PROTEUSS
MCID: PRT008
MIFTS: 64

Proteus Syndrome (PROTEUSS)

Categories: Bone diseases, Cardiovascular diseases, Fetal diseases, Genetic diseases, Infectious diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Proteus Syndrome

MalaCards integrated aliases for Proteus Syndrome:

Name: Proteus Syndrome 56 12 74 24 52 25 58 73 36 29 54 6 43 15 71
Partial Gigantism-Nevi-Hemihypertrophy-Macrocephaly Syndrome 52 58
Proteus Syndrome, Somatic 56 13
Gigantism, Partial, of Hands and Feet, Nevi, Hemihypertrophy, and Macrocephaly 56
Partial Gigantism of Hands and Feet Nevi Hemihypertrophy and Macrocephaly 73
Partial Gigantism of Hands and Feet, Nevi, Hemihypertrophy, Macrocephaly 52
Hemihypertrophy and Macrocephaly 52
Syndrome, Proteus, Somatic 39
Wiedemann's Syndrome 12
Proteuss 73
Ps 25

Characteristics:

Orphanet epidemiological data:

58
proteus syndrome
Inheritance: Not applicable; Prevalence: <1/1000000 (Europe); Age of onset: Infancy; Age of death: any age;

OMIM:

56
Inheritance:
somatic mutation

Miscellaneous:
onset in infancy
progressive disorder
sporadic occurrence
mosaic distribution of lesions


HPO:

31
proteus syndrome:
Inheritance somatic mutation sporadic
Onset and clinical course infantile onset progressive


GeneReviews:

24
Penetrance Incomplete penetrance cannot be assessed in a mosaic genetic disorder that is not inherited.

Classifications:

Orphanet: 58  
Rare neurological diseases
Rare circulatory system diseases
Rare bone diseases
Rare skin diseases
Developmental anomalies during embryogenesis


Summaries for Proteus Syndrome

Genetics Home Reference : 25 Proteus syndrome is a rare condition characterized by overgrowth of the bones, skin, and other tissues. Organs and tissues affected by the disease grow out of proportion to the rest of the body. The overgrowth is usually asymmetric, which means it affects the right and left sides of the body differently. Newborns with Proteus syndrome have few or no signs of the condition. Overgrowth becomes apparent between the ages of 6 and 18 months and gets more severe with age. In people with Proteus syndrome, the pattern of overgrowth varies greatly but can affect almost any part of the body. Bones in the limbs, skull, and spine are often affected. The condition can also cause a variety of skin growths, particularly a thick, raised, and deeply grooved lesion known as a cerebriform connective tissue nevus. This type of skin growth usually occurs on the soles of the feet and is hardly ever seen in conditions other than Proteus syndrome. Blood vessels (vascular tissue) and fat (adipose tissue) can also grow abnormally in Proteus syndrome. Some people with Proteus syndrome have neurological abnormalities, including intellectual disability, seizures, and vision loss. Affected individuals may also have distinctive facial features such as a long face, outside corners of the eyes that point downward (down-slanting palpebral fissures), a low nasal bridge with wide nostrils, and an open-mouth expression. For reasons that are unclear, affected people with neurological symptoms are more likely to have distinctive facial features than those without neurological symptoms. It is unclear how these signs and symptoms are related to abnormal growth. Other potential complications of Proteus syndrome include an increased risk of developing various types of noncancerous (benign) tumors and a type of blood clot called a deep venous thrombosis (DVT). DVTs occur most often in the deep veins of the legs or arms. If these clots travel through the bloodstream, they can lodge in the lungs and cause a life-threatening complication called a pulmonary embolism. Pulmonary embolism is a common cause of death in people with Proteus syndrome.

