of hamartomatous polyps and development of malignancies. Patients with Cowden syndrome have presented with chronic diarrhea and carcinomas of the breast, cerebellum (dysplastic gangliocytoma), thyroid, colon, kidney (renal cell adenocarcinoma), and skin (neuroendocrine [Merkel cell]) carcinoma.

Race

Gardner syndrome, Turcot syndrome, PJS, BRR, and Cowden disease have no race predilection.

Patients who have GS and are of Mediterranean or African descent have diminished risk for developing basal cell carcinomas secondary to skin pigmentation. Kimonis noted that basal cell carcinomas develop in 80% of white patients versus 38% of African American patients.²¹

Sex

The inheritance for Gardner syndrome is autosomal dominant, with nearly 100% penetrance of the APC mutation by age 40 years. Women with Gardner syndrome have an increased risk for the development of thyroid cancer and desmoid tumors. Klemmer et al found an increased incidence of desmoid tumors among females (8% of male vs 13% of females).²² Bell and Mazzaferri reported that 94% of patients with Gardner syndrome who had thyroid carcinoma were women.²³

The inheritance of Turcot syndrome is autosomal recessive. No differences in symptom manifestations between the sexes has been reported.

The inheritance for PJS is autosomal dominant. The life expectancy for women with PJS may be decreased by development of gynecologic malignancies. Males with PJS are at increased risk for development of testicular cancer.

In BRR, 80% of the reported cases have appeared in males.

GS is considered to be autosomal dominant. Approximately 40% of cases are new mutations.

Age

Patients with Gardner syndrome generally present in late adolescence with symptoms of polyposis (GI bleeding). Some patients with Gardner syndrome have reported GI bleeding in early childhood. Children with Gardner syndrome can present with extraintestinal manifestations before symptoms of polyposis arise, including medulloblastoma, hepatoblastoma, osteomas, or retinal pigment epithelium hypertrophy.

School-aged children have presented with Turcot syndrome and gene mutations related to Gardner syndrome (mean age 15.3 y, range 5-38 y) with medulloblastoma and colonic adenomas. Patients in the non–Gardner syndrome subgroup develop glioblastomas, and colonic adenomas develop somewhat later (mean age 18 y; range 4-70 y).

Children with PJS have presented in the neonatal period with complications of GI polyposis.

Children with BRR often exhibit high birthweight and length, hypotonia and diminished coordination, and mild mental retardation.

Neonates with GS present with lung cysts, rib and vertebral anomalies, palmar pits, hydrocephalus, and cleft palate. Symptoms of medulloblastoma in GS manifest in patients younger than 2 years. Basal cell carcinomas generally appear in patients with GS who are aged in their early twenties but may present in patients younger than 10 years.

Patients with Cowden syndrome may present during early childhood with craniomegaly, mild or moderate developmental delay, and scrotal tongue. During later childhood, trichilemmomas within the nasolabial folds, palmar pits, subcutaneous lipomas, and hemangiomas manifest. Symptoms from polyposis have resulted in colectomy during adolescence and have been reported in patients aged 18 months. Adults with Cowden disease have an increased incidence of breast cancer (30%), nonmedullary thyroid cancer, adrenal carcinoma, skin carcinoma, and dysplastic gangliocytomas.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Manifestations of adenomatous polyposis can affect the entire body. Talbot classifies the manifestations of Gardner syndrome via tissue distribution.²⁵
• • In most individuals, symptoms of polyposis manifest as sessile tubular adenomas in late adolescence; however, some individuals have developed polyps in early childhood.
  • Fundic gland polyps rarely develop into gastric cancer.
  • Mesodermal sites associated with Gardner syndrome include fibrous tissue (desmoid tumors), bone (osteomas, dental anomalies), and liver (hepatoblastoma).
  • Ectodermal tissues include the eyes (congenital hypertrophy of the retinal pigment), skin (cysts), CNS (medulloblastoma), and endocrine system (thyroid carcinoma, multiple endocrine neoplasia 2B).
• Van Meir classified the presentation of patients with Turcot syndrome into 2 categories, stratified by the presence or absence of colorectal phenotype.²⁰ Patients with medulloblastoma who expressed the colorectal phenotype were older than 17 years at disease onset, whereas patients with medulloblastoma in the absence of the colorectal phenotype were younger than 10 years at disease onset. Hamilton et al reported that several patients with Turcot syndrome have mutations in the APC gene.²⁶ These patients also have manifested ocular fundus lesions, epidermal inclusion cysts, and osteosclerotic jaw lesions consistent with Gardner syndrome. 
• Patients with PJS generally present with the following symptoms:
• • GI bleeding 
  • Intussusception 
  • Rectal prolapse
  • Nasal polyposis (chronic sinusitis)
  • Pigmented macules
  • Gynecomastia (The development of gynecomastia in a child with suspected PJS should prompt investigation for underlying testicular or gynecologic malignancy.)
• Features commonly associated with BRR (ie, Bannayan-Zonana syndrome) include high weight and length at birth. Growth velocity generally tapers by the time the patient is aged 7 years.
• • Children often present with developmental delay, mild mental retardation, and hypotonia. Parents commonly report excessive drooling.
  • Cutaneous features frequently include lipomas (70% of patients), myopathy (60% of patients), hamartomatous GI polyps (45% of patients), hemangiomata (10% of patients), and telangiectasias. Typical dermatologic findings include vascular malformations, lipomatosis, speckled lentiginosis of the penis or vulva, facial verrucae–like or acanthosis nigricans–like lesions, and multiple acrochordons of the neck, axilla, and groin.
  • Other reported features include testicular enlargement, cryptorchidism, Hashimoto thyroiditis, and congenital heart disease (ventricular septal defect).
  • Gut malrotation has been documented in a patient.
• Patients with GS may present in infancy with congenital hydrocephalus, cleft lip and palate, lung cysts, rib and vertebral anomalies, and palmar pits. A case report by Genevieve et al described a child with GS who presented prenatally with a chylothorax.²⁷ Enamel hypoplasia has also been described in the dental literature and attributed to lyonization.
• • Children at risk for inheritance of the gene should undergo a detailed examination at birth to look for palmar pits and other physical features, as well as radiologic evaluation of the rib, skull, and spine. 
  • Children with GS may present with symptoms of medulloblastoma when younger than 5 years.
  • Dental anomalies and basal cell carcinoma can appear in adolescents.
• Cowden disease is less common in children than in adults, but patients may present with the following features:
• • Developmental delay
  • Macrocephaly (38%)
  • Cerebellar dysfunction
  • Scoliosis
  • Cutaneous hamartomas
  • Thyroid disease (>50%)
  • Chronic diarrhea
  • Malignancies
  • • Neoplasia of the breast develops in 75% of females with Cowden disease.
    • Other malignancies that have been reported in patients with Cowden disease include dysplastic gangliocytomas of the cerebellum, ovarian tumors, thyroid tumors, renal cell adenocarcinoma, and Merkel cell carcinomas
  • Visceral arteriovenous malformations
  • • These malformations have been reported in a family diagnosed with Cowden syndrome and, based on genetic testing findings, were found to have a frameshift mutation in the PTEN gene.
    • This association has been attributed to hypothesized function of the PTEN gene in the suppression of angiogenesis.

