Proteus Syndrome

Proteus syndrome is a rare condition in which there is excessive growth of a portion of the body. There may be no evidence of the condition at birth; instead, it becomes apparent between 6-18 months of age and becomes more severe with age. Proteus syndrome is not an inherited condition and is characterized by various cutaneous and subcutaneous lesions, including vascular malformations, lipomas, hyperpigmentation and several types of nevi. Cerebriform nevi are thought to be characteristic of the disorder.

The following have been noted in patients with Proteus syndrome:

• Hemi hypertrophy
• Abnormal fat distribution
• Absent or decreased subcutaneous fat-wasting syndrome
• Facial involvement, which may be associated with asymmetric mandibular growth, maxillary growth, or both, as well as with premature dental eruption and idiopathic root resorption
• Eye conditions such as strabismus or epibulbar dermoids or cysts
• Scoliosis or kyphoscoliosis
• Kidney or bladder problems, though these are less common
• Cutaneous and subcutaneous lesions:
  • Lipomas
  • Connective tissue nevi and epidermal nevi
  • Vascular malformations
• Ovarian cystadenomas
• Cystic lung malformations
• Intrathoracic or intra-abdominal lipomas
• Coagulopathies
• Learning disabilities or developmental delays

Proteus syndrome is caused by a mutation in the AKT1 gene. This is a condition that arises randomly during the early stages of fetal development.

Diagnosis:

You/your child will meet with the Vascular Anomalies Center team during the initial clinic visit for a comprehensive review of the patient’s medical history, any imaging studies and/or laboratory tests that have been performed, and a complete physical examination. The medical specialists will then confer and diagnose the condition and propose a treatment plan. Diagnosis is primarily based on the physical examination.

There are three general characteristics or features that must be present to consider a diagnosis of Proteus syndrome:

1. Mosaic distribution: Areas of overgrowth are patchy and that only some body parts show signs of overgrowth while others are unaffected.
2. Sporadic occurrence: No one else in the affected person’s family has similar features of overgrowth.
3. Progressive course: The overgrowth has noticeably altered the appearance of the affected body parts over time or that new areas of overgrowth have appeared over time.

A diagnosis of Proteus syndrome requires all three general features to be present and either one feature from category A, two features from category B or three features from category C, as shown below.

Category A

• Cerebriform connective tissue nevus

Category B

• Linear epidermal nevus
• Asymmetric, disproportionate overgrowth
• Specific tumors before being 20 years old of age
• Bilateral ovarian cystadenoma
• Parotid monomorphic adenoma

Category C

• Abnormal growth and/or distribution of fat
  • Fatty tumors (lipomas)
  • Lack of fat under the skin (regional lipohypoplasia)
• Vascular malformations
• Lung cysts
• Specific facial features:
  • A long and narrow head (dolichocephaly)
  • Long face
  • Down slanting palpebral fissures and/or minor dropping of the eyelids (ptosis)
  • Depressed nasal bridge
  • Wide or opening nares
  • Open mouth at rest

Treatment:

There is no cure for Proteus syndrome and individualized treatment is focused on symptoms that the child is experiencing.Patients with Proteus syndrome are followed by several specialists. These specialists may include:

• Orthopedic surgeons who will address overgrowth and provide procedures to delay or stop linear bone growth and correction of skeletal deformities
• General surgeons
• Plastic reconstructive surgeons
• Interventional radiologists
• Hematologists who will monitor and treat any blood clotting issues
• Oncologists who would monitor any tumor development
• Dermatologists to monitor skin lesions
• Physical/occupational therapists
• Cognitive/education therapists if delays are present