MalaCards based summary : Proteus Syndrome, also known as partial gigantism-nevi-hemihypertrophy-macrocephaly syndrome, is related to hemimegalencephaly and congenital lipomatous overgrowth, vascular malformations, and epidermal nevi. An important gene associated with Proteus Syndrome is AKT1 (AKT Serine/Threonine Kinase 1), and among its related pathways/superpathways are PI3K-Akt signaling pathway and mTOR signaling pathway. Affiliated tissues include lung, skin and bone, and related phenotypes are scoliosis and kyphosis

Disease Ontology : 12

NIH Rare Diseases : 52 Proteus syndrome is characterized by excessive growth of a part or portion of the body. The overgrowth is usually asymmetric, which means it affects the right and left sides of the body differently. Newborns with Proteus syndrome have few or no signs of the disorder. Overgrowth becomes apparent between the ages of 6 and 18 months and becomes more severe with age. It may result in differences in appearance and with time, an increased risk for blood clots and tumors . Some people with Proteus syndrome have neurological abnormalities, including intellectual disability , seizures , and vision loss, as well as distinctive facial features. Proteus syndrome is caused by a change (mutation ) in the AKT1 gene . It is not inherited , but occurs as a random mutation in a body cell in a developing baby (fetus) early in pregnancy. The AKT1 gene mutation affects only a portion of the body cells. This is why only a portion of the body is affected and why individuals with Proteus syndrome can be very differently affected. Management of the condition often requires a team of specialists with knowledge of the wide array of features and complications of this condition.

OMIM : 56 Proteus syndrome is a highly variable, severe disorder of asymmetric and disproportionate overgrowth of body parts, connective tissue nevi, epidermal nevi, dysregulated adipose tissue, and vascular malformations. Specific features include cerebriform connective tissue nevus, thin limbs, lipomas, and lung cysts. Some patients may have intellectual disability with dysmorphic facies. Deep venous thrombosis is common and constitutes a significant risk factor. Many features of Proteus syndrome overlap with other overgrowth syndromes (Turner et al., 2004; review by Cohen, 2014). Cohen (2014) provided a detailed review of the clinical features, diagnosis, and management issues of Proteus syndrome. Some authors (52,51:Zhou et al., 2000, 2001; Smith et al., 2002) have reported a 'Proteus-like' syndrome associated with germline and tissue-specific somatic mutations in the PTEN gene (601728), which is mutated in Cowden syndrome (CWS1); see 158350 for a discussion of these patients. (176920)

KEGG : 36 Proteus syndrome (PS) is a generally severe but highly variable disorder caused by an activating AKT1 mutation. The diagnosis of PS requires fulfillment of three general criteria: sporadic occurrence, mosaic distribution of lesions, and a progressive course in addition to various specific criteria. These specific manifestations include, but are not limited to, cerebriform connective tissue nevus, linear epidermal nevus, asymmetric, disproportionate overgrowth, dysregulated adipose tissue, vascular malformations, and lung cysts.

UniProtKB/Swiss-Prot : 73 Proteus syndrome: A highly variable, severe disorder of asymmetric and disproportionate overgrowth of body parts, connective tissue nevi, epidermal nevi, dysregulated adipose tissue, and vascular malformations. Many features of Proteus syndrome overlap with other overgrowth syndromes.

Wikipedia : 74 Proteus syndrome is a rare disorder with a genetic background that can cause tissue overgrowth involving... more...

GeneReviews: NBK99495

Related Diseases for Proteus Syndrome

Diseases in the Proteus Syndrome family:

