Laboratory Studies
AKT1 testing should be offered to patients suspected of having Proteus syndrome. A punch biopsy of affected tissue is ideal, but a skin scraping of epidermal nevi has been noted to be effective. [16] Because the mutation is somatic, peripheral blood testing is not high yield in diagnosis.
Platelet studies 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).
Imaging Studies
See the list below:
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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.
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MRI or CT scanning [15]
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. [17]
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. [17] Postprocessing CT densitovolumetry may also help to more clearly delineate the extent of cystic lung involvement in patients with pulmonary manifestations. [18]
Multidetector CT with intravenous contrast may be used to identify a PE when this becomes a clinical concern. [17]
Other Tests
See the list below:
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Electroencephalography is indicated for any patient with a history or symptoms suggesting seizures.
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Pulmonary function tests may help evaluate patients with respiratory symptoms.
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Venograms, Doppler studies, or ventilation/perfusion (V/Q) studies may be helpful diagnostic tools in patients with symptoms suggestive of DVT or PE.
Histologic Findings
See the list below:
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Connective tissue nevi resemble tightly compacted, collagen-rich connective tissue.
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Epidermal nevi generally exhibit a combination of hyperkeratosis, parakeratosis, acanthosis, and papillomatosis. Clinically they may appear to be somewhat streaky; may be tan, brown, or dark brown; and are generally well-circumscribed, papular, pebbly lesions. [5]
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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. [5] Even lesions that clinically resemble lipomas may not just contain fatty components, and pathologic findings range from simple lipomas to more complex lipohamartomas. [19]
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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. 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. [19]
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Tissue resected from enlarged digits generally has a hamartomatous appearance with less organized connective tissue elements; hyaline cartilaginous nodules may also be seen. [19]
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Macroglossia and hemifacial overgrowth associated with hyperpigmentation.
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Port wine stain on the trunk with small epidermal nevus.
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Macrodactyly with splaying of toes after toe reduction procedure.
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Ear enlargement associated with cutaneous hyperpigmentation and hemifacial macrosomia.
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Scoliosis with scar resulting from prior surgical resection of a large subcutaneous lipoma.
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Evidence of proximal muscle wasting of the upper extremities.
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Hypertrophy of the thighs and calves.
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Profile demonstrating retrognathia.
