Diagnosis

Diagnosing PROS (PIK3CA-Related Overgrowth Spectrum) early is important for ongoing assessment and care

Proper diagnosis of PROS can help guide assessment and care by the appropriate specialists. A multidisciplinary health care team is often necessary to manage all affected organs and potential complications.1 There is a potential for misdiagnosis of PROS due to clinical overlap with other overgrowth disorders (eg, Proteus syndrome, PTEN hamartoma tumor syndrome, type II segmental Cowden syndrome, Neurofibromatosis type 1, or Epidermal nevus syndrome).2

 

The diagnosis of PROS may include clinical assessment, imaging, observation of onset timing, and genomic testing

 

National Institutes of Health (NIH) Workshop Diagnostic Criteria2*

 

Congenital or early childhood onset

Sporadic and mosaic overgrowth

2 or more spectrum features OR  any 1 isolated feature

Spectrum features (2 or more)

  • Overgrowth: adipose, muscle, nerve, skeletal
  • Epidermal nevus
  • Vascular malformations: capillary, venous, arteriovenous, lymphatic
 

Isolated features (any 1)

  • Large, isolated lymphatic malformation
  • Truncal adipose overgrowth
  • Benign lichenoid keratoses
  • Seborrheic keratoses
  • HME (bilateral)/DMEG/focal cortical dysplasia type ll
  • Isolated macrodactyly or overgrown, splayed feet/hands, overgrown limbs
  • Epidermal nevus

Presence of a somatic PIK3CA mutation

 
  • Due to the mosaic nature of PIK3CA mutations in PROS, genomic testing may not always reveal the presence of a PIK3CA mutation2
  • Detection of a PIK3CA mutation depends on the degree of overgrowth, as well as the distribution and amount of detectable mutation in the tissue2
  • Technical limitations, sample availability, and difficulties with interpreting the results may impact the decision to test1-3

A presumptive PROS diagnosis can be considered based on features if a PIK3CA mutation is not identified1-3

 

Have additional questions about diagnosing PROS?

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*Clinical diagnostic criteria were determined after a 2-day workshop that included several researchers who have been studying this group of disorders and 3 parent representatives of patient-family support and advocacy organizations for individuals with these conditions. These criteria may change as research develops.2
A presumptive PROS diagnosis can be considered based on features if a PIK3CA mutation is not identified.1-3
DMEG, dysplastic megalencephaly; HME, hemimegalencephaly.

 

References:
  1. Kang HC, Baek ST, Song S, Gleeson JG. Clinical and genetic aspects of the segmental overgrowth spectrum due to somatic mutations in PIK3CA. J Pediatr. 2015;167(5):957-962.
  2. Keppler-Noreuil KM, Rios JJ, Parker VER, et al. PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation. Am J Med Genet A. 2015;167A(2):287-295.
  3. Kuentz P, St-Onge J, Duffourd Y, et al. Molecular diagnosis of PIK3CA-related overgrowth spectrum (PROS) in 162 patients and recommendations for genetic testing. Genet Med. 2017;19(9):989-997.