Proteus-Like Syndrome

Diseases related to Proteus Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 474)
# Related Disease Score Top Affiliating Genes
1 hemimegalencephaly 33.0 PIK3CA MTOR AKT3
2 congenital lipomatous overgrowth, vascular malformations, and epidermal nevi 32.9 PROS1 PIK3R2 PIK3CA AKT3 AKT1
3 macrodactyly 31.3 TSC1 PIK3CA
4 lipomatosis 31.2 PTEN PIK3CA FGFR1
5 lipomatosis, multiple 30.9 PTEN NF1 FGFR1
6 hemangioma 30.7 TSC2 PTEN MTOR GNAQ AKT1
7 congenital heart defects, hamartomas of tongue, and polysyndactyly 30.6 TSC2 TSC1 PTEN
8 neurofibromatosis, type iv, of riccardi 30.5 TSC2 PTEN NF1 MTOR AKT1
9 klippel-trenaunay-weber syndrome 30.4 PROS1 PIK3CA GNAQ AKT3 AKT1 AGGF1
10 megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 30.3 PIK3R2 AKT3
11 megalencephaly 30.3 PIK3R2 PIK3CA AKT3
12 polymicrogyria 30.3 PIK3R2 PIK3CA AKT3
13 hydrocephalus 30.3 PTEN PIK3R2 FGFR1 AKT3
14 cowden syndrome 1 30.3 TSC2 TSC1 TNS1 RHEB PTEN PLEK
15 thyroid carcinoma 30.1 PTEN PIK3CA AKT1
16 cowden syndrome 30.1 TSC2 TSC1 TNS1 RHEB PTEN PLEK
17 meningioma, familial 30.0 RHEB PTEN NF1 AKT1
18 glioma 29.8 PTEN PIK3CA NF1 FGFR1 AKT3
19 benign ependymoma 29.8 TSC2 TSC1 NF1 MTOR
20 lymphangioleiomyomatosis 29.5 TSC2 TSC1 MTOR
21 ductal carcinoma in situ 29.5 PTEN PIK3CA AKT1
22 nevus, epidermal 29.1 PTEN PROS1 PIK3R2 PIK3CA NF1 GNAS
23 glioblastoma multiforme 28.3 TSC2 TSC1 PTEN PIK3R2 PIK3CA NF1
24 polydactyly, preaxial ii 11.8
25 proteus-like syndrome 11.7
26 hemihyperplasia, isolated 11.6
27 alzheimer disease 11.5
28 cleft, median, of upper lip with polyps of facial skin and nasal mucosa 11.5
29 scott syndrome 11.4
30 lenz-majewski hyperostotic dwarfism 11.3
31 pfeiffer syndrome 11.2
32 epidermolytic hyperkeratosis 11.2
33 perlman syndrome 11.2
34 progeroid syndrome 11.2
35 premature aging 11.2
36 overgrowth syndrome 10.8
37 thyroid hurthle cell adenoma 10.6 PTEN PIK3CA
38 ovarian clear cell adenofibroma 10.6 PTEN PIK3CA
39 vulvar seborrheic keratosis 10.5 PTEN MTOR
40 gigantism 10.5
41 serous cystadenocarcinoma 10.5 PTEN PIK3CA AKT1
42 cutis marmorata telangiectatica congenita 10.5 PIK3R2 PIK3CA AKT3
43 megalencephaly-capillary malformation-polymicrogyria syndrome 10.5 PIK3R2 PIK3CA AKT3
44 uterine corpus cancer 10.5 PTEN PIK3CA AKT1
45 mixed cell type cancer 10.5 PTEN PIK3CA GPC3
46 scoliosis 10.5
47 oropharynx cancer 10.4 PTEN PIK3CA AKT1
48 respiratory system benign neoplasm 10.4 TSC2 PTEN AKT1
49 testicular germ cell tumor 10.4 PTEN GPC3 AKT1
50 uterine benign neoplasm 10.4 TSC2 PTEN AKT1

Graphical network of the top 20 diseases related to Proteus Syndrome:



Diseases related to Proteus Syndrome

Symptoms & Phenotypes for Proteus Syndrome

Human phenotypes related to Proteus Syndrome:

58 31 (show top 50) (show all 122)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 scoliosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0002650
2 kyphosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0002808
3 skeletal dysplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002652
4 vascular skin abnormality 58 31 hallmark (90%) Very frequent (99-80%) HP:0011276
5 subcutaneous nodule 58 31 hallmark (90%) Very frequent (99-80%) HP:0001482
6 decreased muscle mass 58 31 hallmark (90%) Very frequent (99-80%) HP:0003199
7 abnormal form of the vertebral bodies 58 31 hallmark (90%) Very frequent (99-80%) HP:0003312
8 cachexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0004326
9 arteriovenous malformation 58 31 hallmark (90%) Very frequent (99-80%) HP:0100026
10 melanocytic nevus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000995
11 capillary hemangioma 58 31 hallmark (90%) Very frequent (99-80%) HP:0005306
12 disproportionate tall stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0001519
13 irregular hyperpigmentation 58 31 hallmark (90%) Very frequent (99-80%) HP:0007400
14 lower limb asymmetry 58 31 hallmark (90%) Very frequent (99-80%) HP:0100559
15 lipoma 58 31 hallmark (90%) Very frequent (99-80%) HP:0012032
16 lymphangioma 58 31 hallmark (90%) Very frequent (99-80%) HP:0100764
17 macrodactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0004099
18 upper limb asymmetry 58 31 hallmark (90%) Very frequent (99-80%) HP:0100560
19 asymmetry of the thorax 58 31 hallmark (90%) Very frequent (99-80%) HP:0001555
20 abnormal subcutaneous fat tissue distribution 58 31 hallmark (90%) Very frequent (99-80%) HP:0007552
21 epidermal nevus 58 31 hallmark (90%) Very frequent (99-80%) HP:0010816
22 hypertelorism 58 31 frequent (33%) Frequent (79-30%) HP:0000316
23 finger syndactyly 58 31 frequent (33%) Frequent (79-30%) HP:0006101
24 macrotia 58 31 frequent (33%) Frequent (79-30%) HP:0000400
25 generalized hyperkeratosis 58 31 frequent (33%) Frequent (79-30%) HP:0005595
26 pulmonary embolism 58 31 frequent (33%) Frequent (79-30%) HP:0002204
27 dolichocephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000268
28 lymphedema 58 31 frequent (33%) Frequent (79-30%) HP:0001004
29 visceral angiomatosis 58 31 frequent (33%) Frequent (79-30%) HP:0100761
30 multiple cafe-au-lait spots 58 31 frequent (33%) Frequent (79-30%) HP:0007565
31 round face 58 31 frequent (33%) Frequent (79-30%) HP:0000311
32 calvarial hyperostosis 58 31 frequent (33%) Frequent (79-30%) HP:0004490
33 thrombophlebitis 58 31 frequent (33%) Frequent (79-30%) HP:0004418
34 bronchogenic cyst 58 31 frequent (33%) Frequent (79-30%) HP:0100730
35 abnormal lung lobation 31 frequent (33%) HP:0002101
36 macrocephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000256
37 low-set ears 58 31 occasional (7.5%) Occasional (29-5%) HP:0000369
38 intellectual disability 58 31 occasional (7.5%) Occasional (29-5%) HP:0001249
39 seizures 58 31 occasional (7.5%) Occasional (29-5%) HP:0001250
40 ptosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000508
41 sudden cardiac death 58 31 occasional (7.5%) Occasional (29-5%) HP:0001645
42 cataract 58 31 occasional (7.5%) Occasional (29-5%) HP:0000518
43 splenomegaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0001744
44 depressed nasal bridge 58 31 occasional (7.5%) Occasional (29-5%) HP:0005280
45 macroorchidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000053
46 carious teeth 58 31 occasional (7.5%) Occasional (29-5%) HP:0000670
47 joint stiffness 58 31 occasional (7.5%) Occasional (29-5%) HP:0001387
48 renal cyst 58 31 occasional (7.5%) Occasional (29-5%) HP:0000107
49 downslanted palpebral fissures 58 31 occasional (7.5%) Occasional (29-5%) HP:0000494
50 craniosynostosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001363

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Head:
macrocephaly
dolichocephaly
hyperostoses of calvaria, facial bones, and mandible

Abdomen Spleen:
splenomegaly

Skin Nails Hair Skin Histology:
hyperkeratosis
acanthosis
highly collagenized connective tissue
dermal hypoplasia

Head And Neck Face:
long face

Growth Other:
hemihypertrophy
generalized, unilateral or localized disproportionate overgrowth of any tissue

Cardiovascular Vascular:
capillary malformations
venous malformations
lymphatic malformations
deep vein thrombosis

Skeletal Limbs:
overgrown long bones
thin cortices

Neoplasia:
ovarian cystadenoma
parotid monomorphic adenoma

Head And Neck Eyes:
ptosis
downslanting palpebral fissures
epibulbar dermoids

Head And Neck Mouth:
open mouth

Skeletal Spine:
kyphoscoliosis
megaspondylodysplasia
spinal stenosis from angular kyphoscoliosis

Skin Nails Hair Skin:
lipoma
lymphangioma
hypertrophy of skin of soles
cerebriform connective tissue nevus
lipohypoplasia
more
Head And Neck Nose:
low nasal bridge
wide or anteverted nostrils

Respiratory Lung:
lung cysts

Neurologic Central Nervous System:
brain malformations
spinal cord compression by tumor infiltration
mental retardation, moderate (in some patients)