Physical

• Physical features commonly associated with Gardner syndrome include the following:
• • Skin - Epidermal cysts (commonly on the back), sebaceous cysts (commonly on the back)
  • Craniofacial - Osteomas (including the mandible), skin fibromas, dental anomalies (supernumerary teeth, impacted teeth, missing teeth, root anomalies)
  • Ocular - Congenital hypertrophy of the retinal pigment epithelium
  • GI - Multiple gastric polyps, multiple duodenal polyps, multiple colonic polyps, mesenteric fibromas (desmoids)
  • Endocrine - Cushing syndrome (adrenal carcinoma), multiple endocrine neoplasia 2B
  • Oncology - Malignant transformation of polyps, gastric carcinoma, periampullary carcinoma, hepatoblastoma, biliary ductal carcinoma, osteosarcoma, adrenal carcinoma (Cushing syndrome), thyroid carcinoma
• Attributes of Turcot syndrome include the following:
• • Skin - Café au lait spots, multiple lipomas, basal cell carcinoma of the scalp
  • GI - Colonic polyps (including adenomatous), hepatic focal nodular
    hyperplasia, adenocarcinoma of the colon, gastric carcinoma
  • CNS - Glioma, glioblastoma multiforme, astrocytoma
• The following findings are common in PJS:
• • Skin - Melanin spots on the lips, digits, and oral mucosa
  • GI - Multiple GI polyps (especially jejunal), intussusception, GI bleeding, rectal prolapse
  • Genitourinary (GU) - Polyps within ureter, bladder, and renal pelvis
  • Pulmonary - Nasal and bronchial polyps
  • Thorax - Gynecomastia (testis, ovarian tumors)
• Common findings associated with BRR (ie, Bannayan-Zonana syndrome) include the following:
• • General - High weight and length at birth, macrocephaly, scaphocephaly, broad thumb and hallux
  • CNS - Hypotonia and myopathy, developmental delay, mild mental retardation
  • Cardiovascular - Arteriovenous malformation, congenital heart disease (eg, ventricular septal defect)
  • Pulmonary - Pectus excavatum
  • GI - High palate, hamartomatous intestinal polyps (colon, tongue)
  • GU - Enlarged penis, spotted pigment of glans penis, testicular enlargement
  • Ocular - Pseudopapilledema, exotropia
• Physical characteristics associated with GS include the following:
   
