Genetics of Proteus Syndrome Treatment & Management

The mainstays of treatment for Proteus syndrome include early identification of serious medical problems and the use of prophylactic and symptomatic treatment.

• Hemihyperplasia

  • Medical approaches are limited and should be considered in the context of functional improvement.
  • Leg length discrepancy can create a host of secondary morbidities and needs to be addressed by an experienced orthopedist.
  • Macrodactyly can make it difficult for the patient to write, hold objects, dress, eat, or find comfortable footwear.
• Hemifacial macrosomia or macroglossia

  • These present cosmetic concerns and may affect dental occlusion and mastication.
  • Augment routine dental and orthodontic care with a maxillofacial surgeon or craniofacial team consultation as indicated.
• Scoliosis: Early recognition may permit nonsurgical attempts to halt progression.
• Cutaneous and subcutaneous lesions: Periodic evaluation is essential since lipomas and vascular malformations may have local or even systemic effects.
• Cutaneous vascular markings and malformations: Laser treatment is useful for removing cutaneous vascular markings and malformations, such as port wine stains and capillary hemangiomas. It is not yet effective for permanently removing café au lait spots or melanin-related hyperpigmentation.
• Although consistently successful way to treat epidermal nevi has been established, individual reports have noted success with various approaches such as CO ₂ or ruby lasers, dermatome excision followed by phenol peel, cryotherapy, keratolytics, and even intralesional steroid injection.^[14]
• Secondary thrombocytopenia: This may be indicated by a history of easy bruising or presence of petechiae.
• Thrombosis: Aggressive management of thrombosis may be lifesaving in patients who present with calf or leg pain, a palpable cord, and shortness of breath or respiratory distress. Physicians who care for individuals with Proteus syndrome should be made aware of the potential thrombotic risks; hematologic evaluation prior to elective surgery should also be considered.^[3]
• Internal lesions: MRIs of the chest and abdomen can reveal internal lesions such as lipomas or pulmonary cysts. Undetected, these can cause very serious problems before becoming symptomatic.

• Preoperative coagulation studies may provide guidance for perioperative and postoperative management of patients with Proteus syndrome. Some clinicians have suggested serious consideration of prophylactic anticoagulation prior to elective surgery; however, this decision must be made on an individual basis while exploring the risks and benefits and in the context of the patient’s clinical circumstances (including laboratory studies and the anticipated surgery).^[9]
• Progressive scoliosis may require orthopedic intervention.
• Exceptionally large digits may require surgical reduction or even amputation in extreme circumstances so that the patient can wear shoes or use their hand.
• Hemifacial macrosomia or macroglossia may require surgical intervention if airway obstruction, feeding difficulties, or severe malocclusion is present. These complex situations often require a coordinated, multidisciplinary team approach with input from a craniofacial surgeon, orthodontist, and dentist.
• Although any competent surgeon can resect large or invasive cutaneous or subcutaneous lesions, plastic surgical consultation is advisable for cosmetically important areas such as the face. Subcutaneous lesions impinging on vital structures, obstructing vision, or growing rapidly deserve immediate attention. Laser lipolysis using a 980-nm laser diode is a more recent addition to the treatment armamentarium and has been used successfully in a child to reduce the size of a large lipomatous lesion.^[15] This approach may be shown in the future to have advantages over surgical excision or liposuction for specific types of lesions.
• Internal lipomas or cystic lung malformations may also require surgical resection.

• An orthopedist is a vital team member who must address the functional significance of both hemihyperplasia and scoliosis.
• A craniofacial surgeon or surgical team can address cranial asymmetry or hemifacial macrosomia.
• A general or plastic surgeon can address resection of cutaneous or subcutaneous lesions when necessary.
• A neurosurgeon can address CNS lesions such as cortical overgrowth, with or without hydrocephalus. Patients undergoing complex craniofacial procedures can also benefit from a neurosurgeon's operative expertise.
• A dermatologist can evaluate and monitor subcutaneous and cutaneous lesions and can perform biopsies when necessary.
• An ophthalmologist can closely monitor strabismus or orbital asymmetry in a patient with ocular involvement.
• A dentist can address dental anomalies and an orthodontist can treat malocclusion.
• A geneticist and genetic counselor can provide the patient and family with additional information about the diagnosis, diagnostic testing, proposed genetic mechanisms, and recurrence risks. Family planning options and prenatal diagnosis are also addressed in this clinical setting.
• A developmental pediatrician can evaluate a child with learning disabilities or developmental delays. This specialist makes recommendations for ongoing therapy and school interventions.
• A psychologist or trained mental health professional can assist a child or adolescent with significant disfigurement, if adjustment problems arise. Social stigmatization is a major obstacle for many children and adults. Both patients and family members may benefit from ongoing psychotherapy. Clinicians should be especially aware of how parents of affected children are coping and should consider referral for psychological support as needed. Peer support for affected older teens and adults is available from the Proteus Syndrome Organization.^[16]

• In the absence of surgery, encourage patients to participate in all activities as fully as possible.
• Patients who undergo spinal fusion or other major surgical procedures need to confer with their surgeons about acceptable activities.