Clinical features from OMIM:

176920

GenomeRNAi Phenotypes related to Proteus Syndrome according to GeneCards Suite gene sharing:

26 (show all 44)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-2 10.79 PIK3CA MTOR
2 Decreased viability GR00173-A 10.79 PIK3R2
3 Decreased viability GR00221-A-1 10.79 AKT2 AKT3 PIK3R2 AKT1 FGFR1 NF1
4 Decreased viability GR00221-A-2 10.79 AKT3 PIK3R2 TSC1 AKT1 FGFR1 NF1
5 Decreased viability GR00221-A-3 10.79 AKT2 AKT3 TSC1 AKT1
6 Decreased viability GR00221-A-4 10.79 AKT2 AKT3 PIK3R2 AKT1 NF1 PIK3CA
7 Decreased viability GR00301-A 10.79 AKT2 AKT3 PIK3R2 TSC1
8 Decreased viability GR00342-S-1 10.79 MTOR
9 Decreased viability GR00342-S-2 10.79 MTOR
10 Decreased viability GR00342-S-3 10.79 AKT2
11 Decreased viability GR00402-S-2 10.79 AKT2 AKT3 PIK3R2 TSC1 AKT1 FGFR1
12 Increased shRNA abundance (Z-score > 2) GR00366-A-105 10.36 MTOR RHEB
13 Increased shRNA abundance (Z-score > 2) GR00366-A-106 10.36 AKT3
14 Increased shRNA abundance (Z-score > 2) GR00366-A-110 10.36 AKT2
15 Increased shRNA abundance (Z-score > 2) GR00366-A-123 10.36 AKT3
16 Increased shRNA abundance (Z-score > 2) GR00366-A-127 10.36 TSC1
17 Increased shRNA abundance (Z-score > 2) GR00366-A-151 10.36 PTEN
18 Increased shRNA abundance (Z-score > 2) GR00366-A-152 10.36 PTEN
19 Increased shRNA abundance (Z-score > 2) GR00366-A-157 10.36 PIK3CA
20 Increased shRNA abundance (Z-score > 2) GR00366-A-159 10.36 AKT2
21 Increased shRNA abundance (Z-score > 2) GR00366-A-16 10.36 AKT1 MTOR PIK3CA PTEN RHEB
22 Increased shRNA abundance (Z-score > 2) GR00366-A-164 10.36 AKT3
23 Increased shRNA abundance (Z-score > 2) GR00366-A-166 10.36 PIK3CA
24 Increased shRNA abundance (Z-score > 2) GR00366-A-168 10.36 PTEN
25 Increased shRNA abundance (Z-score > 2) GR00366-A-173 10.36 MTOR RHEB
26 Increased shRNA abundance (Z-score > 2) GR00366-A-177 10.36 AKT1 PIK3CA
27 Increased shRNA abundance (Z-score > 2) GR00366-A-190 10.36 PIK3CA
28 Increased shRNA abundance (Z-score > 2) GR00366-A-214 10.36 PTEN
29 Increased shRNA abundance (Z-score > 2) GR00366-A-36 10.36 AKT2
30 Increased shRNA abundance (Z-score > 2) GR00366-A-39 10.36 AKT3
31 Increased shRNA abundance (Z-score > 2) GR00366-A-42 10.36 AKT1 MTOR PIK3CA PTEN RHEB TSC1
32 Increased shRNA abundance (Z-score > 2) GR00366-A-49 10.36 PIK3CA
33 Increased shRNA abundance (Z-score > 2) GR00366-A-50 10.36 AKT1
34 Increased shRNA abundance (Z-score > 2) GR00366-A-52 10.36 AKT3
35 Increased shRNA abundance (Z-score > 2) GR00366-A-57 10.36 RHEB
36 Increased shRNA abundance (Z-score > 2) GR00366-A-60 10.36 AKT1 AKT2 AKT3 MTOR PIK3CA
37 Increased shRNA abundance (Z-score > 2) GR00366-A-63 10.36 PTEN RHEB
38 Increased shRNA abundance (Z-score > 2) GR00366-A-70 10.36 AKT1
39 Increased shRNA abundance (Z-score > 2) GR00366-A-73 10.36 MTOR
40 Increased shRNA abundance (Z-score > 2) GR00366-A-82 10.36 TSC1
41 Increased shRNA abundance (Z-score > 2) GR00366-A-85 10.36 AKT1 AKT2 AKT3 MTOR
42 Increased shRNA abundance (Z-score > 2) GR00366-A-93 10.36 PTEN
43 Decreased cell migration GR00055-A-1 9.91 AKT1 AKT2 AKT3 MTOR NF1 PIK3CA
44 Decreased sensitivity to paclitaxel GR00112-A-0 9.16 NF1 PTEN

