Gain of function mutations of the PIK3CA gene are known to be associated with a spectrum of childhood onset phenotypes including the following:

Disorders of predominantly brain involvement:

  • The megalencephaly-capillary malformation syndrome (MCAP)
  • Dysplastic megalencephaly (DMEG)
  • Focal cortical dysplasia (FCD)
  • Hemimegalencephaly (HMEG)
  • Megalencephaly with autism (rare)

Disorders of predominantly body (non-brain) involvement:

  • CLOVES syndrome
  • Klippel-Trenaunay syndrome
  • Infiltrating facial lipomatosis
  • Lymphatic malformations (can be isolated)
  • Vascular malformations (including capillary or venous malformations, can be isolated)
  • Focal overgrowth phenotypes (e.g. isolated macrodactyly)
  • Other diverse single tissue phenotypes (e.g. epidermal nevi)

A growing number of children are now known to have overlapping features of both brain and body overgrowth phenotypes. The term “PIK3CA related somatic overgrowth” (or PROS) has now become increasingly used to encompass these phenotypes.