Introduction

Peutz-Jeghers Syndrome, PJS, is a rare condition in a class of conditions known as hamartomatous polyposis syndromes, caused by the inheritance of a mutated gene and is characterised by growths inside the stomach and intestine called gastrointestinal polyps, patches of discolouration on the skin called macules, and an increased risk for developing cancer.^1,2,3,4,5 Patients with PJS are specifically more susceptible to cancers of the colon, rectum, pancreas, stomach, breast, cervix, and uterus.

Of these cancers, colorectal cancer is the most common occurrence in patients with PJS. Those with PJS typically develop cancer at around 40 years of age. Diagnosing the condition is typically done through a physical examination, patient history, genetic testing, and imaging techniques. PJS cannot be prevented nor cured, however, there are several management and treatment options to alleviate signs and symptoms of the condition.^3,4

Cause of Peutz-Jeghers syndrome

PJS is caused by the inheritance of a mutated gene called the STK11 gene. As PJS has a genetic cause, it often runs in families; therefore, a family history of PJS is a predictor for developing the condition. Around 60 to 80 percent of patients with PJS have a family member with the disease.^1,2,3

Signs and symptoms of Peutz-Jeghers syndrome

Signs and symptoms of PJS typically present for the first time during childhood, specifically before 10 years of age. The characteristic presentation of PJS is growths inside the stomach and intestine called gastrointestinal polyps and patches of discolouration on the skin called macules.¹

Gastrointestinal polyps

Gastrointestinal polyps tend to appear during the early years of life, however, signs and symptoms of these typically show themselves between the ages of 10 and 30 years. Several signs and symptoms can result from gastrointestinal polyps:¹

• Abdominal pain
• Vomiting
• Diarrhoea
• Bleeding from the rectum

Macules

Macules typically appear as dark blue or dark brown freckles surrounding the eyes, mouth, mucus inside the mouth, nostrils, fingers, and anus, though often fade away as a patient ages, typically by puberty or adulthood. Macules on mucus inside the mouth, however, tend to persist in adulthood.¹

Diagnosis of Peutz-Jeghers syndrome

Diagnosing PJS can involve several techniques, these being physical examination, patient history, genetic testing, and imaging techniques. When diagnosing PJS, it is important that it be distinguished from other hamartomatous polyposis syndromes, these being, Bannayan-Riley Ruvalcaba syndrome and Cowden syndrome, as they can present similarly to PJS.^3,4

Physical examination

A physical examination provides your doctor with an opportunity to inspect your body, specifically looking for any abnormalities. Since PJS can cause macules, the physical inspection can be integral for the condition’s diagnosis, as it provides an opportunity for these to be identified by your doctor.^1,6

Patient history

In a patient history, a doctor will ask you a series of questions related to your health to gather information about your health and to help confirm a diagnosis of a condition.⁶ For example, a doctor may ask about your family history and whether you know if PJS runs in your family.^2,3 Furthermore, during the patient history, you will be asked to disclose the signs and symptoms you’ve been experiencing, helping your doctor confirm a diagnosis of the condition. You will also be provided with an opportunity to ask any questions.⁶

Genetic testing

Genetic testing can reveal whether you have the mutated gene, that is STK11, that causes PJS. Genetic testing is mostly recommended for patients with a family history of PJS. Genetic testing can allow PJS to be diagnosed before signs and symptoms appear. Genetic testing typically involves a sample of your blood or saliva being collected and then sent to a laboratory to be analysed.^1,7,8

Imaging techniques

Imaging techniques, specifically endoscopies or x-rays, can be used to detect gastrointestinal polyps, a characteristic feature of PJS.¹

Endoscopies involve a tube being passed into an opening to view the inside of the body. In the case of suspected PJS, specifically, this tube will be passed into the stomach or intestine, either through the mouth or your anus.¹⁰

X-rays are a quick and painless procedure where x-rays are passed through the body through beams being focussed at the body in order to take images of inside it.¹¹

Management and treatment of Peutz-Jeghers syndrome

Surveillance

As patients with PJS are at an increased risk of having cancer, it is important that, as a part of their management and treatment, they undergo surveillance for cancer. Surveillance can involve a range of imaging techniques, such as endoscopies.³

Surgery

Surgery can be useful in treating gastrointestinal polyps by removing them. This can help stop signs and symptoms and an increased cancer risk associated with gastrointestinal polyps. Some patients may benefit more than others from having surgery, depending on the number and size of gastrointestinal polyps that they have.²

Outlook for Peutz-Jeghers syndrome

Patients with PJS are at an increased risk of cancer. Patients with PJS are specifically more susceptible to cancers of the colon, rectum, pancreas, stomach, breast, cervix, and uterus. Of these cancers, colorectal cancer is the most common occurrence in patients with PJS, with patients having about a 40 percent chance of acquiring this cancer.

Stomach cancer also poses a particular risk for those with PJS, with there being about a 30 percent chance that those with PJS will be diagnosed with this cancer. For those assigned female at birth, specifically, they are most at risk of breast cancer, facing a 30 to 50 percent chance of acquiring breast cancer.

Those with PJS typically develop cancer at around 50 years of age, and by age 60 years, about half of patients with PJS have cancer. However, surveillance can help prevent cancer from occurring or ensure that it is diagnosed and, therefore, treated early, minimising cancer-associated complications.^2,3

FAQs

How common is PJS?

PJS is a rare condition, occurring in about one in 25,000 to 300,000 births. Any ethnicity can be affected and there is no difference in the condition’s incidence in those assigned female at birth and those assigned male at birth.³

What are the gastrointestinal symptoms associated with PJS?

Gastrointestinal polyps, which are growths inside the stomach and intestine, are characteristic of PJS. They tend to appear during the early years of life and can result in signs and symptoms that typically show between the ages of 10 and 30 years. These signs and symptoms include abdominal pain, vomiting, diarrhoea, and bleeding from the rectum.¹ 

Is PJS associated with an increased risk of cancer?

PJS is associated with an increased risk of cancer. Patients with PJS are specifically more susceptible to cancers of the colon, rectum, pancreas, stomach, breast, cervix, and uterus. Of these cancers, colorectal cancer is the most common occurrence in patients with PJS. For those assigned female at birth specifically, breast cancer poses the highest risk of occuring.³

Is genetic counselling recommended for those with PJS?

Genetic counselling is recommended for patients with PJS if they have a family history of the condition and are planning on having a child.³ Genetic counselling involves a genetic counsellor helping you understand your risks of having a child with PJS and providing education on genetic disease, as well as answering any questions that you may have related to the matter.¹¹

Are there any reproductive considerations for individuals with PJS?

PJS is a genetic condition that can run in families. Therefore, those with the condition run an increased risk of having a child with PJS. 

Can PJS be prevented or cured?

PJS cannot be prevented as it is caused by inheritance of a mutated gene. PJS also cannot be cured, though there are several management and treatment options to alleviate signs and symptoms of the condition.^3,4

Summary

PJS is a rare genetic condition in a class of conditions known as hamartomatous polyposis syndromes, caused by the inheritance of a mutated gene, specifically a gene called STK11. The condition is characterised by growths inside the stomach and intestine called gastrointestinal polyps, patches of discolouration on the skin called macules, and an increased risk of developing cancer.

Colorectal cancer is the most common form of cancer in patients with PJS, with cancer typically occurring at around 40 years of age. Diagnosis of PJS can involve a physical examination, patient history, genetic testing, and imaging techniques. Management and treatment of the condition typically aim to alleviate signs and symptoms, with a cure for the condition currently not available.