MGI Mouse Phenotypes related to Proteus Syndrome:

45 (show all 22)
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.53 AGGF1 AKT1 AKT3 FGFR1 GNAQ GNAS
2 homeostasis/metabolism MP:0005376 10.48 AKT1 AKT2 AKT3 FGFR1 GNAQ GNAS
3 cellular MP:0005384 10.47 AGGF1 AKT1 AKT2 AKT3 FGFR1 GNAS
4 behavior/neurological MP:0005386 10.45 AGGF1 AKT1 AKT3 FGFR1 GNAQ GNAS
5 growth/size/body region MP:0005378 10.44 AKT1 AKT2 AKT3 FGFR1 GNAQ GNAS
6 mortality/aging MP:0010768 10.4 AGGF1 AKT1 AKT2 AKT3 FGFR1 GNAQ
7 hematopoietic system MP:0005397 10.37 AKT1 AKT2 AKT3 FGFR1 GNAQ GNAS
8 embryo MP:0005380 10.36 AGGF1 AKT1 FGFR1 GPC3 MTOR NF1
9 endocrine/exocrine gland MP:0005379 10.35 AKT1 AKT2 AKT3 FGFR1 GNAQ GNAS
10 immune system MP:0005387 10.35 AKT1 AKT2 AKT3 FGFR1 GNAQ GNAS
11 nervous system MP:0003631 10.34 AGGF1 AKT1 AKT2 AKT3 FGFR1 GNAQ
12 integument MP:0010771 10.3 AKT1 AKT2 FGFR1 GNAQ GNAS GPC3
13 muscle MP:0005369 10.29 AKT1 AKT2 FGFR1 GNAQ GNAS MTOR
14 neoplasm MP:0002006 10.2 AGGF1 AKT1 AKT2 AKT3 GNAS NF1
15 normal MP:0002873 10.15 AKT1 AKT2 AKT3 FGFR1 GNAQ GNAS
16 liver/biliary system MP:0005370 10.11 AKT1 AKT2 GNAS NF1 PROS1 PTEN
17 renal/urinary system MP:0005367 9.96 FGFR1 GNAQ GNAS GPC3 MTOR NF1
18 no phenotypic analysis MP:0003012 9.95 AKT2 FGFR1 GNAS LYPD1 MTOR PIK3CA
19 reproductive system MP:0005389 9.9 AKT1 AKT2 AKT3 FGFR1 GPC3 NF1
20 pigmentation MP:0001186 9.72 GNAQ GPC3 NF1 PTEN TSC1
21 respiratory system MP:0005388 9.65 AGGF1 AKT1 AKT2 GNAQ GNAS GPC3
22 skeleton MP:0005390 9.36 AKT1 AKT2 FGFR1 GNAQ GNAS GPC3

Drugs & Therapeutics for Proteus Syndrome

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Phase 1/2 Study of ARQ 092 (Miransertib) in Subjects With PIK3CA-related Overgrowth Spectrum (PROS) and Proteus Syndrome (PS) (MOSAIC) Recruiting NCT03094832 Phase 1, Phase 2 ARQ 092
2 Open Label Phase II Study of Everolimus (RAD001) in Patients With Segmental Overgrowth Syndrome Withdrawn NCT02569125 Phase 2 Everolimus
3 Phase 1 Dose Finding Trial of ARQ 092 in Children and Adults With Proteus Syndrome Active, not recruiting NCT02594215 Phase 1 ARQ 092
4 Informed Consent for Whole Genome Sequencing: Civic Ideals and Social Norms Referenced by Early Participants Completed NCT01369953
5 Positive Exposure: A Photography and Video Intervention for Individuals With Craniofacial Differences Completed NCT00340964
6 The Phenotype and Etiology of Proteus Syndrome and Related Overgrowth Disorders Recruiting NCT00001403
7 Expanded Access to Provide ARQ 092 for the Treatment of Overgrowth Diseases and/or Vascular Anomalies With Genetic Alterations of the PI3K/AKT Pathway Available NCT03317366 ARQ 092

