Proteus Syndrome

Excerpt

Clinical characteristics: Proteus syndrome (PS) is characterized by progressive segmental or patchy overgrowth most commonly affecting the skeleton, skin, adipose, and central nervous systems. In most individuals PS has modest or no manifestations at birth, develops and progresses rapidly beginning in the toddler period, and relentlessly progresses through childhood, causing severe overgrowth and disfigurement. It is associated with a range of tumors, pulmonary complications, and a striking predisposition to deep vein thrombosis and pulmonary embolism.

Diagnosis/testing: The diagnosis of PS is established in a proband with all three general criteria (mosaic distribution of lesions, sporadic occurrence, progressive course) and a clinical score based on positive and negative criteria of at least ten points in an individual with a mosaic AKT1 pathogenic variant or at least 15 points in an individual without a mosaic AKT1 pathogenic variant identified by molecular genetic testing. The diagnosis of AKT1-related overgrowth spectrum is established in an individual with a mosaic AKT1 pathogenic variant and a clinical score of 2-9.

Management: Treatment of manifestations: Management of overgrowth including orthopedic procedures to delay or halt linear bone growth; rehabilitation medicine care including physical and occupational therapy; correction of skeletal deformities such as scoliosis; dermatologic management of the skin manifestations, especially the cerebriform connective tissue nevi with pedorthic intervention as needed; surgery as needed for lipomatous overgrowth; evaluation and treatment of deep vein thrombosis and pulmonary embolism; treatment of tumors per surgeon and/or oncologist; treatment of bullous pulmonary disease per pulmonologist; developmental intervention and/or special education for developmental delays; psychosocial counseling is warranted in most individuals.

Surveillance: Monitoring should be tailored to individual presentation. Orthopedic, rehabilitation medicine, physical therapy, occupational therapy, pulmonary, dermatology, and developmental evaluations as needed; routine monitoring for evidence of tumor development is by medical history and physical examination; periodic imaging is not indicated.

Agents/circumstances to avoid: Medications that increase the risk of deep vein thrombosis or are procoagulant; medications that increase growth (e.g., androgenic steroids, growth hormone).

Genetic counseling: PS and AKT1-related overgrowth spectrum are not inherited: there are no confirmed occurrences of vertical transmission or sib recurrence. There is no known risk to offspring of an affected individual; however, the number of affected individuals who have reproduced is very small. Thus, the risks to the parents of an affected child and to affected persons who do reproduce are not increased compared to the general population. Because PS and AKT1-related overgrowth spectrum are not inherited, prenatal testing is not indicated.