Patient Impact Overview

Patients with PIK3CA-Related Overgrowth Spectrum (PROS) can experience disfiguring, function-limiting, and life-threatening effects¹

For many patients with PROS, overgrowth is sizable and highly visible. For others, however, it may take less overt forms, like vascular malformation. Regardless, PROS can significantly compromise the functional capabilities of even very young patients and can cause life-threatening complications.^2-5 Although survival data have not been reported reliably, early mortality has been observed in case reports.^5,6

Specific complications of PROS^2-4,7

For more information about the complications that patients with PROS experience, click here.

The psychosocial effects of PROS are wide ranging, but they can impact quality of life for some patients^8-17

The medical complications of PROS can compromise quality of life and social functioning in patients of all ages, although effects can vary considerably from one patient to the next.⁸

Pain and limited mobility have been reported in patients with PROS, including those with KTS, macrodactyly, CLOVES syndrome, MCAP or M-CM, FAO, and vascular malformations. Functional issues range in severity. Some patients find walking and exercising difficult; others may find themselves wheelchair bound.^8-15

Some patients, like those with KTS and vascular malformations, see their disorders affect their mental health and ability to form interpersonal relationships. Studies of patients with KTS have found increased stress, anxiety, depression, sleep disturbances, and general lower quality-of-life scores. Young patients may miss school, have trouble building relationships, and experience bullying.^8,9 Adult patients have commonly reported difficulty at work and financial stress.⁸ Patients with neurological involvement, like those with MCAP or M-CM, may also suffer from developmental and cognitive delays.¹⁰

It's important to remember that each PROS disorder comes with its own range of severity and signs and symptoms. Learn more about these differences here.

Despite the differences in the signs and symptoms that patients with PROS may experience, these psychosocial challenges highlight an additional complexity in care that may require the attention of additional specialists.¹⁸

CLOVES, congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal and spinal; FAO, fibroadipose hyperplasia or overgrowth; KTS, Klippel-Trenaunay syndrome; MCAP or M-CM, megalencephaly-capillary malformation.

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.
2. Parker VER, Keppler-Noreuil KM, Faivre L, et al. Genet Med. 2019;21(5):1189-1198.
3. 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(7):1713-1733.
4. 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.
5. Sapp JC, Turner JT, van de Kamp JM, van Dijk FS, Lowrey RB, Biesecker LG. Newly delineated syndrome of congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE syndrome) in seven patients. Am J Med Genet A. 2007;143A(24):2944-2958.
6. Emrick LT, Murphy L, Shamshirsaz AA, et al. Prenatal diagnosis of CLOVES syndrome confirmed by detection of a mosaic PIK3CA mutation in cultured amniocytes. Am J Med Genet A. 2014:164A(10):2633-2637.
7. 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.
8. Harvey JA, Nguyen H, Anderson KR, et al. Pain, psychiatric comorbidities, and psychosocial stressors associated with Klippel-Trenaunay syndrome. J Am Acad Dermatol. 2018;79(5):899-903.
9. 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.
10. Mirzaa GM, Conway RL, Gripp KW, et al. Megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH) syndromes: two closely related disorders of brain overgrowth and abnormal brain and body morphogenesis. Am J Med Genet A. 2012;158A(2):269-291.
11. Oduber CEU, Klemlani K, Sillevis Smitt JH, Hennekam RCM, van der Horst CM. Baseline Quality of Life in patients with Klippel-Trenaunay syndrome. J Plast Reconstr Aesthet Surg. 2010;63(4):603-609.
12. Breugem CC, Merkus MP, Smitt JH, Legemate DA, van der Horst CM. Quality of life in patients with vascular malformations of the lower extremity. Br J Plast Surg. 2004;57(8):754-763.
13. Fahrni JO, Cho EY, Engelberger RP, Baumgartner I, von Känel R. Quality of life in patients with congenital vascular malformations. J Vasc Surg Venous Lymphat Disord. 2014;2(1):46-51.
14. Cappuccio G, Alagia M, D’Anna M, et al. Gait disturbance and lower limb pain in a patient with PIK3CA-related disorder. Eur J Med Genet. 2017;60(12):655-657.
15. Keppler-Noreuil KM, Sapp JC, Lindhurst MJ, et al. Clinical delineation and natural history of the PIK3CA-related overgrowth spectrum. Supplementary appendix. Am J Med Genet A. 2014;164A(7):1713-1733.
16. Hagen SL, Grey KR, Korta DZ, Kelly KM. Quality of life in adults with facial port-wine stains. J Am Acad Dermatol. 2017;76(4):695-702.
17. Lanigan SW, Cotterill JA. Psychological disabilities amongst patients with port wine stains. Br J Dermatol. 1989;121(2):209-215.
18. Lindeke LL, Leonard BJ, Presler B, Garwick A. Family-centered care coordination for children with special needs across multiple settings. J Pediatr Health Care. 2002;16(6):290-297.