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PIK3CA related overgrowth syndrome

MedGen UID:
1790024
Concept ID:
C4728213
Disease or Syndrome
Synonyms: PIK3CA related overgrowth spectrum; PIK3CA-associated segmental overgrowth; PIK3CA-Related Segmental Overgrowth
SNOMED CT: PROS - phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha related overgrowth spectrum (737037004); Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha related overgrowth syndrome (737037004); PIK3CA related overgrowth syndrome (737037004)
 
Orphanet: ORPHA530313

Disease characteristics

Excerpted from the GeneReview: PIK3CA-Related Overgrowth Spectrum
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. 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 (e.g., MCAP [megalencephaly-capillary malformation] syndrome and CLOVES [congenital lipomatous asymmetric overgrowth of the trunk, lymphatic, capillary, venous, and combined-type vascular malformations, epidermal nevi, skeletal and spinal anomalies] syndrome). The predominant areas of overgrowth include the brain, limbs (including fingers and toes), trunk (including abdomen and chest), and face, all usually in an asymmetric distribution. Generalized brain overgrowth may be accompanied by secondary overgrowth of specific brain structures resulting in ventriculomegaly, a markedly thick corpus callosum, and cerebellar tonsillar ectopia with crowding of the posterior fossa. Vascular malformations may include capillary, venous, and less frequently, arterial or mixed (capillary-lymphatic-venous or arteriovenous) malformations. Lymphatic malformations may be in various locations (internal and/or external) and can cause various clinical issues, including swelling, pain, and occasionally localized bleeding secondary to trauma. Lipomatous overgrowth may occur ipsilateral or contralateral to a vascular malformation, if present. The degree of intellectual disability appears to be mostly related to the presence and severity of seizures, cortical dysplasia (e.g., polymicrogyria), and hydrocephalus. Many children have feeding difficulties that are often multifactorial in nature. Endocrine issues affect a small number of individuals and most commonly include hypoglycemia (largely hypoinsulinemic hypoketotic hypoglycemia), hypothyroidism, and growth hormone deficiency. [from GeneReviews]
Authors:
Ghayda Mirzaa  |  John M Graham  |  Kim Keppler-Noreuil   view full author information

Professional guidelines

PubMed

Schönewolf-Greulich B, Karstensen HG, Hjortshøj TD, Jørgensen FS, Harder KM, Frevert S, Hove H, Diness BR
Eur J Med Genet 2022 Oct;65(10):104590. Epub 2022 Aug 11 doi: 10.1016/j.ejmg.2022.104590. PMID: 35964931

Recent clinical studies

Etiology

Triana P, Sarmiento MDC, Rodriguez-Laguna L, Martinez-Glez V, Lopez-Gutierrez JC
Ann Vasc Surg 2023 Jan;88:233-238. Epub 2022 Jul 22 doi: 10.1016/j.avsg.2022.06.097. PMID: 35878698
Schönewolf-Greulich B, Karstensen HG, Hjortshøj TD, Jørgensen FS, Harder KM, Frevert S, Hove H, Diness BR
Eur J Med Genet 2022 Oct;65(10):104590. Epub 2022 Aug 11 doi: 10.1016/j.ejmg.2022.104590. PMID: 35964931
Forde K, Resta N, Ranieri C, Rea D, Kubassova O, Hinton M, Andrews KA, Semple R, Irvine AD, Dvorakova V
Orphanet J Rare Dis 2021 Feb 27;16(1):109. doi: 10.1186/s13023-021-01745-0. PMID: 33639990Free PMC Article
Boccara O, Galmiche-Rolland L, Dadone-Montaudié B, Ariche-Maman S, Coulet F, Eyries M, Pannier S, Soupre V, Molina T, Pedeutour F, Fraitag S
Histopathology 2020 Mar;76(4):540-549. Epub 2020 Jan 24 doi: 10.1111/his.14021. PMID: 31630434

