Sandbox:Hamid

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Hamid Qazi, MD, BSc [2]

Historical Perspective

===Discovery===

• Peutz-Jeghers syndrome was first discovered by Dr. Connor, a British, in 1895 in identical twin sisters.

• The association between gastrointestinal polyposis with distinctive pigmentation of the skin and Peutz-Jeghers syndrome was made in 1921 by Dr. Johannes Peutz of Holland.
• In 1949, Dr. Harold Jeghers of United States was the first to discover the association between combination of intestinal polyposis and skin pigmentation, and the development of Peutz-Jeghers syndrome.
• In 1954, A. Bruwer used the eponym Peutz-Jeghers syndrome
• In 1998, serine/threonine-protein kinase 11 alias LKB1 (STK11/LKB1) gene mutations were first implicated in the pathogenesis of Peutz-Jeghers syndrome.

Classification

• There is no established system for the classification of [disease name].

OR

• [Disease name] may be classified according to [classification method] into [number] subtypes/groups:
  • [Group1]
  • [Group2]
  • [Group3]
  • [Group4]

OR

• [Disease name] may be classified into [large number > 6] subtypes based on:
  • [Classification method 1]
  • [Classification method 2]
  • [Classification method 3]
• [Disease name] may be classified into several subtypes based on:
  • [Classification method 1]
  • [Classification method 2]
  • [Classification method 3]

OR

• Based on the duration of symptoms, [disease name] may be classified as either acute or chronic.

OR

• If the staging system involves specific and characteristic findings and features:
• According to the [staging system + reference], there are [number] stages of [malignancy name] based on the [finding1], [finding2], and [finding3]. Each stage is assigned a [letter/number1] and a [letter/number2] that designate the [feature1] and [feature2].

OR

• The staging of [malignancy name] is based on the [staging system].

OR

• There is no established system for the staging of [malignancy name].

Pathophysiology

Pathogenesis

• It is thought that Peutz-Jeghers syndrome is the result of deletion or partial deletion of STK11 (LBK1) gene, located on chromosome 19p13.3.
• STK11 protein plays an important role in second messenger signal transduction and is found to regulate cellular proliferation, controls cell polarity, and responds to low energy states.
• In Mammalian studies, STK11 is shown in the inhibition of AMP-activated protein kinase (AMPK), and signals downstream to inhibit the mammalian target of rapamycin (mTOR).
  • The mTOR pathway is dysregulated in Peutz-Jeghers syndrome.

Pathology

• Peutz-Jeghers syndrome associated polyps have a unique smooth muscle core that arborizes throughout the polyp.
  • These polyps can only be differentiated from other polyp types by histopathology.
  • insert image

Causes

• Peutz-Jeghers syndrome is caused by STK11 gene mutation
• Variable penetrance

Epidemiology and Demographics

Prevalence

• The prevalence of Peutz-Jeghers syndrome is estimated to be 1 in 8300 to 250000
• Most likely prevalence is 1 in 100000

Age

• Peutz-Jeghers syndrome affects individuals between the ages of 10 to 30 years; average age of diagnosis is 23 years for males and 26 years for females.

Gender

• Males and females are equally affected.

Risk Factors

• There are no established risk factors for Peutz-Jeghers syndrome.

Screening

• According to the American College of Gastroenterology (ACG) and the National Comprehensive Cancer Network (NCCN), screening for Peutz-Jeghers syndrome by physical exam, complete blood work for iron deficiency anemia, and endoscopy are recommended every year among patients with Peutz-Jeghers Syndrome.

Natural History, Complications, and Prognosis

Natural History

• The symptoms of Peutz-Jeghers syndrome usually develop in the first decade of life, and start with symptoms such as hyperpigmentation, abdominal pain, and rectal bleeding.
• If left untreated, patients with Peutz-Jeghers syndrome may progress to develop colon cancer, breast cancer, and gastrointestinal cancers.
• Extraintestinal manifestation include pancreatic, lung, breast, uterine, ovarian and testicular malignancies.

Complications

• Common complications of Peutz-Jeghers syndrome include:
  • Intussusception
  • Gastric outlet obstruction
  • Extraintestinal polyps

Prognosis

• Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.
• Depending on the extent of the [tumor/disease progression/etc.] at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as poor/good/excellent.
• The presence of [characteristic of disease] is associated with a particularly [good/poor] prognosis among patients with [disease/malignancy].
• [Subtype of disease/malignancy] is associated with the most favorable prognosis.
• The prognosis varies with the [characteristic] of tumor; [subtype of disease/malignancy] have the most favorable prognosis.