• • Skin - Basal cell nevi and carcinoma
  • Craniofacial - Broad facies, including nasal root, bossing of frontal and parietal bones, cleft lip and palate, mandibular prognathism, dental anomalies (odontogenic keratocysts)
  • Ocular - Strabismus, hypertelorism, colobomas, subconjunctival epithelial cysts, glaucoma
  • Cardiac - Cardiac fibromas
  • Pulmonary - Congenital lung cyst, rib anomalies
  • GI - Hamartomatous gastric polyps, lymphomesenteric cysts
  • GU - Ovarian fibromas and carcinomas
  • CNS - Congenital hydrocephalus, mental retardation, medulloblastoma 
  • Skeletal - Scoliosis, kyphoscoliosis, cervical anomalies, rib anomalies, brachydactyly, short fourth metacarpal and thumb
• Manifestations of Cowden disease include the following:
• • Skin - Multiple hamartomas of skin and mucus membranes, verrucous lesions, papules of gingival and buccal mucosa, facial trichilemmomas 
  • Cerebrospinal, head - Craniomegaly, adenoid facies, ataxia, increased intracranial pressure, cerebellar degeneration, mental retardation, tremors, tonsillar herniation, seizures
  • Endocrine - Thyroid hamartomas and carcinoma 
  • Chest - Breast hamartomas and carcinomas, pectus excavatum 
  • GI - Scrotal tongue, intestinal polyps (hamartomatous)
  • Oncology - Dysplastic cerebellar gangliocytoma, breast carcinoma, ovarian carcinomas, Merkel cell skin carcinomas, renal cell adenocarcinomas, thyroid carcinomas
  • Spine - Scoliosis

Causes

• Gardner syndrome arises from mutations within the APC gene.
• • The APC protein contains several functional regions that serve as binding and turnover loci for beta-catenin. Beta-catenin structures tissue architecture and activates E-cadherin, which regulates adherens junctions between epithelial cells.
  • Based on experimental data within a Drosophila model, Peifer hypothesized that the APC complex governs the signaling of contact inhibition within the cell. ²⁸
  • Most mutations within the APC gene occur within the central area (mutation cluster region) and generate truncated APC proteins.
  • Mutations situated within either the first or last third of the APC gene result in a late-onset attenuated polyposis phenotype; however, central region APC mutations exhibit a severe phenotype with vast numbers of polyps occurring early in life and extracolonic manifestations.
• The cause for PJS appears to be multifactorial.
• • Abnormalities in the STK11 gene, a serine-threonine kinase and tumor suppressor gene involved in the development of hamartomas, may facilitate the development of carcinomas. 
  • Additional mutation events may also be necessary for the development of PJS.
• BRR (ie, Bannayan-Zonana) syndrome has been localized to band 10q23.3, the same region in which Cowden disease is located.
• • Further studies have localized the PTEN gene, a tumor suppressor, to this area.
  • The phosphatase encoded by the PTEN gene functions within the phosphatidylinositol-3-kinase pathway.
  • Loss of gene function predisposes to future development of neoplasia.
• GS has been mapped to band 9q22.3-q31.
• • Studies by Hahn et al, Johnson et al, and Bale have explored similarities in GS to the Drosophila PTCH gene that is expressed in the sclerotome, branchial arch, limb, skin, and spinal cord.^{29, 30, 31}
  • Bale noted that phenotypic expression of GS varied more among families, suggesting the importance of neighboring genes in modulation of phenotypic expression.³¹
• Nelen et al confirmed that the PTEN gene is the locus for Cowden disease.¹⁹
• • The PTEN gene has been localized to band 10q22-23 and modulates the phosphoinositide-3-kinase signaling pathway via phosphorylation of phosphoinositides to regulate cell growth and survival. 
  • Arch et al noted overlap in features of BRR and Cowden syndrome, both of which are associated with PTEN mutations.³²

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Vascular lesions of the gut (eg, blue rubber bleb nevus)
Hereditary nonpolyposis colon cancer
Intussusception
Rectal prolapse
Cowden syndrome
Gastrointestinal bleeding

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• CBC count with differential and platelets 
• Stools for occult blood
• Prothrombin time/activated partial thromboplastin time (if significant bleeding is present) 
• Serum albumin levels (if weight loss is present) 
• Genetic testing
• • Band 5q21-22 for Gardner syndrome (ie, FAP)
  • Band 7p22, 5q21-22, and 3p21.3 for Turcot syndrome
  • Band 19q13.3-13.4 for PJS
  • Band 10q23.3 for BRR and Cowden disease
  • Band 9q22.3-q31 for GS
• Fecal alpha1-antitrypsin or fecal calprotectin (if albumin is low and weight loss is present; to evaluate for protein-losing enteropathy)
• Levothyroxine (T4), triiodothyronine (T3), thyroid-stimulating hormone (TSH), thyroid antimicrosomal or thyroid peroxidase antibody to exclude Hashimoto thyroiditis in individuals with symptomatic BRR
• Liver function tests and alpha-fetoprotein level to screen for hepatoblastoma in patients with suspected Gardner syndrome and an abdominal mass; electrolytes, plasma or urine cortisol, and adrenocorticotropic hormone (ACTH) in patients with suspected Gardner syndrome if Cushing syndrome is present

