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MCID: PK3004
MIFTS: 24

Pik3ca-Related Overgrowth Spectrum

Categories: Cardiovascular diseases, Fetal diseases, Neuronal diseases, Rare diseases
Genes Variations Related diseases Publications Drugs
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Aliases & Classifications for Pik3ca-Related Overgrowth Spectrum

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MalaCards integrated aliases for Pik3ca-Related Overgrowth Spectrum:

Name: Pik3ca-Related Overgrowth Spectrum 20
Pik3ca Related Overgrowth Spectrum 29 6 17
Pik3ca-Associated Segmental Overgrowth 20

Classifications:

MalaCards categories:
Global: Rare diseases Fetal diseases
Anatomical: Neuronal diseases Cardiovascular diseases
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Summaries for Pik3ca-Related Overgrowth Spectrum

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GARD : 20 PIK3CA -related overgrowth spectrum (PROS) is a group of rare disorders that cause overgrowth of parts of the body, due to mutations in the PIK3CA gene. Specific disorders in this spectrum include: Fibroadipose hyperplasia (also called fibroadipose overgrowth) CLOVES syndrome Megalencephaly-capillary malformation syndrome (MCAP syndrome ) Hemihyperplasia-multiple lipomatosis syndrome (HHML syndrome) Hemimegalencephaly Facial infiltrating lipomatosis (a congenital disorder that causes overgrowth of one side of the face) Signs and symptoms of PROS depend on the specific disorder present. Depending on the disorder, they can include having a larger-than-normal brain ( megalencephaly ), low muscle tone ( hypotonia ), seizures, intellectual disability, changes in the blood vessels ( vascular system), and overgrowth of one area of the body (focal overgrowth) or of multiple areas of the body (segmental overgrowth), with normal growth elsewhere. PROS is usually caused by somatic mutations in the PIK3CA gene. These changes typically are only present in some cells or some areas of the body (called mosaicism), and are not known to be inherited. Rarely, PROS is caused by a de novo germline mutation, which is present in all cells of the body. The diagnosis of a PROS disorder can be confirmed with genetic testing of the PIK3CA gene. Treatment for a PROS disorder may involve surgical interventions, special education, and speech and physical therapies.

MalaCards based summary : Pik3ca-Related Overgrowth Spectrum, also known as pik3ca related overgrowth spectrum, is related to klippel-trenaunay-weber syndrome and megalencephaly-capillary malformation-polymicrogyria syndrome. An important gene associated with Pik3ca-Related Overgrowth Spectrum is PIK3CA (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha). The drugs Clotrimazole and Miconazole have been mentioned in the context of this disorder.

Wikipedia : 73 PIK3CA-related overgrowth spectrum (PROS) is an umbrella term for rare syndromes characterized by... more...

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Related Diseases for Pik3ca-Related Overgrowth Spectrum

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Diseases in the Overgrowth Syndrome family:

Eed-Related Overgrowth Ezh2-Related Overgrowth
Pik3ca-Related Overgrowth Spectrum Pik3ca-Related Overgrowth Syndrome

Diseases related to Pik3ca-Related Overgrowth Spectrum via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 29)
# Related Disease Score Top Affiliating Genes
1 klippel-trenaunay-weber syndrome 11.3
2 megalencephaly-capillary malformation-polymicrogyria syndrome 11.3
3 facial infiltrating lipomatosis 11.3
4 overgrowth syndrome 10.8
5 pik3ca-related overgrowth syndrome 10.7
6 macrocephaly/megalencephaly syndrome, autosomal recessive 10.5
7 megalencephaly 10.5
8 congenital lipomatous overgrowth, vascular malformations, and epidermal nevi 10.5
9 scoliosis 10.4
10 lipomatosis 10.4
11 macrodactyly 10.4
12 hemihyperplasia-multiple lipomatosis syndrome 10.4
13 proteus syndrome 10.3
14 polymicrogyria with or without vascular-type ehlers-danlos syndrome 10.2
15 polymicrogyria 10.2
16 hypertelorism 10.1
17 megalencephaly, autosomal dominant 10.1
18 cowden syndrome 1 10.1
19 nevus, epidermal 10.1
20 capillary malformation-arteriovenous malformation 1 10.1
21 thrombosis 10.1
22 monocular esotropia 10.1
23 diaphragmatic eventration 10.1
24 lymphangioma 10.1
25 cowden syndrome 10.1
26 polyhydramnios 10.1
27 esotropia 10.1
28 hemimegalencephaly 10.1
29 isolated megalencephaly 10.1

