PIK3CA

Management

Medical management largely depends on the disorder or set of features caused by PIK3CA mutations. Some of the most common medical management guidelines include:

Surveillance

  • Baseline brain and spinal cord imaging, especially in children with neurological involvement (e.g. macrocephaly, epilepsy, neurodevelopmental delays) for early detection of cortical dysplasia, ventriculomegaly, and cerebellar tonsillar ectopia.
  • A cardiovascular assessment including a baseline echocardiogram and electrocardiogram to evaluate for cardiovascular malformations and rhythm abnormalities
  • A baseline renal ultrasound to evaluate for structural renal abnormalities
  • Surgical and orthopedic referrals for individuals suspected of having CLOVES syndrome or fibroadipose hyperplasia, and individuals with MCAP syndrome with focal somatic overgrowth or leg-length discrepancy.
  • Evaluation by appropriate specialists for children with isolated vascular or lymphatic malformations.

Management of neurologic and neurosurgical manifestations

  • Neurosurgical referral and management are warranted for individuals with hydrocephalus, progressive or symptomatic cerebellar tonsillar ectopia (CBTE) or Chiari malformation.
  • Focal cortical dysplasia, hemimegalencephaly and polymicrogyria are associated with increased risk for epilepsy. Treatment considerations for epilepsy include standard anti-epileptic drugs (AEDs), the ketogenic diet, and surgical resection (for focal lesions in particular).

Management of somatic manifestations

  • Somatic overgrowth phenotypes, vascular, lymphatic and musculoskeletal manifestations due to PIK3CA mutations require individualized, often multi-disciplinary, medical management. Prompt diagnosis (by MR/CT and angiography) is warranted. Most individuals undergo (often several) debulking or orthopedic procedures with significant complications.
  • In classic CLOVES, truncal lipomatous mass infiltrates surrounding tissues and often requires surgical excision.
  • Severe scoliosis, large truncal mass, paraspinal high-flow lesions with spinal cord ischemia, lymphatic malformations, cutaneous vesicles, orthopedic problems of the feet and hands, and central phlebectasia/thromboembolism are examples of significant morbidities that need active or prophylactic medical intervention.

The use of PI3K-AKT-MTOR pathway inhibitors (including Sirolimus) is now rapidly being explored in PIK3CA related disorders for several indications.