Search NIH Clinical Center for Proteus Syndrome

Cochrane evidence based reviews: proteus syndrome

Genetic Tests for Proteus Syndrome

Genetic tests related to Proteus Syndrome:

# Genetic test Affiliating Genes
1 Proteus Syndrome 29 AKT1

Anatomical Context for Proteus Syndrome

MalaCards organs/tissues related to Proteus Syndrome:

40
Lung, Skin, Bone, Eye, Kidney, Breast, Thymus

Publications for Proteus Syndrome

Articles related to Proteus Syndrome:

(show top 50) (show all 522)
# Title Authors PMID Year
1
A mosaic activating mutation in AKT1 associated with the Proteus syndrome. 61 24 56 6
21793738 2011
2
Reassessment of the Proteus syndrome literature: application of diagnostic criteria to published cases. 61 56 6
15372514 2004
3
Proteus syndrome: diagnostic criteria, differential diagnosis, and patient evaluation. 61 56 6
10360391 1999
4
Sudden death caused by pulmonary thromboembolism in Proteus syndrome. 61 24 56
11140839 2000
5
Clinical differentiation between Proteus syndrome and hemihyperplasia: description of a distinct form of hemihyperplasia. 61 24 56
9781913 1998
6
A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. 24 6
17611497 2007
7
Mutation analysis of the tumor suppressor PTEN and the glypican 3 (GPC3) gene in patients diagnosed with Proteus syndrome. 54 61 56
15372512 2004
8
PTEN mutations are uncommon in Proteus syndrome. 54 61 56
11476065 2001
9
Cutaneous manifestation of lethal genes. 24 56
3957353 1986
10
Proteus syndrome review: molecular, clinical, and pathologic features. 61 56
23992099 2014
11
Proteus Syndrome 61 6
22876373 2012
12
Monozygotic twins discordant for Proteus syndrome. 61 56
18627057 2008
13
Germline mutation of the tumour suppressor PTEN in Proteus syndrome. 61 56
12471211 2002
14
Neonatal Proteus syndrome? 61 56
12244562 2002
15
Lipomatosis of the colon complicating Proteus syndrome. 61 56
11919100 2002
16
Association of germline mutation in the PTEN tumour suppressor gene and Proteus and Proteus-like syndromes. 61 56
11476841 2001
17
Causes of premature death in Proteus syndrome. 61 56
11343327 2001
18
The multifaceted challenges of Proteus syndrome. 61 56
11325326 2001
19
Multiple meningiomas, craniofacial hyperostosis and retinal abnormalities in Proteus syndrome. 61 56
10925389 2000
20
Ocular manifestations in Proteus syndrome. 61 56
10861666 2000
21
Proteus syndrome and immunodeficiency. 61 56
10685928 2000
22
Germline and germline mosaic PTEN mutations associated with a Proteus-like syndrome of hemihypertrophy, lower limb asymmetry, arteriovenous malformations and lipomatosis. 61 56
10749983 2000
23
Elattoproteus syndrome: delineation of an inverse form of Proteus syndrome. 61 56
10213042 1999
24
Non-operative management of a splenic laceration in a patient with the Proteus syndrome. 61 56
9132186 1997
25
Isolated macrodactyly and Proteus syndrome. 61 56
8818455 1996
26
Neoplasms in Proteus syndrome. 61 56
7645604 1995
27
Regional Proteus syndrome and somatic mosaicism. 61 56
8030665 1994
28
Proteus syndrome: clinical evidence for somatic mosaicism and selective review. 61 56
8266991 1993
29
Compromise of the spinal canal in Proteus syndrome. 61 56
8266993 1993
30
Transmission of Proteus syndrome from mother to son? 61 56
8418646 1993
31
Transmission of Proteus syndrome from father to son? 61 56
1770536 1991
32
Pelvic lipomatosis in the Proteus syndrome: a further diagnostic sign. 61 56
2226574 1990
33
The Proteus syndrome: association with nephrogenic diabetes insipidus. 61 56
2208765 1990
34
Proteus syndrome: course of a severe case. 61 56
2309770 1990
35
Proteus syndrome. 61 56
2667470 1989
36
Proteus syndrome versus Bannayan-Zonana syndrome: a problem in differential diagnosis. 61 56
3234431 1988
37
Further diagnostic thoughts about the Elephant Man. 61 56
3135754 1988
38
Cutaneous manifestations of the Proteus syndrome. 61 56
3380758 1988
39
Understanding Proteus syndrome, unmasking the elephant man, and stemming elephant fever. 61 56
3152479 1988
40
Severe proteus syndrome in an 18-month-old boy. 61 56
3605190 1987
41
Proteus syndrome in southern Africa: natural history and clinical manifestations in six individuals. 61 56
3605209 1987
42
Proteus syndrome: an expanded phenotype. 61 56
3605210 1987
43
Lethal genes surviving by mosaicism: a possible explanation for sporadic birth defects involving the skin. 61 56
3033033 1987
44
Proteus syndrome: report of two cases with pelvic lipomatosis. 61 56
4069870 1985
45
Variability in the Proteus syndrome: report of an affected child with progressive lipomatosis. 61 56
3987735 1985
46
Further and new details on the Proteus syndrome. 61 56
6510436 1984
47
The Proteus Syndrome: the emergence of an entity. 61 56
6427414 1984
48
Proteus syndrome. 61 56
6427415 1984
49
The proteus syndrome. Partial gigantism of the hands and/or feet, nevi, hemihypertrophy, subcutaneous tumors, macrocephaly or other skull anomalies and possible accelerated growth and visceral affections. 61 56
6873112 1983
50
Quantifying survival in patients with Proteus syndrome. 61 24
28661492 2017