Graphical network of the top 20 diseases related to Pik3ca-Related Overgrowth Spectrum:



Diseases related to Pik3ca-Related Overgrowth Spectrum
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Symptoms & Phenotypes for Pik3ca-Related Overgrowth Spectrum

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Drugs & Therapeutics for Pik3ca-Related Overgrowth Spectrum

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Drugs for Pik3ca-Related Overgrowth Spectrum (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 9)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Clotrimazole Approved, Vet_approved Phase 2 23593-75-1 2812
2
Miconazole Approved, Investigational, Vet_approved Phase 2 22916-47-8 4189
3
Sirolimus Approved, Investigational Phase 2 53123-88-9 6436030 5284616
4 Antibiotics, Antitubercular Phase 2
5 Immunosuppressive Agents Phase 2
6 Immunologic Factors Phase 2
7 Anti-Bacterial Agents Phase 2
8 Anti-Infective Agents Phase 2
9 Antifungal Agents Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Nonrandomized Open Label Pilot Study of Sirolimus Therapy for Segmental Overgrowth Caused by Somatic PI3K Activation Completed NCT02428296 Phase 2 Sirolimus
2 A Phase 1/2 Study of ARQ 092 (Miransertib) in Subjects With PIK3CA-related Overgrowth Spectrum (PROS) and Proteus Syndrome (PS) (MOSAIC) Active, not recruiting NCT03094832 Phase 1, Phase 2 Miransertib
3 EPIK-P2: A Phase II Double-blind Study With an Upfront, 16-week Randomized, Placebo-controlled Period, to Assess the Efficacy, Safety and Pharmacokinetics of Alpelisib (BYL719) in Pediatric and Adult Patients With PIK3CA-related Overgrowth Spectrum (PROS) Not yet recruiting NCT04589650 Phase 2 Alpelisib;Placebo
4 Retrospective Chart Review Study of Patients With PIK3CA-Related Overgrowth Spectrum (PROS) Who Have Received Alpelisib as Part of a Compassionate Use Program (EPIK-P1) Recruiting NCT04285723
5 Managed Access Program (MAP) to Provide Alpelisib (BYL719) for Patients With PIK3CA-Related Overgrowth Spectrum (PROS) Available NCT04085653 alpelisib

Search NIH Clinical Center for Pik3ca-Related Overgrowth Spectrum

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Genetic Tests for Pik3ca-Related Overgrowth Spectrum

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Genetic tests related to Pik3ca-Related Overgrowth Spectrum:

# Genetic test Affiliating Genes
1 Pik3ca Related Overgrowth Spectrum 29
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Anatomical Context for Pik3ca-Related Overgrowth Spectrum

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Publications for Pik3ca-Related Overgrowth Spectrum

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Articles related to Pik3ca-Related Overgrowth Spectrum:

(show top 50) (show all 69)
# Title Authors PMID Year
1
Molecular diagnosis of PIK3CA-related overgrowth spectrum (PROS) in 162 patients and recommendations for genetic testing. 61 6
28151489 2017
2
Alpelisib Plus Fulvestrant in PIK3CA-Altered and PIK3CA-Wild-Type Estrogen Receptor-Positive Advanced Breast Cancer: A Phase 1b Clinical Trial. 6
30543347 2019
3
Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development. 6
28425981 2017
4
CLOVES syndrome: review of a PIK3CA-related overgrowth spectrum (PROS). 20 61
27426476 2017
5
PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution. 6
27631024 2016
6
Mammalian target of rapamycin pathway mutations cause hemimegalencephaly and focal cortical dysplasia. 6
25599672 2015
7
De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. 6
22729224 2012
8
Multiple oncogenic mutations and clonal relationship in spatially distinct benign human epidermal tumors. 6
21078999 2010
9
Functional analysis of PIK3CA gene mutations in human colorectal cancer. 6
15930273 2005
10
Genes and phenotypes in vascular malformations. 61
33368487 2021
11
Cerebellar dysplasia related to PIK3CA mutation: a three-case series. 61
32901329 2021
12
Segmental Ipsilateral Odontognathic Dysplasia (Mandibular Involvement in Segmental Odontomaxillary Dysplasia?) and Identification of PIK3CA Somatic Variant in Lesional Mandibular Gingival Tissue. 61
32500425 2021
13
Clinical experience with the AKT1 inhibitor miransertib in two children with PIK3CA-related overgrowth syndrome. 61
33639990 2021
14
Custom Pediatric Oncology Next-Generation Sequencing Panel Identifies Somatic Mosaicism in Archival Tissue and Enhances Targeted Clinical Care. 61
33221597 2021
15
Lipoblastoma phenotype contains a somatic PIK3CA mutation. 61
33034408 2021
16
Evolution over Time of Leg Length Discrepancy in Patients with Syndromic and Isolated Lateralized Overgrowth. 61
33465347 2021
17
Prenatal imaging diagnosis of PIK3CA-related overgrowth spectrum disorders in first trimester with emphasis on extremities. 61
31816130 2020
18
Congenital infiltrating lipomatosis of the face with lingual mucosal neuromas associated with a PIK3CA mutation. 61
32770747 2020
19
Neutralization of HSF1 in cells from PIK3CA-related overgrowth spectrum patients blocks abnormal proliferation. 61
32620236 2020
20
Detailed analysis of phenotypes and genotypes in megalencephaly-capillary malformation-polymicrogyria syndrome caused by somatic mosaicism of PIK3CA mutations. 61
32778138 2020
21
PIK3CA vascular overgrowth syndromes: an update. 61
32692051 2020
22
Diffuse capillary malformation with overgrowth contains somatic PIK3CA variants. 61
31909475 2020
23
Novel features of PIK3CA-Related Overgrowth Spectrum: Lesson from an aborted fetus presenting a de novo constitutional PIK3CA mutation. 61
31568861 2020
24
PIK3CA mutations in lipomatosis of nerve with or without nerve territory overgrowth. 61
31481664 2020
25
Disorders Caused by Genetic Mosaicism. 61
32181732 2020
26
One of the First Cases with PIK3CA-related Overgrowth Spectrum (PROS) in Saudi Arabia: A Case Report and Literature Review. 61
31929958 2020
27
Alpelisib Treatment for Genital Vascular Malformation in a Patient with Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, and Spinal/Skeletal Anomalies and/or Scoliosis (CLOVES) Syndrome. 61
31330249 2019
28
Vascular malformations syndromes: an update. 61
31693582 2019
29
Thrombosis risk factors in PIK3CA-related overgrowth spectrum and Proteus syndrome. 61
31490637 2019
30
A dyadic genotype-phenotype approach to diagnostic criteria for Proteus syndrome. 61
31692258 2019
31
PI3K/mTOR Pathway Inhibition: Opportunities in Oncology and Rare Genetic Diseases. 61
31752127 2019
32
Early activating somatic PIK3CA mutations promote ectopic muscle development and upper limb overgrowth. 61
30919936 2019
33
Old treatments for new genetic conditions: Sirolimus therapy in a child affected by mosaic overgrowth with fibroadipose hyperplasia. 61
31012097 2019
34
[Syndromes with vascular skin anomalies]. 61
31111168 2019
35
Hormonal receptors in cutaneous vascular malformations: 51 cases. 61
30810814 2019
36
Safety and efficacy of low-dose sirolimus in the PIK3CA-related overgrowth spectrum. 61
30270358 2019
37
Molecular diagnosis of somatic overgrowth conditions: A single-center experience. 61
30761771 2019
38
Insights into the pathogenesis of macrodactyly. 61
30086673 2019
39
Segmental epidermal nevus and mucosal neuromas associated with PIK3CA-related overgrowth spectrum disorder. 61
30511004 2018
40
Characterization of a severe case of PIK3CA-related overgrowth at autopsy by droplet digital polymerase chain reaction and report of PIK3CA sequencing in 22 patients. 61
30063105 2018
41
Cancer-Associated PIK3CA Mutations in Overgrowth Disorders. 61
30197175 2018
42
[New nosological and therapeutic perspectives in syndromic vascular malformations with a vein-lymphatic component]. 61
29627129 2018
43
Urine cell-free DNA is a biomarker for nephroblastomatosis or Wilms tumor in PIK3CA-related overgrowth spectrum (PROS). 61
29300373 2018
44
PIK3CA c.3140A>G mutation in a patient with suspected Proteus Syndrome: a case report. 61
29988677 2018
45
The importance of prenatal 3-dimensional sonography in a case of a segmental overgrowth syndrome with unclear chromosomal microarray results. 61
29023778 2018
46
PIK3CA-related overgrowth spectrum: concurrence of multiple anomalies in one patient. 61
29578286 2018
47
In vitro efficacy of ARQ 092, an allosteric AKT inhibitor, on primary fibroblast cells derived from patients with PIK3CA-related overgrowth spectrum (PROS). 61
29549527 2018
48
Causal somatic mutations in urine DNA from persons with the CLOVES subgroup of the PIK3CA-related overgrowth spectrum. 61
29231959 2018
49
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-related overgrowth spectrum: A brief report. 61
29493003 2018
50
mTOR mutations in Smith-Kingsmore syndrome: Four additional patients and a review. 61
28892148 2018
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Variations for Pik3ca-Related Overgrowth Spectrum