Imaging Studies

• Upper GI with small bowel followthrough (SBFT) is used to evaluate for polyps. 
• Air-contrast barium enema (BE) is used to evaluate for colonic polyps.
• Additional imaging studies in patients with Gardner syndrome may include the following: 
• • Radiographs of the skull, teeth, and mandible to screen for osteomas and plan management of dental anomalies
  • Endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP) to evaluate biliary tree for polyps and carcinoma, if clinical suspicion warrants 
  • CT scanning, ultrasonography, or MRI of the abdomen to evaluate abdominal masses (hepatoblastoma, adrenal carcinoma, mesenteric fibromas/desmoids)
• In patients with Turcot syndrome, CNS imaging, GI imaging, and other imaging modalities are indicated if Gardner syndrome is suspected, as clinically warranted.
• Imaging studies in patients with PJS include the following:
• • Perform routine screening, mammogram, and breast ultrasound for early detection of occult neoplasms.
  • Perform ultrasonography or CT scanning of the pelvis or testicles to screen for possible malignancies in patients with conditions such as gynecomastia and precocious puberty.
• Imaging studies in patients with BRR include the following:
• • In patients with PTEN mutations, routine surveillance for occult breast neoplasms is warranted.
  • Perform CNS imaging to exclude occult malignancy, if clinical suspicion warrants.
• Imaging studies in patients with GS include the following:
• • Perform radiography of the mandible, ribs, and spine to diagnose and treat anomalies.
  • Perform CNS imaging to exclude hydrocephalus and medulloblastoma if warranted by clinical evaluation.
  • Perform imaging of the ovaries to exclude pathologic conditions of the ovaries in women with suggestive symptoms.
  • Patients with GS should not require SBFT or BE for detection of polyps (only gastric polyps have been reported).
  • In a series of 105 patients with GS, Kimonis et al reported the following radiologic findings:²¹
  • • Calcification of the falx cerebri (65%)
    • Bridged sella (68%)
    • Flame-shaped lucencies in the phalanges, carpals, and metacarpals (30%)
    • Bifid ribs (26%)
    • Calcification of the tentorium cerebri (20%)
    • Hemivertebrae (15%)
    • Fused vertebral bodies (10%)
  • In patients with Cowden disease, perform the following:  
  • Routine breast imaging to screen for neoplasia (Seventy-five percent of females develop breast neoplasia.)
  • Imaging of the thyroid, if suggestive of malignancy
  • Imaging of the ovaries, if suggestive of malignancy
  • MRI of the head, if symptomatic
  • Radiography of the spine to monitor for scoliosis

Other Tests

• All patients with polyposis syndromes require serial endoscopy to evaluate for the degree of polyposis and survey for malignant transformation. Patients with congenital heart disease, vascular grafts, or valvular replacements may require subacute bacterial endocarditis (SBE) prophylaxis.

Procedures

• Perform upper endoscopy or colonoscopy to evaluate GI polyposis and perform surveillance for malignant transformation. Patients with congenital heart disease may require SBE prophylaxis.
• In patients who have PJS and chronic sinusitis, endoscopic evaluation for possible nasal polyposis may be required. Squamous cell carcinoma has been reported in a patient with PJS and nasal polyps.
• In patients with GS, skin biopsies may be required to exclude basal cell carcinomas.
• In patients with Cowden disease, biopsies of suspicious lesions that show on the mammogram are warranted to exclude neoplasia, and biopsies of other suspicious areas are indicated to exclude malignancy.

Histologic Findings

Gruber et al characterized PJS hamartomas with an elongated frondlike epithelium possessing cystic dilatation of glands containing hypermucinous goblet cells atop a network of smooth muscle bundles.³³ Patients with BRR and Cowden disease also present with hamartomatous intestinal polyps. In contrast, other forms of juvenile polyposis consist of abundant lamina propria without the presence of smooth muscle bundles. Inflammatory polyps contain a well-differentiated mature epithelial layer with a smooth dome but lobulated appearance due to cyst formation without smooth muscle bundles.

Adenomatous polyps, found in patients with Gardner syndrome and Turcot syndrome, vary in size, ranging from single crypt adenomas to microadenomas of 2-5 crypts in size to sessile tubular adenomas visualized at endoscopy. Adenomas are composed of immature epithelial cells with increased proliferation rates above crypt requirements. Increased growth in size of adenomas enhances the formation of dysplasia. No smooth muscle bundles are present in adenomatous polyps.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Gardner syndrome
• • Patients require medical care and management of cutaneous cysts, osteomas, fibromas, polyposis, and diligent surveillance for neoplasia.
  • Carcinoma may develop at any age, from late childhood through senior years.
  • Young children with gene mutations related to Gardner syndrome have an increased risk for development of hepatoblastoma. Hughes and Michels noted Gardner syndrome in 2 of 470 children who had parents with Gardner syndrome versus an incidence of 1 per 100,000 general population.³⁴
  • Patients with Gardner syndrome are predisposed to the development of polyposis throughout the GI tract and to carcinomas of the stomach, periampullary region, biliary tract, and colon.
  • Women with Gardner syndrome have an increased risk of desmoid tumors and thyroid carcinoma.
  • Development of thyroid carcinoma is 100 times more likely among patients with Gardner syndrome.
  • Osteosarcomas and adrenal carcinomas (with Cushing syndrome) have been previously reported in patients with Gardner syndrome.
• Turcot syndrome
• • Patients require medical intervention for complications of GI polyposis and carcinoma (eg, gastric, colonic), management of basal cell carcinomas, and treatment of CNS malignancies, including astrocytoma, glioblastoma, and medulloblastoma.
  • Patients with Turcot syndrome are predisposed to the development of hepatic focal nodular hyperplasia.
• PJS
   
• • Patients require medical management for problems attributed to polyposis and for detection of malignancy.
    
