Genetics of Proteus Syndrome Workup

  • Author: Beth A Pletcher, MD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Mar 18, 2010
 

Laboratory Studies

  • No molecular test is currently available for Proteus syndrome.
  • Platelet estimates may be indicated for patients with numerous vascular malformations or splenomegaly, especially those with a history of easy bruising or petechiae.
  • A coagulation workup may be indicated preoperatively for patients with Proteus syndrome in light of the apparent increased risks for thrombotic events such as deep vein thrombosis (DVT) or pulmonary embolism (PE).
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Imaging Studies

  • Radiography
    • A baseline skeletal survey is recommended for all individuals at the time of diagnosis, with follow-up radiography as necessary.
    • Consider anteroposterior (AP) and lateral spine radiography for an affected child with clinical evidence of scoliosis or kyphosis.
    • Radiography of enlarged digits or limbs may be necessary if orthopedic intervention is considered.
  • MRI or CT scanning
    • MRI or CT scanning may help evaluate intracranial anatomy, especially cranial asymmetry that might be associated with cerebral cortex overgrowth. MRI of the head is also an important screening tool for intracranial malformations in children with seizures or developmental delay.[11]
    • A 3-dimensional CT scan may be very useful in evaluating bony overgrowth of the cranium or facial structures; however, both soft tissue and bony involvement are typical for the related hemihyperplasia.
    • MRI of the thorax, abdomen, or extremities may be necessary to define the boundaries of a subcutaneous lesion such as a vascular malformation or lipoma that extends deep into soft tissues. Abdominal and thoracic MRIs are vital screening tools even when clinical symptoms are absent because undiagnosed internal lipomas can cause future problems.
    • High-resolution chest CT scanning may especially help identify pulmonary cystic malformations, which may be suspected in patients with recurrent pneumonias, atelectasis, or respiratory compromise.[11] Postprocessing CT densitovolumetry may also help to more clearly delineate the extent of cystic lung involvement in patients with pulmonary manifestations.[12]
    • Multidetector CT with intravenous contrast may be used to identify a PE when this becomes a clinical concern.[11]
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Other Tests

  • Electroencephalography is indicated for any patient with a history or symptoms suggesting seizures.
  • Pulmonary function tests may help evaluate patients with respiratory symptoms.
  • Venograms, Doppler studies, or ventilation/perfusion (V/Q) studies may be helpful diagnostic tools in patients with symptoms suggestive of DVT or PE.
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Histologic Findings

  • Connective tissue nevi resemble tightly compacted, collagen-rich connective tissue.
  • Epidermal nevi generally exhibit a combination of hyperkeratosis, parakeratosis, acanthosis, and papillomatosis. They may appear to be somewhat streaky; may be tan, brown, or dark brown; and are generally well-circumscribed, papular, pebbly lesions.[3]
  • Lipomas, whether invasive or well circumscribed, are made up of benign-appearing, mature adipocytes. Lipomas in Proteus syndrome tend to not be encapsulated and can lead to local invasion, most often occurring with lesions located in or on the thorax or abdomen.[3] Even lesions that clinically resemble lipomas may not just contain fatty components, and pathologic findings range from simple lipomas to more complex lipohamartomas.[13]
  • Vascular malformations are of the single-channel type, with capillaries, venules, lymphatics, or combinations of these noted within the lesions. They tend to be lined with flat epithelium and growth tends to mirror the patient’s own somatic growth; however, unlike sporadic vascular lesions that may regress over time, this seldom, if ever, occurs in patients with Proteus syndrome.[1] To add to the confusion, vascular lesions in Proteus syndrome frequently contain lymphatic elements and are therefore sometimes classified as lymphatic malformations or lymphovenous malformations.[13]
  • Tissue resected from enlarged digits generally has a hamartomatous appearance with less organized connective tissue elements; hyaline cartilaginous nodules may also be seen.[13]
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Contributor Information and Disclosures
Author

Beth A Pletcher, MD  Associate Professor, Co-Director of The Neurofibromatosis Center of New Jersey, Department of Pediatrics, University of Medicine and Dentistry of New Jersey

Beth A Pletcher, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, American Medical Association, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Elaine H Zackai, MD  Professor of Pediatrics, Professor of Obstetrics and Gynecology, Professor of Pediatrics in Human Genetics, University of Pennsylvania School of Medicine; Director, Clinical Genetics Center, University of Pennsylvania; Senior Physician and Director of Clinical Genetics, The Children's Hospital of Philadelphia

Elaine H Zackai, MD is a member of the following medical societies: American Cleft Palate/Craniofacial Association, American College of Medical Genetics, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

Robert Anthony Saul, MD  Clinical Professor, Department of Pediatrics, University of South Carolina; Senior Clinical Geneticist, Greenwood Genetic Center

Robert Anthony Saul, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, and American College of Physician Executives

Disclosure: Nothing to disclose.

Daniel Rauch, MD, FAAP  Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine

Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine

Disclosure: Baxter Honoraria Consulting

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

References

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Macroglossia and hemifacial overgrowth associated with hyperpigmentation.
Port wine stain on the trunk with small epidermal nevus.
Macrodactyly with splaying of toes after toe reduction procedure.
Ear enlargement associated with cutaneous hyperpigmentation and hemifacial macrosomia.
Scoliosis with scar resulting from prior surgical resection of a large subcutaneous lipoma.
Evidence of proximal muscle wasting of the upper extremities.
Hypertrophy of the thighs and calves.
Profile demonstrating retrognathia.
 
 
 
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