Makindo Medical Notes.com

Related Subjects: |Autosomal Dominant |Autosomal Recessive |X Linked Recessive

Patients with FAP have congenital hypertrophy of the retinal pigmented epithelium

About

• 0.5-1% of Colorectal cancer. Approx 1 in 10,000
• It is inherited as an autosomal dominant defect
• Average age to develop colorectal cancer is 39 years old
• Average age for colorectal cancer in attenuated FAP is 55 years.

Genetics

• FAP usually due to mutations in the APC gene, it is inherited in an autosomal dominant pattern which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.
• FAP results from mutations in the MUTYH gene, it is inherited in an autosomal recessive pattern which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but do not show signs and symptoms of the condition.
• Colorectal cancer is seen in 100% of those affected

Aetiology

• APC Genes is on chromosome 5q band 21 or 22.
• Loss of one of two Adenomatous polyposis coli (APC) genes
• There is hypertrophy of the retinal pigment layer which may be detected in the infant
• The APC genes act as caretakers or a "gatekeeper" gene.
• Milder form of the disease called attenuated familial adenomatous polyposis, in which polyp growth is delayed.
• Desmoid tumour tend to recur after they are surgically removed.

Clinical

• Development of > 100 colorectal polyps is needed for diagnosis
• Often presents in teenage years
• Untreated patients develop bowel cancer by the age of 40
• Dental cysts and jaw osteomas, retinal pigmentation
• Epidermoid and desmoid cysts, Hamartomatous gastric polyps

Investigations

• Surveillance Colonoscopy shows multiple polyps usually non-malignant - the number of polyps increases with age, and hundreds to thousands of polyps can develop in the colon
• DNA studies identify individuals

Management

• Regular surveillance colonoscopy starts in the teenage years.
• Plan for elective surgery e.g. Panproctocolectomy + end ileostomy
• Colectomy and ileorectal anastomosis (rectum needs inspection and removal of polyps)
• Proctocolectomy with ileal pouch-anal anastomoses (Now surgery of choice)
• Screen other members of the family