  • Patients with PJS may develop significant GI bleeding, intussusception, and rectal prolapse requiring diagnosis and treatment, including endoscopy and surgical resection. 
  • Nasal endoscopy may be necessary in the presence of chronic sinusitis to exclude the presence of significant nasal polyps. 
  • Long-term surveillance strategies to monitor for GI malignancies, including bowel, pancreatic, and extraintestinal malignancies (eg, breast, gynecologic, testicular), are currently under development at several centers.
  • The use of the potassium titanyl phosphate (KTP) laser to treat mucocutaneous melanosis of the lips and hands in a patient with PJS has been reported in the United Kingdom.
• BRR syndrome
• • Patients require medical therapy for CNS abnormalities, complications of lipomas and arteriovenous malformations, treatment of Hashimoto thyroiditis, and surveillance for malignancy.
  • Children with BRR exhibit hypotonia, developmental delay, and mild mental retardation requiring coordinated speech and occupational and physical therapies to maximize potential.
  • Significant lipomatous or vascular lesions (hemangiomas, arteriovenous malformations) have resulted in CNS complications (eg, seizures), amputations, and premature death.
  • Patients with BRR appear to have an increased risk for CNS tumors.
  • Increased incidences of Hashimoto thyroiditis, along with abnormalities of the PTEN gene (tumor suppressor gene), enhance the likelihood for development of neoplasia, especially thyroid and breast.
• GS
• • Patients may require medical attention for craniofacial, vertebral, dental, and ophthalmologic abnormalities, in addition to diagnosis and treatment of potential neoplasia.
  • Bale reported that 3% of patients with GS presented with cleft lip and palate at birth.³¹
  • Scoliosis is commonly associated with GS. 
  • Jaw cysts are noted in more than 50% of patients, accompanied by symptoms of optic nerve compression, abnormalities of taste, and facial paresthesias.
  • Fibrosarcomas of the jaw have been encountered in patients with GS.
  • Glaucoma and cataracts have been described in patients with GS.
  • Patients with GS are predisposed to the development of neoplasia of the CNS, skin, and reproductive organs. 
  • In childhood, medulloblastomas have been reported in 5% of patients with GS.
  • Basal cell carcinomas may present in patients younger than 10 years, especially with prior history of exposure to ionizing radiation. Nearly all patients with GS develop basal cell carcinomas by the fourth decade of life.
  • Individuals with GS may present with abdominal symptoms that arise from abnormalities of the GI (lymphatic, mesenteric cysts) and gynecologic systems. Young girls with GS may develop ovarian fibromas (predisposed to torsion) and fibrosarcomas. Khalifa et al reported endometrial adenocarcinoma in a 37-year-old woman with GS.
• Cowden disease
• • Patients require medical attention for management of complications of hamartomatous polyps, thyroid disease, scoliosis, and CNS abnormalities (eg, seizures, increased intracranial pressure).
  • Patients require careful monitoring for the development of malignancies within the cerebellum, breast, skin (Merkel cell), and kidneys (renal cell adenocarcinoma).

Surgical Care

• Patients with Gardner syndrome require surgical treatment of the following:
• • Cutaneous cysts
  • Symptomatic dental anomalies and osteomas
  • Biopsy and resection for malignancies, including hepatoblastoma, colonic carcinoma, thyroid carcinoma, osteocarcinoma, gastric carcinoma, periampullary carcinoma, and biliary tract carcinoma
  • Liver transplantation (may be required in patients with hepatoblastoma)
• Patients with Turcot syndrome require surgical intervention for diagnosis and management of CNS lesions, gastric lesions, colonic polyposis, and hepatic lesions.
• PJS
• • Patients may require surgical intervention for symptomatic GI lesions and biopsy of suspicious areas to exclude the possibility of malignancy.
  • Some patients with PJS develop manifestations of short-bowel syndrome secondary to long-term resections.
• Patients with BRR may require surgical intervention for management of serious lipomatous, vascular lesions, and undescended testicles and biopsy of suggestive areas to exclude the possibility of occult malignancy.
• Patients with GS may require surgical management for the following:
• • Craniofacial lesions (cleft lip and palate, jaw cysts, other mandibular lesions)
  • Abdominal masses (mesenteric cysts, lymphatic cysts, ovarian fibromas)
  • Diagnostic and therapeutic interventions for potential neoplasia within the CNS (medulloblastoma), skin (basal cell carcinoma), jaw (fibrosarcoma), ovaries (fibrosarcoma), and endometrium (adenocarcinoma)
• Patients with Cowden disease require surgical intervention for management of symptomatic polyposis, scoliosis, and increased intracranial pressure.
• • Biopsy and resection of lesions within the cerebellum (dysplastic gangliocytomas), breast, and kidneys (renal cell adenocarcinoma) may be required.
  • Consideration of prophylactic mastectomy is recommended for women with Cowden disease.

