eMedicine Specialties > Dermatology > Pediatric Diseases

Proteus Syndrome: Differential Diagnoses & Workup

Author: Matthew J Mahlberg, MD, Resident Physician, Department of Dermatology, New York University School of Medicine
Coauthor(s): Mina Yassaee, University of Pennsylvania School of Medicine; William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
Contributor Information and Disclosures

Updated: Dec 10, 2008

Differential Diagnoses

Klippel-Trenaunay-Weber Syndrome
Maffucci Syndrome
Neurofibromatosis

Other Problems to Be Considered

Carefully distinguish Proteus syndrome from other overgrowth disorders, particularly Klippel-Trenaunay syndrome, hemihyperplasia/lipomatosis syndrome, and neurofibromatosis type 1.26 Several other syndromes can also be considered in the differential diagnosis11 ; these are discussed below.

Vascular syndromes

The classic definition of Klippel-Trenaunay syndrome is the triad of vascular stain, soft tissue and/or bony hypertrophy, and venous varicosities. It often involves vascular malformation involving the lower or upper limbs, but usually only 1 limb is affected. The vascular (ie, capillary, lymphatic, and venous) malformations always exist in combination. Overgrowth is present at birth; commonly, this is more severe than that in Proteus syndrome. Moreover, Klippel-Trenaunay syndrome lacks subcutaneous tumors, palmar and/or plantar cerebriform hyperplasia, and cranial exostoses, which are usually found in Proteus syndrome patients.27 The delayed onset of cerebriform hyperplasia often leads to the misdiagnosis of Proteus syndrome as Klippel-Trenaunay syndrome in neonates and infants.11

Parkes-Weber syndrome is a vascular malformation involving the upper and lower limbs. It is characterized by a diffuse capillary blushing, warmth, and underlying arteriovenous shunts.

Maffucci syndrome is characterized by hemangiomas and enchondromas.

Syndromes with pigmentation and lipomatosis

Neurofibromatosis type 1 involves café au lait macules, axillary freckling, Lisch nodules, and neurofibromas, rather than epidermal nevi and hamartomas.

Bannayan-Riley-Ruvalcaba syndrome, which is characterized by macrocephaly, lipomas, capillary malformations, and polyposis of the colon and rectum, does not cause asymmetric growth, cranial exostoses, epidermal nevi, or palmar or plantar changes.

Patients with hemihyperplasia lipomatosis syndrome lack the progressive overgrowth seen in patients with Proteus syndrome.

Encephalocraniocutaneous lipomatosis has been considered a circumscribed form of Proteus syndrome, although some authors believe that Proteus syndrome and encephalocraniocutaneous lipomatosis are different entities.28

Workup

Imaging Studies

  • Imaging studies are useful in helping to establish the diagnosis of Proteus syndrome and in tracking the progression of the disease.
  • Radiography of the skull, vertebral column, long bones, and pelvis: The most characteristic forms of overgrowth are macrodactyly, clinodactyly, asymmetrical hypertrophy of a limb, vertebral body abnormalities, and hyperostosis.20
  • Comparative radiographic study of the hands and feet: The most characteristic non-cutaneous features are progressive asymmetric macrodactyly, hemihypertrophy of any part of the skeleton, scoliosis and spinal canal stenosis, macrocephaly, and exostoses, especially of the skull.
  • Intracranial MRI: This is an essential initial examination to evaluate for malformations of the CNS that may be associated with mental retardation or seizures. Such findings may include multiple meningiomas, polymicrogyria, and periventricular heterotopias.
  • Abdominal MRI: Even in the absence of symptoms, abdominal MRI is important to exclude intra-abdominal lipomas. If present, these can behave aggressively, invading adjacent structures.
  • High-resolution chest CT scanning: This examination may be useful in evaluating pulmonary cystic malformations.

Other Tests

  • Skin biopsy: Skin biopsy should be considered to confirm the clinical diagnosis of a cerebriform connective-tissue nevus. See Proteus syndrome diagnostic criteria, category A, in Physical.
  • Karyotype analysis: Chromosome analysis may reveal a translocation or deletion that may suggest a candidate gene.
  • Electroencephalography: Although most patients appear to be of normal intelligence, mental retardation may occur. Seizures have also been reported.

Procedures

  • The ongoing evaluation of the patient with Proteus syndrome should include the following procedures12 :
    • Serial clinical photography
    • Initial skeletal survey with targeted follow-up radiography
    • MRI of all clinically affected areas
    • MRI of the chest and abdomen in the absence of symptoms
    • Consultation with a dermatologist, followed by biopsy if indicated
    • Consultation with an orthopedic surgeon, followed by surgical treatment if indicated
    • Ongoing treatment from a geneticist, pediatrician, or both
    • Consultations with a neurologist and an ophthalmologist
    • Referral to family support group

Histologic Findings

The histologic findings in Proteus syndrome are specific to the particular type of lesion. The histology of cerebriform connective-tissue nevi and epidermal nevi are discussed in  History and Physical, along with a description of their clinical manifestations.

More on Proteus Syndrome

Overview: Proteus Syndrome
Differential Diagnoses & Workup: Proteus Syndrome
Treatment & Medication: Proteus Syndrome
Follow-up: Proteus Syndrome
Multimedia: Proteus Syndrome
References
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References

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  14. del Rosario Barona-Mazuera M, Hidalgo-Galván LR, de la Luz Orozco-Covarrubias, Durán-McKinster C, Tamayo-Sánchez L, Ruiz-Maldonado R. Proteus syndrome: new findings in seven patients. Pediatr Dermatol. Jan-Feb 1997;14(1):1-5. [Medline].

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Further Reading

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Keywords

PS, hamartomatous disorder, multifarious mesodermal malformation, plurifocal overgrowth, partial gigantism, regional gigantism

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Contributor Information and Disclosures

Author

Matthew J Mahlberg, MD, Resident Physician, Department of Dermatology, New York University School of Medicine
Matthew J Mahlberg, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Coauthor(s)

Mina Yassaee, University of Pennsylvania School of Medicine
Mina Yassaee is a member of the following medical societies: Phi Beta Kappa and Sigma Xi
Disclosure: Nothing to disclose.

William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: elsevier Royalty Other; american college of physicians Honoraria Other

Medical Editor

Albert C Yan, MD, Section Chief, Associate Professor, Department of Pediatrics, Section of Dermatology, Children's Hospital of Philadelphia and University of Pennsylvania
Albert C Yan, MD is a member of the following medical societies: American Academy of Dermatology, American Academy of Pediatrics, Society for Investigative Dermatology, and Society for Pediatric Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Jeffrey J Miller, MD, Associate Professor of Dermatology, Penn State University College of Medicine; Staff Dermatologist, Penn State Milton S Hershey Medical Center
Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Professors of Dermatology, North American Hair Research Society, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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