History
In cases of suspected Proteus syndrome, clinicians must carefully use the standard diagnostic criteria (as listed below) to preclude misdiagnosis. These criteria can guide the decision to order AKT1 testing.
The following are the 3 general criteria necessary for clinical diagnosis without regard to specific clinical features (when patients meet the strict clinical criteria, there is a >90% positive predictive value in the genetic testing):
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Lesions follow a mosaic distribution or pattern
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Problems follow a progressive course
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The disorder appears to be sporadic (ie, not inherited)
Diagnostic confirmation also requires the presence of findings from category A, B, or C.
Category A
Connective tissue nevus is required.
Category B
Two of the following are required:
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Epidermal nevus
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Disproportionate overgrowth of one or more of the following: limbs, digits, cranium, vertebrae, external auditory meatus, spleen, or thymus
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Bilateral ovarian cystadenomas or a parotid monomorphic adenoma in a patient younger than 20 years
Category C
All three of the following are required:
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Lipomas or focal atrophy of adipose tissue
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Capillary, venous, or lymphatic malformation or lung bullae
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Facial features including dolichocephaly, a long face, down - slanting palpebrae, ptosis, depressed nasal bridge, anteverted nares, and open mouth position while at rest
Physical
The following are characteristics of Proteus syndrome:
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When present at birth, asymmetric limb, digital, or cranial overgrowth may be a major diagnostic finding
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Digital, limb, or cranial overgrowth usually involves both soft tissue and bone
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Cranial or external auditory canal hyperostosis may be seen
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Scoliosis associated with disproportionate vertebral growth is common
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The combination of disproportionate overgrowth and focal atrophy can lead to a unique habitus characterized by wasting of upper arm muscles, an elongated thorax, an extremely gracile neck, and muscular hypertrophy of the thighs
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Cystic lung malformations that lead to cystic pulmonary emphysema and restrictive lung disease secondary to severe scoliosis are relatively common; recurrent pneumonias, shortness of breath, or reduced exercise tolerance may point to significant respiratory compromise
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Organomegaly is less common but can also occur with splenomegaly or occasional thymus enlargement
Cutaneous findings include the following:
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The 6 most common skin findings include (from most to least frequent) lipomas, vascular malformations, connective tissue nevi, epidermal nevi, partial lipohypoplasia, and patchy dermal hypoplasia
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Connective tissue nevi are virtually pathognomonic and typically have a cerebriform contour; they often occur on the soles of the feet but can also be found on other areas
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Epidermal nevi tend to be the flat, soft variety
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Lipomas may be well demarcated or locally invasive, with large intra-abdominal or intrathoracic lesions presenting serious medical concerns
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Vascular lesions may include capillaries, lymphatics, venules, or combinations of these; they tend to grow gradually over time and, unlike the more common capillary hemangiomas seen in the general population, rarely regress; port wine stains or patchy hyperpigmentation may also be seen
Facial features that often coincide with poor mental development include a prominent occiput, ptosis with or without down - slanting palpebrae, upturned nose, and a long, narrow face.
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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.
