Diagnostic Criteria
Consensus clinical diagnostic criteria for Proteus syndrome (PS) have been published . Suggestive Findings PS should be suspected in a proband with the following: • Distorting, progressive overgrowth, typically of postnatal onset, often resulting in asymmetric distortion of the skeletal architecture. Hemimegencephaly can be prenatal. • Cerebriform connective tissue nevi characterized by deep grooves and gyrations as seen on the surface of the brain • Linear verrucous epidermal nevus, a streaky, pigmented, rough nevus that often follows the lines of Blaschko and can be present anywhere on the body • Adipose dysregulation, including lipomatous overgrowth and lipoatrophy • Vascular malformations, including cutaneous capillary malformations, prominent venous patterning or varicosities, and lymphatic malformations • Overgrowth of other tissues, most commonly spleen, liver, thymus, and gastrointestinal tract • Tumors, most commonly meningiomas. Ovarian cystadenomas, breast cancer, parotid monomorphic adenoma, mesothelioma, and others have also been reported. • Bullous pulmonary degeneration • Dysmorphic facial features including dolichocephaly, long face, downslanting palpebral fissures, and/or minor ptosis, depressed nasal bridge, wide or anteverted nares, and open mouth at rest Establishing the Diagnosis The diagnosis of PS is established in a proband with ALL of the following three general criteria: • Mosaic distribution of lesions • Sporadic occurrence • Progressive course AND using the following positive (and negative) clinical criteria : • A score of ≥10 points in an individual with a mosaic AKT1 pathogenic variant • A score of ≥15 points in an individual without a mosaic AKT1 pathogenic variant* Note: The diagnosis of is established in an individual with a mosaic AKT1 pathogenic variant and a score of 2-9 using clinical criteria. *Individuals without a mosaic AKT1 pathogenic variant should be considered to have PS, not AKT1-related Proteus syndrome (AKT1-PS). However, the clinical criteria were intended to diagnose PS with confidence based only on clinical criteria, and individuals with these clinical criteria should be managed the same as those with AKT1-PS. Table 1. Positive and Negative Clinical Criteria Used in the Diagnosis of Proteus Syndrome Positive Clinical Criteria | Points Cerebriform connective tissue nevus | 5
Asymmetric, disproportionate overgrowth(of ≥1 of the following): | Limbs |
|---|
Megaspondylodysplasia, scoliosis, or rib hyperostosis Organ/visceral overgrowth(of ≥2 of the following): | Central nervous system |
2 Dysregulated adipose tissue(incl ≥1 of the following): | Lipomas |
2 Vascular malformations(incl ≥1 of the following): | Capillary malformation |
Lymphatic malformation Specific tumors(incl ≥1 of the following): | Female genitourinary cystadenoma (age 11 yrs) |
Testicular cystadenomas or cystadenocarcinomas Facial phenotype(≥3 features) | Dolichocephaly |
Source: GeneReviews — "Proteus Syndrome"
