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Clinical Quiz

Fitzgerald, Joseph F.1; Troncone, Riccardo2; Bader, Ali A.*; Biesecker, Leslie G.†,3

Journal of Pediatric Gastroenterology and Nutrition: July 2003 - Volume 37 - Issue 1 - p 71,90

1NASPGHAN Clinical Quiz Editor

2ESPGHAN Clinical Quiz Editor


*Department of Pediatric Gastroenterology and Nutrition, Children's National Medical Center, George Washington University, Washington, DC; †Genetic Diseases Research Branch, National Human Genome Research Institute, NIH, Bethesda, MD

A14-year-old boy presented with a history of severe anemia and fatigue. There was no history of nausea, vomiting, diarrhea, abdominal pain, hematemesis, hematochezia or melena. His past medical history was remarkable for presentation at seven years of age with rectal prolapse, anemia, thrombocytopenia, hypersplenism, generalized left-sided hemihypertrophy and mediasternal enlargement. A bone marrow biopsy obtained at that time showed a decreased myeloid to erythroid ratio with normal karyocytes. He underwent a partial colectomy, splenectomy and thymoma resection.

At the time of his recent visit his labs revealed WBC 13.3 k/μl, Hgb 8.8 g/dl, HCT 29.4%, MCV 82.9, RDW 22.8%, PLT 464 K/μl, albumin 2.2 g/dl, iron 58 μg/dl, transferrin 216 mg/dl and iron saturation 19%. Upper gastrointestinal endoscopy revealed marked patchy thickening of the gastric mucosa on the greater curvature and in the prepyloric region (Fig. 1), and colonic mucosal hypertrophy was evident in the rectum and cecum at colonoscopy (Fig. 2).

FIG. 1

FIG. 1

FIG. 2

FIG. 2

Question: What is the etiology of these abnormal mucosal findings?

A. Ménétrièr's disease

B. Lymphoma

C. Adenocarcinoma

D. Proteus syndrome

E. Allergic enteropathy

Answer: D Proteus syndrome. Biopsies revealed minimal, nonspecific abnormalities, including mild inflammation and some regenerative changes.

Comment: The term Proteus syndrome was coined by Wiedemann et al in 1983, who named the disorder after Proteus, the sea god of Greek Mythology, who took on many forms to avoid capture (1).

Proteus syndrome is a rare disorder with postnatal overgrowth of many tissues, including soft tissues and bone, lipomas, planter hyperplasia, and linear verrucous nevi, among other findings (2). Essentially, any tissue or organ can manifest overgrowth, including the CNS, thymus, spleen, gut and vascular system, in addition to the manifestations listed above.

The etiology of Proteus syndrome remains unknown; however, the sporadic nature, patchy involvement and discordant monozygotic twins suggest that the disorder is caused by a postzygotic mutation with resulting mosaicism (3). The pattern of overgrowth suggests a defect in the local regulation or production of specific tissue factors or their receptors (4).

Over 100 cases of Proteus syndrome have been reported, but the incidence is unknown. There is evidence that Joseph Carey Merrick, the so-called “Elephant Man”, had Proteus syndrome and not neurofibromatosis as previously thought (5).

Most case reports describe children. There appears to be an increased early mortality from the disorder. One common cause is deep venous thrombosis and fatal pulmonary embolism which has occurred in children as young as nine years of age (6). There are several adults with the syndrome, suggesting the potential for a normal lifespan in mildly affected patients.

Treatment is primarily symptomatic with thoughtful use of surgical procedures to debulk overgrown tissues and correct orthopedic deformities.

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1. Wiedemann HR, Burgio GR, Aldenhoff P, et al. The proteus syndrome. Europ J Pediatr 1983;140:5-12.
2. Biesecker LG. The multifaceted challenges of Proteus syndrome. J Am Med Assoc 2001;285:2040-2043.
3. Cohen MM Jr. Proteus syndrome: Clinical evidence for somatic mosaicism and selective review. Am J Med Genet 1993;47:645-652.
4. Clark RD, et al. Proteus syndrome: An expanded phenotype. Am J Med Genetic 1987;27:99-118.
5. Cohen MM Jr. The Elephant Man did not have neurofibromatosis. Proc Greenwood Genetic Center 6. 1987;187-192.
6. Slavotinek AM, Vacha SV, Peters KF, Biesecker LG. Sudden death caused by pulmonary thromboembolism in Proteus syndrome. Clin Genet 2000;58:386-389.
© 2003 Lippincott Williams & Wilkins, Inc.