Diagnosis

Cohen-Cutler S, Blatt J, Bayliff S, Iacobas I, Hammill A, Sisk BA
J Pediatr 2023 Oct;261:113579. Epub 2023 Jun 22 doi: 10.1016/j.jpeds.2023.113579. PMID: 37353145
Triana P, Sarmiento MDC, Rodriguez-Laguna L, Martinez-Glez V, Lopez-Gutierrez JC
Ann Vasc Surg 2023 Jan;88:233-238. Epub 2022 Jul 22 doi: 10.1016/j.avsg.2022.06.097. PMID: 35878698
Schönewolf-Greulich B, Karstensen HG, Hjortshøj TD, Jørgensen FS, Harder KM, Frevert S, Hove H, Diness BR
Eur J Med Genet 2022 Oct;65(10):104590. Epub 2022 Aug 11 doi: 10.1016/j.ejmg.2022.104590. PMID: 35964931
Harnarayan P, Harnanan D
Vasc Health Risk Manag 2022;18:201-209. Epub 2022 Apr 2 doi: 10.2147/VHRM.S358849. PMID: 35401004Free PMC Article
Brouillard P, Schlögel MJ, Homayun Sepehr N, Helaers R, Queisser A, Fastré E, Boutry S, Schmitz S, Clapuyt P, Hammer F, Dompmartin A, Weitz-Tuoretmaa A, Laranne J, Pasquesoone L, Vilain C, Boon LM, Vikkula M
Orphanet J Rare Dis 2021 Jun 10;16(1):267. doi: 10.1186/s13023-021-01898-y. PMID: 34112235Free PMC Article

Therapy

Kim YM, Lee Y, Choi Y, Choi IH, Heo SH, Choi JM, Do HS, Jang JH, Yum MS, Yoo HW, Lee BH
BMC Med Genomics 2022 Sep 30;15(1):206. doi: 10.1186/s12920-022-01362-1. PMID: 36175890Free PMC Article
Garreta Fontelles G, Pardo Pastor J, Grande Moreillo C
Br J Clin Pharmacol 2022 Aug;88(8):3891-3895. Epub 2022 Feb 21 doi: 10.1111/bcp.15270. PMID: 35146800
Forde K, Resta N, Ranieri C, Rea D, Kubassova O, Hinton M, Andrews KA, Semple R, Irvine AD, Dvorakova V
Orphanet J Rare Dis 2021 Feb 27;16(1):109. doi: 10.1186/s13023-021-01745-0. PMID: 33639990Free PMC Article
Venot Q, Blanc T, Rabia SH, Berteloot L, Ladraa S, Duong JP, Blanc E, Johnson SC, Hoguin C, Boccara O, Sarnacki S, Boddaert N, Pannier S, Martinez F, Magassa S, Yamaguchi J, Knebelmann B, Merville P, Grenier N, Joly D, Cormier-Daire V, Michot C, Bole-Feysot C, Picard A, Soupre V, Lyonnet S, Sadoine J, Slimani L, Chaussain C, Laroche-Raynaud C, Guibaud L, Broissand C, Amiel J, Legendre C, Terzi F, Canaud G
Nature 2018 Jun;558(7711):540-546. Epub 2018 Jun 13 doi: 10.1038/s41586-018-0217-9. PMID: 29899452Free PMC Article

Clinical prediction guides

Schönewolf-Greulich B, Karstensen HG, Hjortshøj TD, Jørgensen FS, Harder KM, Frevert S, Hove H, Diness BR
Eur J Med Genet 2022 Oct;65(10):104590. Epub 2022 Aug 11 doi: 10.1016/j.ejmg.2022.104590. PMID: 35964931
Forde K, Resta N, Ranieri C, Rea D, Kubassova O, Hinton M, Andrews KA, Semple R, Irvine AD, Dvorakova V
Orphanet J Rare Dis 2021 Feb 27;16(1):109. doi: 10.1186/s13023-021-01745-0. PMID: 33639990Free PMC Article
Boccara O, Galmiche-Rolland L, Dadone-Montaudié B, Ariche-Maman S, Coulet F, Eyries M, Pannier S, Soupre V, Molina T, Pedeutour F, Fraitag S
Histopathology 2020 Mar;76(4):540-549. Epub 2020 Jan 24 doi: 10.1111/his.14021. PMID: 31630434

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