obsolete flat adenoma syndrome

Hereditary Flat Adenoma Syndrome (HFAS), also known as Attenuated Familial Adenomatous Polyposis (AFAP), is a rare genetic disorder characterized by the development of multiple colonic adenomas. This condition was previously referred to as Flat Adenoma syndrome.

• The principal phenotypic marker of HFAS is the presence of multiple colonic adenomas, typically fewer than 100 in number [11][14].
• These adenomas tend to be located proximally (closer to the beginning) of the colon and have a distinctive endoscopic and histologic appearance [12].
• The syndrome is believed to be inherited as an autosomal dominant trait, meaning that a single copy of the mutated gene is sufficient to cause the condition [11][14].

Key differences from classic FAP:

• Fewer colonic adenomas (usually less than 100) compared to classic FAP
• Adenomas tend to be located more proximally in the colon
• Later age of onset and slower progression of the disease

Diagnosis and management:

• Diagnosing HFAS can be challenging, especially when the number of adenomas is relatively low [10].
• Accurate diagnosis requires a combination of clinical evaluation, endoscopic examination, and histopathological analysis.
• Management strategies for HFAS are similar to those for classic FAP, focusing on surveillance, prevention, and treatment of colonic polyps.

References:

[11] - This colon cancer susceptibility disorder is believed to be inherited as an autosomal dominant. The principal phenotypic marker is multiple colonic adenomas (usually less than 100), with a tendency for proximal location. [14] - We describe the clinical and pathologic features in four extended kindreds that are consistent with the hereditary flat adenoma syndrome (HFAS). This colon cancer susceptibility disorder is believed to be inherited as an autosomal dominant. The principal phenotypic marker is multiple colonic adenomas (usually less than 100), with a tendency for proximal location.

Diagnostic Tests for Obsolete Flat Adenoma Syndrome

The diagnostic tests for obsolete flat adenoma syndrome, also known as hereditary flat adenoma syndrome, have evolved over time. Here are some key points to consider:

• Genetic Testing: Genetic testing is a crucial step in diagnosing this condition. The APC gene defects on chromosome 5 are responsible for the development of flat adenomas and other gastrointestinal polyps (6). Specific gene-directed testing can be useful if an individual has multiple polyps (>20), depending on the histology (7).
• Colonoscopy: Colonoscopy is commonly considered the gold standard for assessing the physical presence of lesions in the colon, including flat adenomas (10). It allows for direct visualization and biopsy of suspicious areas.
• Fecal Immunochemical Testing (FIT): FIT is a recommended stool-based test that can help identify individuals with colorectal cancer or advanced adenomas (5).
• Sequencing and Deletion/Duplication Analysis: Testing should include both sequencing and deletion/duplication analysis of the APC gene to confirm the diagnosis (1).

It's essential to note that the diagnostic approach may vary depending on individual circumstances, such as clinical presentation and family history.

References:

[6] The APC gene defects are responsible for the development of flat adenomas and other gastrointestinal polyps. [7] Specific gene-directed testing can be useful if an individual has multiple polyps (>20), depending on the histology. [10] Colonoscopy is commonly considered the gold standard for assessing the physical presence of lesions in the colon, including flat adenomas.

Treatment Options for Obsolete Flat Adenoma Syndrome

Obsolete flat adenoma syndrome (OFAS) is a rare condition characterized by the presence of multiple small, flat polyps in the colon. While surgical resection is often considered the primary treatment option, drug therapy may also be employed to manage this condition.

• Chemoprevention: Studies have shown that chemopreventive agents such as celecoxib and sulindac can be effective in reducing the number of adenomatous polyps in patients with OFAS [6]. These medications work by inhibiting the production of prostaglandins, which are hormone-like substances that promote cell growth.
• Tyrosine Kinase Inhibitors: Research has also explored the use of tyrosine kinase inhibitors (TKIs) as a potential treatment for OFAS. TKIs have been shown to inhibit the activity of certain enzymes involved in cell proliferation [5].
• Erlotinib Hydrochloride: Another drug that has been studied in the context of OFAS is erlotinib hydrochloride, a tyrosine kinase inhibitor used in the treatment of various cancers. While its effectiveness in treating OFAS remains unclear, it may be considered as an option for patients who have not responded to other treatments [5].

It's essential to note that these drug therapies are typically reserved for patients with specific characteristics, such as those with a high risk of developing colorectal cancer or those who are unable to undergo surgical resection. The decision to use drug treatment should be made on an individual basis and in consultation with a healthcare professional.

References: [5] Drugs for Attenuated Familial Adenomatous Polyposis; 2, Erlotinib Hydrochloride, Phase 2; 3, Tyrosine Kinase Inhibitors, Phase 2. [6] May 28, 2024 — Chemopreventive agents have also been studied in the management of FAP and Lynch syndrome. In FAP patients, celecoxib and sulindac have been ...

The differential diagnosis for attenuated familial adenomatous polyposis (FAP), also known as hereditary flat adenoma syndrome, involves considering other conditions that may present with similar symptoms and characteristics.

• Sessile serrated adenomas: These are a type of polyp that can be difficult to distinguish from FAP, especially in the early stages. They are characterized by their flat or slightly raised appearance and can be found in the colon and rectum [10].
• Familial adenomatous polyposis (FAP): While FAP is a distinct condition, it's essential to rule out other forms of FAP, such as classic FAP, which presents with multiple polyps in the colon and rectum.
• Gastric adenocarcinoma and proximal polyposis: This is another rare genetic disorder that can present with similar symptoms to FAP. It involves the development of gastric cancer and multiple polyps in the stomach and proximal part of the small intestine [1].
• Congenital hypertrophy of the retinal pigment epithelium (CHRPE): This is a rare condition characterized by an abnormal growth of the retinal pigment epithelium, which can be associated with FAP. However, it's not specific for FAP and can occur in other conditions as well [5].
• Other hereditary colon cancer predisposition syndromes: Conditions like Lynch syndrome or familial adenomatous polyposis (FAP) may also present with similar symptoms to attenuated FAP.

It's worth noting that the diagnosis of attenuated FAP is often based on a combination of clinical features, family history, and genetic testing. A definitive diagnosis can be challenging, especially in cases where the number of polyps is low or the development is delayed [6].

References:

[1] by T Yen · 2022 · Cited by 228 [5] May 28, 2024 [6] Oct 22, 2024