Consultations

• Patients with Gardner syndrome may require consultation with the following:
• • Gastroenterologist - For monitoring and surveillance for malignancies
  • Oncologist - For treatment of malignancies
  • Surgeon - For biopsy or resection of suspicious areas
  • Dentist or maxillofacial surgeon - For mandibular osteomas or dental anomalies
  • Ophthalmologist - For evaluation for retinal anomalies
  • Endocrinologist - For evaluation and management of thyroid carcinoma and adrenal carcinoma
• Patients with Turcot syndrome may require medical consultation with the following:
• • Gastroenterologist - For monitoring and surveillance for malignancies
  • Oncologist - For monitoring and treatment of malignancies
  • Dermatologist
  • Surgeon - For management of CNS, cutaneous, and GI malignancies
• Patients with PJS may require consultation with the following:
   
• • Gastroenterologist: Assistance from a gastroenterologist may localize sites of polyps or bleeding.
  • Surgeon: Surgical intervention may include resection of symptomatic areas and biopsy for suspicious malignancy.
  • Dermatologist: Some patients with PJS may initially present to the dermatologist for diagnosis of cutaneous lesions.
  • Endocrinologist
  • Gynecologist
  • Urologist
  • Otolaryngologist
  • Oncologist: An oncologist directs appropriate therapy in the presence of intestinal or extraintestinal malignancy.
• Patients with BRR may require consultation with the following:
• • Dermatologist
  • Developmental pediatrician: The developmental pediatrician manages seizures and develops strategies for neurodevelopmental stimulation.
  • Endocrinologist: An endocrinologist treats Hashimoto thyroiditis and cryptorchidism.
  • Gastroenterologist: A gastroenterologist evaluates for polyposis, manages symptoms of drooling, and establishes GI surveillance. 
  • Gynecologist: A gynecologist establishes surveillance strategies for breast neoplasia.
  • Neurologist: The neurologist manages seizures and develops strategies for neurodevelopmental stimulation.
  • Oncologist: An oncologist directs appropriate therapy if malignant transformation occurs.
• Patients with GS may require subspecialty support for treatment of craniofacial and ophthalmologic abnormalities, management of scoliosis, and surveillance and treatment of potential neoplasias (eg, medulloblastoma, basal cell carcinoma, ovarian fibromas and sarcomas, mesenteric cysts).
• Patients with Cowden disease may benefit from the following consultations:
• • Neurologist - For seizures and tremors
  • Endocrinologist - For thyroid
  • Gastroenterologist - For hamartomatous polyps
  • Oncologist - For management and treatment of potential malignancies
  • Surgeon - For treatment of increased intracranial pressure, cerebellar lesions, breast cancer, thyroid lesions, and renal carcinoma

Diet

• The benefits of low-fat/high-fiber diets and supplementation with either calcium or antioxidants, including ascorbic acid and alpha-tocopherol, is controversial in patients with Gardner syndrome. Several controlled trials in adults have studied dietary interventions, including wheat bran on the rate of development of adenomatous polyps.
• • In a 4-year Gardner syndrome trial, patients were randomized to either 4 g of ascorbic acid plus 400 mg of alpha-tocopherol alone or 22.5 g of daily fiber supplement.
  • Based on actual intake, the combined intervention diminished the rate of formation of rectal polyps.
  • The Australian polyp prevention trial noted a reduced incidence of adenoma formation with reduced fat and increased bran intake.
  • Yang et al noted a decrease in colonic epithelial proliferation activity via increasing calcium intake to 1200 mg with low-fat dairy foods; however, the Toronto polyp prevention trial found no difference in the incidence of polyp recurrence between a low-fat/high-fiber diet and a typical Western diet with placebo fiber.
  • Fuchs et al also noted no protective effect of dietary fiber against colorectal adenomas and carcinoma in women.³⁵
• No studies are currently available regarding dietary modification in patients with PJS. Development of short-bowel syndrome from repetitive intestinal resections requires special nutritional interventions, including vitamin and nutrient supplementation, continuous enteral feedings, or parenteral nutrition.
• No studies are currently available regarding dietary modification in patients with BRR, Cowden disease, or GS.

Activity

• No limitation of activity is mandated for patients with PJS, BRR, Gardner syndrome, or Turcot syndrome unless other medical issues necessitate restrictions.
• Patients with GS should minimize exposure to ultraviolet light and ionizing radiation to reduce the risk of developing basal cell carcinomas.
• No limitation of physical activity is mandated for patients with Cowden disease unless other physical conditions are present. Patients with Cowden disease have an increased risk for development of thyroid carcinoma and may wish to minimize exposure of the neck to ionizing radiation.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, have been consistently associated with diminished risk of colorectal cancer. Sulindac has been reported to cause regression of adenomas in patients with Gardner syndrome. NSAIDs suppress cyclooxygenase-2 (COX-2), which affects epithelial proliferation and apoptosis.

