Spitz_Genodermatoses, 3e

Peutz-Jeghers Syndrome

Synonym

Periorificial lentiginosis

Inheritance

AD; serine/threonine kinase 11 ( STK11 ) gene on 19p13 Spontaneous mutation (~10%-20%)

Prenatal Diagnosis

DNA analysis

Incidence

1:8,000-1:200,000; M = F

Age at Presentation

Birth to first few years of life (pigmented macules); first to third decades of life (polyps)

Pathogenesis

STK11 , a tumor suppressor gene, encodes a kinase that catalyzes addition of serine and threonine regulating adenosine monophosphate (AMP)-activated proteins that affect cell polarity, metabolism, and apoptosis; mutations disrupt regulated cell growth and apopto sis, leading to tumor formation Skin Pigmented macules—0.2-7 mm, brown to black in color, variation in shape on periori ficial skin, lips, buccal mucosa, digits, nails, palms, soles, any mucosal surface; all except buccal mucosal lesions may fade with time Gastrointestinal Hamartomatous polyps—small intestine > large intestine, secondary abdominal pain, gastrointestinal bleeding, anemia, intussusception, obstruction; adenocarcinoma may develop within polyps Neoplasm Increased frequency of colorectal carcinoma, followed by breast, stomach, small bowel, and pancreas. Others include lung, sertoli cell tumors, cervical, and ovarian

Key Features

Differential Diagnosis

LEOPARD syndrome (p. 80) Carney complex (p. 82) Laugier-Hunziker syndrome Cronkhite-Canada syndrome Addison disease Gardner syndrome (p. 206)

Laboratory Data

Bowel x-rays, gastroscopy/colonoscopy screening every 1-2 years, polyp biopsy Stool guaiac Mammography Referral to gastroenterologist/surgeon—removal of symptomatic polyps and those > 1.5 cm via endoscopic perioperative panpolypectomy; screening every 3 years if asymp tomatic; cancer surveillance according to published guidelines Referral to obstetrician/gynecologist—regular pelvic/breast examinations/screening Referral to dermatologist—laser surgery

Management

Prognosis

Normal life span if malignancy detected early

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The disorder is caused by mutations in the serine/threonine kinase STK11 gene . . . The pigmented macules on the lips are very amenable to treatment with ruby or Alexandrite lasers . . . We coordinate laser treatment with endoscopy, utilizing the sedation/anesthesia to make the laser “painless” . . . Endoscopy should be routine, with removal of polyps to min imize bowel wall invasion . . . For history buffs, Keller et al. ( Familial Cancer 2002;1:181-185) reviewed the history of Peutz-Jeghers syndrome, including biographic information about Jan Peutz and Harold Jeghers. LE

CLINICAL PEARLS

208