Table 7.

Supportive Treatment of Manifestations in Individuals with PIK3CA-Related Overgrowth Spectrum

May require debulking surgeryIf functional limitations or pain are moderate to severe
Leg length
Standard treatment per orthopedistMay require a shoe lift if length discrepancy >2 cm
Standard treatment per neurosurgeon; may incl ventriculoperitoneal shunting or 3rd ventriculostomy
  • If signs & symptoms of obstructive hydrocephalus or ↑ intracranial pressure
  • Hydrocephalus may be more successfully treated in those w/MCAP via a 3rd ventriculostomy [Author, personal observation].
Cerebellar tonsillar
ectopia or Chiari
Standard treatment per neurosurgeon; may incl a posterior fossa decompression
  • If signs & symptoms of cerebellar ectopia or syringomyelia 1, 2
  • Many affected persons have mild cerebellar tonsillar ectopia that may only require monitoring (see Surveillance).
Epilepsy 3 Standardized treatment w/ASM by experienced neurologist or epileptologist
  • Many ASMs may be effective; none has been demonstrated effective specifically for this disorder
  • Education of parents/caregivers 4
Consideration of hemispherectomy or surgical resection of the epileptic focus 5In those w/focal or supportive findings by neuroimaging, EEG, or clinical semiology of the seizure disorder
DD/ID See Developmental Delay / Intellectual Disability Management Issues.
Standard treatment per psychiatrist &/or developmental pediatricianSee Social/Behavioral Concerns.
Polydactyly Consider removal of extra digits.Per orthopedist
Foot deformities /
Splayed toes
Surgical intervention may be considered; per orthopedistTo allow for shoes & improved function
Scoliosis Standard treatment per orthopedist
Depending on type of vascular malformations: sclerotherapy, laser therapy, or oral medications (e.g., sirolimus)
Structural heart
defects / Arrhythmia
Standard treatment per cardiologist
Standard treatment per vascular anomalies teamMay incl careful surgical debulking or oral medications (See Therapies Under Investigation.)
Lipomas Careful surgical debulking of infiltrative masses, typically requiring multidisciplinary mgmt 6Paraspinal & intraspinal extension pose significant risk for compression of the cord, thecal sac, & nerve roots.
Renal anomalies /
Standard treatment per urologist &/or nephrologist
Wilms tumor Standard treatment per oncologist
Coagulopathy or
Standard treatment per hematologist depending on the coagulation issue; may incl anticoagulant therapy for thrombosis or fresh frozen plasma infusion for coagulopathyThose w/CLOVES phenotype are at particular risk of developing a postoperative hypercoagulable state → thrombosis.
Pain Evaluate for source of pain & treat underlying cause, e.g., vascular malformation, secondary effects of overgrowth (nerve impingement, compression of internal organs), or functional impairments.
Hypothyroidism Standard treatment per endocrinologistMore likely in those w/MCAP or other forms of PROS that incl brain involvement 7
  • Depending on severity, treatment can range from infusion of IV glucose to administration of sugar-containing drinks or snacks to cornstarch therapy.
  • In some instances of persistent hypoglycemia, glucagon injections may be considered.
  • Primarily affects neonates, though some persons may develop hypoglycemia later in life.
  • In severe, persistent hypoglycemia, eval of the GH axis & HPA axis is indicated.
If hypoglycemia is due to growth hormone deficiency, consideration of GH therapyLimited data re efficacy of GH therapy & whether it is contraindicated in this population.
Growth hormone
Consider a trial of GH therapy. 7
  • Undertake careful follow up of linear growth & trajectory of overgrowth.
  • Delay of GH therapy until after age 2 yrs has been suggested, avoiding the major period of brain growth.
  • Further evidence is needed to determine relative risks & benefits of GH therapy in GH-deficient persons w/PROS. 7
  • Ensure appropriate social work involvement to connect families w/local resources, respite, & support.
  • Coordinate care to manage multiple subspecialty appointments, equipment, medications, & supplies.
  • Ongoing assessment of need for palliative care involvement &/or home nursing
  • Consider involvement in adaptive sports or Special Olympics.

ASM = anti-seizure medication; DD/ID = developmental delay / intellectual disability; GH = growth hormone; HPA = hypothalamic-pituitary-adrenal; OT = occupational therapy; PT = physical therapy


Infants may have irritability, excessive drooling, difficulty swallowing, or breathing problems, especially central apnea.


Children may have neck pain or headache, motor weakness, sensory changes, vision problems, swallowing difficulties, or behavioral changes.


The severity of epilepsy varies depending on the nature and extent of cortical malformations, type of PIK3CA pathogenic variant, and level of mosaicism.


Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy see Epilepsy Foundation Toolbox.


From: PIK3CA-Related Overgrowth Spectrum

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