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ClinVar genetic disease variations for Pik3ca-Related Overgrowth Spectrum:

6 (show all 14)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PIK3CA NM_006218.4(PIK3CA):c.1133G>A (p.Cys378Tyr) SNV Pathogenic 39704 rs397514565 GRCh37: 3:178922364-178922364
GRCh38: 3:179204576-179204576
2 PIK3CA NM_006218.4(PIK3CA):c.3129G>T (p.Met1043Ile) SNV Pathogenic 217292 rs121913283 GRCh37: 3:178952074-178952074
GRCh38: 3:179234286-179234286
3 PIK3CA NM_006218.4(PIK3CA):c.2727C>A (p.Phe909Leu) SNV Pathogenic 995381 GRCh37: 3:178947852-178947852
GRCh38: 3:179230064-179230064
4 PIK3CA NM_006218.4(PIK3CA):c.325GAA[1] (p.Glu110del) Microsatellite Pathogenic 995382 GRCh37: 3:178916938-178916940
GRCh38: 3:179199150-179199152
5 PIK3CA NM_006218.4(PIK3CA):c.271G>A (p.Asp91Asn) SNV Pathogenic 995383 GRCh37: 3:178916884-178916884
GRCh38: 3:179199096-179199096
6 PIK3CA NM_006218.4(PIK3CA):c.3129G>A (p.Met1043Ile) SNV Pathogenic 179173 rs121913283 GRCh37: 3:178952074-178952074
GRCh38: 3:179234286-179234286
7 PIK3CA NM_006218.4(PIK3CA):c.1635G>T (p.Glu545Asp) SNV Pathogenic 217293 rs121913275 GRCh37: 3:178936093-178936093
GRCh38: 3:179218305-179218305
8 PIK3CA NM_006218.4(PIK3CA):c.3140A>T (p.His1047Leu) SNV Pathogenic 13653 rs121913279 GRCh37: 3:178952085-178952085
GRCh38: 3:179234297-179234297
9 PIK3CA NM_006218.4(PIK3CA):c.3140A>G (p.His1047Arg) SNV Pathogenic 13652 rs121913279 GRCh37: 3:178952085-178952085
GRCh38: 3:179234297-179234297
10 PIK3CA NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) SNV Pathogenic 13655 rs104886003 GRCh37: 3:178936091-178936091
GRCh38: 3:179218303-179218303
11 PIK3CA NM_006218.4(PIK3CA):c.1258T>C (p.Cys420Arg) SNV Pathogenic 31945 rs121913272 GRCh37: 3:178927980-178927980
GRCh38: 3:179210192-179210192
12 PIK3CA NM_006218.4(PIK3CA):c.1636C>A (p.Gln546Lys) SNV Likely pathogenic 13657 rs121913286 GRCh37: 3:178936094-178936094
GRCh38: 3:179218306-179218306
13 PIK3CA NM_006218.4(PIK3CA):c.311C>T (p.Pro104Leu) SNV Likely pathogenic 217291 rs863225060 GRCh37: 3:178916924-178916924
GRCh38: 3:179199136-179199136
14 PIK3CA NM_006218.4(PIK3CA):c.407dup (p.Gln137fs) Duplication Likely pathogenic 587630 rs1560137609 GRCh37: 3:178917531-178917532
GRCh38: 3:179199743-179199744
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Expression for Pik3ca-Related Overgrowth Spectrum

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Search GEO for disease gene expression data for Pik3ca-Related Overgrowth Spectrum.
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Pathways for Pik3ca-Related Overgrowth Spectrum

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GO Terms for Pik3ca-Related Overgrowth Spectrum

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Sources for Pik3ca-Related Overgrowth Spectrum

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3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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