Studies by Watanabe et al suggest an important role of antagonistic agents for the prostaglandin EP1 receptor for chemoprotection against the development of colon cancer.³⁶

Drug Category: Nonsteroidal anti-inflammatory drugs (NSAIDs)

These agents have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action inhibits cyclooxygenase activity and prostaglandin synthesis. Other mechanisms, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions, may also occur.

Drug Category: Cyclooxygenase-2 (COX-2) inhibitors

These agents inhibit COX-2, thus suppress production of prostaglandin E2 at inflammation sites.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Patients with Gardner syndrome may require inpatient management for evaluation and treatment of suspicious lesions.
• Patients with Turcot syndrome may require inpatient management for evaluation and treatment of potential malignancies within the CNS and GI tract.
• Patients with PJS may require inpatient treatment of intussusception, significant GI bleeding, and evaluation for malignancy. Both invasive and noninvasive evaluations may be indicated, including endoscopy, biopsy, and resection for diagnosis, with treatment of associated medical issues (eg, anemia) as dictated by the clinical scenario.
• Patients with BRR may require inpatient treatment of clinically significant lipomatous and vascular lesions resulting in compromised organ function or circulatory compromise. Patients with BRR may also require treatment of seizures and evaluation for suspected malignancy.
• Patients with GS may need inpatient assessment of symptomatic cardiac fibromas, surgical correction of palatal abnormalities and scoliosis, and treatment of neoplasia.
• Patients with Cowden disease may require inpatient treatment of CNS abnormalities and surgical treatment of malignancies.

Further Outpatient Care

• Outpatient treatment for the patient with Gardner syndrome includes treatment of cutaneous cysts; symptomatic osteomas (eg, mandibular); dental anomalies; and diligent surveillance for neoplasia within the GI tract, liver (hepatoblastoma), thyroid, bone, and adrenal glands.
• Outpatient treatment for the patient with Turcot syndrome includes surveillance for malignancy and treatment of complications within the GI tract, skin, and CNS.
• Outpatient treatment for the patient with PJS includes monitoring for complications of GI polyposis, surveillance for underlying malignancies, and treatment of complications of disease, including short-bowel syndrome secondary to multiple bowel resection.
• Outpatient treatment for the patient with BRR includes therapies for neurologic and developmental issues, management of thyroid disease, and surveillance and treatment of underlying malignancies.
• Outpatient treatment for the patient with GS includes evaluation and treatment of ophthalmologic abnormalities (eg, strabismus, glaucoma), cleft lip and palate, odontogenic cysts, scoliosis, and cardiac fibromas. Patients with GS require lifetime surveillance for malignancies, including basal cell carcinoma (adolescence, adulthood), ovarian and uterine carcinoma, medulloblastoma and astrocytoma (early childhood), lymphatic and mesenteric cysts, and sarcomas.
• Outpatient treatment for the patient with Cowden disease includes management of thyroid disease, scoliosis, and CNS abnormalities. Patients with Cowden disease have a predisposition for development of cerebellar, breast, skin (Merkel cell), and renal malignancies.

Transfer

• Patients with polyposis may require transfer for diagnosis and treatment if appropriate support is not available.

Deterrence/Prevention

• Patients with Gardner syndrome require routine surveillance for GI malignancy via guaiac cards in the asymptomatic patient and serial upper and lower endoscopies and small bowel evaluation.
• Patients with Turcot syndrome require surveillance for malignant transformation within gastric and colonic polyps, cutaneous surveillance for basal cell carcinomas, and possible CNS malignancies.
• PJS
• • In patients with PJS, establishment of surveillance programs for occult malignancies may permit early detection.
  • The development of gynecomastia of precocious puberty in a child with PJS merits further diagnostic investigation to exclude underlying testicular or gynecologic malignancy.
• In patients with BRR, establishment of breast self-examination programs and routine mammography may allow early detection of pathologic conditions of the breast; however, 80% of patients are male.
• GS
• • Patients with GS should minimize exposure to ultraviolet light and ionizing radiation to deter the development of basal cell carcinomas.
  • Establishment of skin self-examination programs may facilitate early detection of basal cell carcinomas.
  • Patients with GS should have ophthalmologic screening for glaucoma and cataracts.
  • Patients should have routine dental follow-up care if cysts are present within the jaw.
  • Women should undergo routine gynecologic examinations.
• Cowden disease
• • Patients with Cowden disease have an increased risk for development of breast cancer. Early institution of screening programs and consideration of prophylactic mastectomy should be considered.
  • In addition, patients with Cowden disease are predisposed to the development of thyroid disease; complications from hamartomatous GI polyps; and cerebellar, skin, and renal malignancies.

