The 2, classic, clinical manifestations of Peutz-Jeghers syndrome are mucocutaneous pigment macules and hamartomatous GI polyps. The average age of diagnosis is 23; the first presentation is often from bowel obstruction due to intussusception from the hamartomatous polyps in the GI tract.

Pigmented mucocutaneous dark blue, brown, to black macules, are present in over 95% of individuals with Peutz-Jeghers syndrome. Most commonly distributed on the lips, perioral areas, buccal mucosa, eyes, nostrils, fingertips, palms, soles, and perianal areas. The macules are rarely present at birth but appear in childhood usually before the age of 5 with oral pigmentation being the first to appear during the first year of life. The macules may fade during puberty and adulthood, except for those on the buccal mucosa which remain into adulthood. No malignant transformation is associated with the melanocytic macules.

Benign hamartomatous polyps with low malignancy-risk develop within the first decade of life and are found anywhere along the GI tract, most commonly the jejunum and extraintestinal sites including but not limited to the bronchus, renal pelvis, and urinary bladder.

Complications of Peutz-Jeghers syndrome include intussusception or obstruction of the GI lumen by the polyps. This may result in abdominal pain or ulceration of the bowels. Up to 69% of patients experience intussusception of the small intestine, with the first event occurring between the ages of 6 and 18 years. GI polyps can also cause chronic bleeding leading to anemia.

Peutz-Jeghers syndrome is based on clinical findings of having at least 2 of the 3 listed clinical criteria for a positive diagnosis:

1. Family history 
2. Multiple dark blue to brown pigmented (macules) lesions on the mucous membranes and skin are most often intraoral on the buccal mucosa or gingiva, lips, perioral, fingertips, palms, and soles
3. Hamartomatous intestinal polyps

Mucocutaneous findings are non-specific for Peutz-Jeghers syndrome; other differentials must be considered. Molecular and genetic testing can aid in confirming the diagnosis

The mainstay of management of patients with Peutz-Jeghers syndrome includes surveillance, prevention of manifestations of the condition, and treatment of complications.[1][2][3]

Surveillance

Peutz Jeghers patients may develop GI polyposis as early as 10 years old, with the small intestine as the most common site. Therefore, it is imperative to evaluate the small intestine with upper endoscopy in addition to colonoscopy beginning at early adolescence.

Due to the increased risk of malignancy in Peutz-Jeghers syndrome surveillance recommendations includes the following:

Upper GI Tract 

Upper endoscopy 

• Baseline screening beginning at 12 years old
• If polyps found repeat annually 
• In absence of polyps repeat every 2-3 years into adulthood

Colorectal

Colonoscopy

• Baseline screening beginning at 12 years old or earlier if reported symptoms
• If polyps found repeat annually
• In absence of polyps repeat at 1-3 year intervals

Pancreatic

Magnetic resonance cholangiopancreatography (MRCP) and/or endoscopic ultrasound: Beginning at 25 to 30 years old; Repeat every 1 to 2 years

Breast

Breast examination: 6-month clinical breast examination beginning at age 25

Breast mammogram: Beginning at age 25Gynecologic

Papanicolaou smear: Annually

Transvaginal ultrasound: Consider yearly transvaginal ultrasound beginning at age 18

Testicular

Consider annual examination and yearly ultrasound beginning at age 10.

Prevention

Genetic counseling is recommended to individuals that have a family history of Peutz-Jeghers syndrome and are planning to have children

In female patients with Peutz Jeghers prophylactic mastectomy to manage the increased risk for breast cancer and hysterectomy and bilateral salpingo-oophorectomy after childbearing completion or age 35 to prevent gynecologic malignancy could be considered.[4][5]

Juvenile polyposis (JPS), is an autosomal dominant inherited condition which presents with hamartomatous polyps of the small intestine due to mutations in the BMPR1A, SMAD4 or ENG genes; however, dermatological findings of PJS are not appreciated.[6][7]

Peutz-Jeghers syndrome, Bannayan-Riley Ruvalcaba syndrome (BRRS), and Cowden Syndrome belong to a family of hamartomatous polyposis syndromes. Therefore, they share similar clinical features such as gastrointestinal polyposis, but they differ in genetic loci mutation. BRRS and Cowden syndromes belong to the PTEN1 gene mutations, with pigmented lesions most commonly on the glans penis. Bannayan-Riley Ruvalcaba patients present with macrocephaly, developmental delay, lipomas, and vascular abnormalities and Cowden syndrome patients present with trichilemmomas, facial papules/oral papillomas, and acral keratoses.

Pigmented intraoral mucocutaneous macules can be found in Laugier-Hunziker syndrome (LHS) but appear later in life after childhood. Additional dermatological findings of longitudinal hyperpigmented bands (melanonychia) on toe and fingernails are also present. Laugier-Hunziker syndrome is not associated with gastrointestinal polyposis.

Peutz-Jeghers syndrome patients are at an increased risk for malignancies. Earlier screening and surveillance is recommended.

• Bowel obstruction
• Rectal bleeding
• Mesenteric ischemia
• Gastric outlet obstruction
• Iron deficiency anemia

An interprofessional approach to PJS is recommended. Peutz-Jeghers syndrome (PJS) is a hereditary cancer syndrome characterized by GI polyposis, mucocutaneous pigmented macules and cancer predisposition. Patients with PJS are at an increased risk for developing GI cancers of the colorectal, pancreatic, and gastric organs besides a wide variety of non- gastrointestinal epithelial malignancies such as breast, uterine and cervical cancer, lung and tumors of the ovaries and testicles. An interprofessional team consisting of a geneticist, gastroenterologist, general surgeon, dermatologist, urologist, and gynecologist is recommended to decrease the morbidity and mortality of this syndrome. The primary care provider and nurse practitioner should refer these patients to the appropriate specialist as soon as the diagnosis is made. A consult should take place with a board-certified oncology pharmacist regarding the patient's medication regimen, for both cancer and non-cancer meds, and an oncology specialty nurse can assist in the monitoring, answer patient questions, and report any changes in status to the managing clinician immediately. The outlook for most patients is guarded. For those who remain cancer-free, the long-term outlook is good, but once malignancies develop, the lifespan is shorter.[8][9][10]