Diagnostic Criteria

PIK3CA-related overgrowth spectrum (PROS) encompasses a range of clinical findings in which the core features are congenital or early-childhood onset of segmental/focal overgrowth with or without cellular dysplasia in the absence of a family history of similarly affected individuals (i.e., single occurrence in a family). Prior to the identification of PIK3CA as the causative gene, PROS was separated into distinct clinical syndromes based on the tissues and/or organs involved .

Suggestive Findings

PROS should be considered in individuals with the following clinical, brain MRI, and family history findings .

Clinical features

Source: GeneReviews — "PIK3CA-Related Overgrowth Spectrum"

Differential Diagnosis

A number of overgrowth and megalencephaly disorders overlap with the PIK3CA-related overgrowth spectrum (PROS), including those summarized in . Table 4. Genes of Interest in the Differential Diagnosis of PIK3CA-Related Overgrowth Spectrum (PROS)

Management Guidelines

Clinical practice guidelines for PIK3CA-related overgrowth spectrum have been published (full text). Additionally, a targeted pharmacologic therapy has been FDA approved .

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual with PIK3CA-related overgrowth spectrum (PROS), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Note: Assessment is complicated by variable findings in individuals with this condition. Accurate and thorough assessment of medical history is necessary to evaluate for vascular malformations as well as other clinical features.

Table 5.

Recommended Evaluations Following Initial Diagnosis in Individuals with PIK3CA-Related Overgrowth Spectrum

System/Concern | Evaluation | Comment

Constitutional

(overgrowth) | Measure growth parameters incl head circumference, total body length, length of arms, hands, legs feet. | To assess for generalized segmental overgrowth (incl leg length discrepancy) macrocephaly

Consider whole-body MRI. | In those w/truncal overgrowth

Consider limb radiographs subsequent limb MRI. | In those w/segmental or generalized overgrowth of a limb

Consider spinal ultrasound in infants spinal MRI (w/MR angiography) in older persons. | In those w/evidence of spinal involvement (See also Cardiovascular/Vascular in this table.)

Clinical assessment for pain functional impairment |

Constitutional

(undergrowth

or generalized

growth

Source: GeneReviews — "PIK3CA-Related Overgrowth Spectrum"

Surveillance Guidelines

Table 8. Recommended Surveillance for Individuals with PIK3CA-Related Overgrowth Spectrum

Source: GeneReviews — "PIK3CA-Related Overgrowth Spectrum"