Complications

• Patients with Gardner syndrome may experience complications from malignancies and from benign lesions, such as mandibular osteomas or dental anomalies.
• Patients with Turcot syndrome may experience complications from malignancies.
• PJS
• • Patients may develop medical and surgical complications from GI polyps and malignancies. Some reports suggest that approximately one fourth of patients require laparotomy for small bowel intussusception by age 10 years.³⁷
  • Repeated intestinal resections may result in short-bowel syndrome with total parenteral nutrition (TPN) dependence.
  • Patients with PJS have an increased risk for the development of malignancies within the GI tract, pancreas, breast, uterus, and testicles.
  • Complications from GI polyps and malignancies may reduce life expectancy.
• BRR syndrome
• • Patients may develop medical and surgical complications from lipomas, vascular lesions, and malignancies.
  • Lipomas regress with advancing age; however, 2 children have died in early childhood with severe visceral lipomatosis.
  • Vascular lesions within the CNS have resulted in bleeding with impairment and chronic seizures. Vascular anomalies in other areas can compromise pulmonary function and result in high-output cardiac failure.
  • Patients with BRR have a higher incidence of CNS tumors and can develop metaplastic changes within hamartomatous GI polyps.
  • Mutations within PTEN, a tumor suppressor gene found in patients with BRR, may predispose to malignant transformation, especially thyroid and breast.
• GS
• • Patients may experience complications from malignancies, cardiac fibromas, ophthalmologic abnormalities, and skeletal anomalies.
  • In patients with malignancies, ionizing radiation should be avoided, if possible, to deter the development of basal cell carcinomas.
  • Approximately 3% of patients with GS develop cardiac fibromas, requiring excision if symptomatic.
  • Routine ophthalmologic screening minimizes visual losses from strabismus, glaucoma, and cataracts.
• Patients with Cowden disease may experience complications from hamartomatous polyps, thyroid disease, scoliosis, CNS abnormalities, and malignancies.

Prognosis

• Patients Gardner syndrome have an increased incidence of malignancies, including gastric carcinoma, colonic carcinoma, periampullary carcinoma, biliary tract carcinoma, thyroid carcinoma, osteosarcomas, and adrenal carcinoma.
• Patients with Turcot syndrome have an increased incidence of gastric and colonic carcinomas, basal cell carcinomas, and CNS malignancies.
• Patients with PJS have increased morbidity and mortality rates that arise from the complications of GI polyps and potential development of malignancies.
• Patients with BRR have increased morbidity and mortality rates because of complications of cutaneous lesions (eg, lipomas, arteriovenous malformations) and potential development of malignancies.
• Patients with GS have an increased incidence of malignancies, which include basal cell carcinoma, sarcomas, ovarian carcinomas, medulloblastoma, and astrocytoma.
• Patients with Cowden disease have an increased incidence of CNS abnormalities, as well as malignancies within the cerebellum, breast, skin, and kidneys.

Patient Education

• Patients with Gardner syndrome should undergo routine medical examinations and endoscopic and radiologic evaluations for surveillance of potential malignancies.
• Patients with Turcot syndrome should undergo routine medical examinations and learn surveillance methods for basal cell carcinomas, GI cancer, and breast cancer.
• Routine screening of stools for occult blood and early institution screening for the detection of breast cancer (self-examination, mammography) may improve life expectancy in patients with PJS. The presence of gynecomastia or precious puberty in the patient with suspected PJS should prompt careful evaluation to exclude testicular or gynecologic malignancy.
• Early institution of screening for the detection of breast cancer (self-examination, mammography) and awareness of the increased risk for development of malignancy may improve the life expectancy of patients with BRR.
• Minimizing exposure to ultraviolet light and ionizing radiation in patients with GS may diminish the potential for development of basal cell carcinomas. Establishment of skin self-detection programs may permit early detection of basal cell carcinomas. Patients should undergo routine ophthalmologic, dental, gynecologic, and medical examinations.
• Patients with Cowden disease should undergo routine medical examinations and learn methods of breast self-examination.
• For excellent patient education resources, visit eMedicine's Endocrine System Center. Also, see eMedicine's patient education article Thyroid Problems.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to recognize and properly manage cardiac anomalies in patients with polyposis syndromes with appropriate SBE prophylaxis during endoscopy and colonoscopy presents a potential clinical pitfall.
• Failure to establish routine surveillance strategies in patients with Gardner syndrome to evaluate for malignancy is a potential legal pitfall.
• Failure to establish routine surveillance strategies in patients with Turcot syndrome to evaluate for malignancy and failure to recognize symptoms of underlying CNS tumors represent potential legal pitfalls.
• Delay in diagnosis of intussusception in patients with PJS with high index of suspicion, failure to properly exclude the possibility of testicular or gynecologic malignancy in the child with gynecomastia or precocious puberty, and failure to initiate appropriate surveillance strategies for malignancies (eg, GI, breast) could prove problematic for the clinician.
• Failure to establish early detection strategies for malignancies (eg, breast) is a potential legal pitfall involving patients with BRR.
• Failure to establish routine ophthalmologic screenings for cataracts and glaucoma, failure to perform skin surveillance for basal cell carcinoma, and failure to recognize symptoms of potential malignancy in patients with GS represent potential legal pitfalls.
• Failure to implement early detection strategies for malignancies (eg, breast) is a potential legal pitfall involving patients with Cowden disease.

Special Concerns

• Patients with GS should minimize exposure to ionizing radiation, if possible, to deter the development of basal cell carcinomas.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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