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PROS Disorders

Not actual patients.

PIK3CA-Related Overgrowth Spectrum (PROS) is a spectrum of diverse overgrowth disorders caused by a PIK3CA mutation1

Features of PROS disorders broadly include the following types of overgrowth:

Lipomatous overgrowth, vascular malformations, skeletal overgrowth, lymphatic malformations

Despite the range of presentation, PROS disorders have clinical commonalities1

Clinical hallmarks of PROS include congenital or early childhood onset, sporadic and mosaic overgrowth, and a progressive course of disease.

PROS and its associated overgrowth can have a substantial effect on patients’ lives2,3

Patients with PROS experience a variety of signs and symptoms related to their disorders. These manifestations can cause severe medical complications, disfigurements, and functional complications that interfere with daily living.

Bone abnormalities icon

Bone abnormalities, including leg asymmetry and scoliosis

 

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Pain

 

Hypertrophy icon

Hypertrophy

 

Vascular complications icon

Vascular complications, including disseminated intravascular coagulation

 

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Fatigue

 

The effects of overgrowth can add to the already severe burden on quality of life from PROS signs and symptoms.3-6 To manage the effects of PROS, patients may require repeat surgeries, interventional procedures, and extensive care.7,8

Disorders now recognized to be part of PROS include1,7,9,10:

  1. KTS (Klippel-Trenaunay Syndrome)

  2. CLOVES syndrome (Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevi, Scoliosis/skeletal and spinal)

  3. ILM (Isolated Lymphatic Malformation)

  4. MCAP (or M-CM) (Megalencephaly-Capillary Malformation)

  5. HME (HemiMegalEncephaly)/DMEG (Dysplastic MEGalencephaly)/Focal cortical dysplasia type II

  6. HHML (HemiHyperplasia-Multiple Lipomatosis)

  7. FIL (Facial Infiltrating Lipomatosis)

  8. FAVA (FibroAdipose Vascular Anomaly)

  9. Macrodactyly

  10. Muscular HH (HemiHyperplasia)

  11. FAO (FibroAdipose hyperplasia or Overgrowth)

  12. CLAPO syndrome (Capillary malformation of the lower lip, Lymphatic malformation of the face and neck, Asymmetry of the face and limbs, and Partial or generalized Overgrowth)

  13. Epidermal nevus, benign lichenoid keratosis, or seborrheic keratosis

+Other disorders may be identified and characterized as PROS

Explore the journeys of 3 patients with PROS
References: 
1. 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. doi:10.1002/ajmg.a.36836
2. Jacob AG, Driscoll DJ, Shaughnessy WJ, Stanson AW, Clay RP, Gloviczki P. Klippel-Trénaunay syndrome: spectrum and management. Mayo Clin Proc. 1998;73(1):28-36. doi:10.1016/S0025-6196(11)63615-X
3. van der Ploeg HM, van der Ploeg MN, van der Ploeg-Stapert JD. Psychological aspects of the Klippel-Trenaunay syndrome. J Psychosom Res. 1995;39(2):183-191. doi:10.1016/0022-3999(94)00096-n
4. Zhang J, Wang K, Mei J. Late puerperal hemorrhage of a patient with Klippel-Trenaunay syndrome: a case report. Medicine (Baltimore). 2019;98(50):e18378. doi:10.1097/MD.0000000000018378
5. Keppler-Noreuil KM, Sapp JC, Lindhurst MJ, et al. Clinical delineation and natural history of the PIK3CA-related overgrowth spectrum. Am J Med Genet A. 2014;164A(suppl):1-47. doi:10.1002/ajmg.a.36552
6. Alomari AI, Chaudry G, Rodesch G, et al. Complex spinal-paraspinal fast-flow lesions in CLOVES syndrome: analysis of clinical and imaging findings in 6 patients. Am J Neuroradiol. 2011;32(10):1812-1817. doi:10.3174/ajnr.A2349
7. Bertino F, Braithwaite KA, Hawkins CM, et al. Congenital limb overgrowth syndromes associated with vascular anomalies. Radiographics. 2019;39(2):491-515. doi:10.1148/rg.2019180136
8. Bessis D, Vernhet H, Bigorre M, Quéré I, Rössler J. Life-threatening cutaneous bleeding in childhood Klippel-Trenaunay syndrome treated with oral sirolimus. JAMA Dermatol. 2016;152(9):1058-1059. doi:10.1001/jamadermatol.2016.1008
9. Rodriguez-Laguna L, Ibañez K, Gordo G, et al. CLAPO syndrome: identification of somatic activating PIK3CA mutations and delineation of the natural history and phenotype. Genet Med. 2018;20(8):882-889. doi:10.1038/gim.2017.200
10. Alomari AI, Spencer SA, Arnold RW, et al. Fibro-Adipose Vascular Anomaly: Clinical-Radiologic-Pathologic Features of a Newly Delineated Disorder of the Extremity. J Pediatr Orthop. 2014;34(1):109–117. doi: 10.1097/BPO.0b013e3182a1f0b8.