Variations for Proteus Syndrome

ClinVar genetic disease variations for Proteus Syndrome:

6 ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 AKT1 NM_005163.2(AKT1):c.49_50delinsAG (p.Glu17Arg)indel Pathogenic 800567 14:105246550-105246551 14:104780213-104780214
2 AKT1 NM_005163.2(AKT1):c.49G>A (p.Glu17Lys)SNV Uncertain significance 13983 rs121434592 14:105246551-105246551 14:104780214-104780214

UniProtKB/Swiss-Prot genetic disease variations for Proteus Syndrome:

73
# Symbol AA change Variation ID SNP ID
1 AKT1 p.Glu17Lys VAR_055422 rs121434592

Expression for Proteus Syndrome

Search GEO for disease gene expression data for Proteus Syndrome.

Pathways for Proteus Syndrome

Pathways related to Proteus Syndrome according to KEGG:

36
# Name Kegg Source Accession
1 PI3K-Akt signaling pathway hsa04151
2 mTOR signaling pathway hsa04150

Pathways related to Proteus Syndrome according to GeneCards Suite gene sharing:

(show top 50) (show all 180)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
14.35 TSC2 TSC1 RHEB PTEN PIK3R2 PIK3CA
2
Show member pathways
14.16 TSC2 PTEN PROS1 PIK3R2 PIK3CA NF1
3
Show member pathways
14.01 TSC2 TSC1 RHEB PTEN PIK3R2 NF1
4
Show member pathways
13.89 TSC2 PIK3R2 PIK3CA NF1 MTOR GPC3
5
Show member pathways
13.76 TSC2 TSC1 RHEB PIK3R2 PIK3CA MTOR
6
Show member pathways
13.67 PIK3R2 PIK3CA MTOR GNAS FGFR1 AKT3
7
Show member pathways
13.63 TSC2 PTEN PIK3R2 PIK3CA MTOR FGFR1
8
Show member pathways
13.61 TSC2 TSC1 PTEN PIK3R2 MTOR GNAS
9
Show member pathways
13.51 PROS1 PLEK PIK3R2 PIK3CA GNAS GNAQ
10
Show member pathways
13.39 PTEN PIK3R2 MTOR GNAS GNAQ AKT3
11
Show member pathways
13.33 TSC2 PTEN PIK3R2 PIK3CA MTOR FGFR1
12
Show member pathways
13.28 PIK3R2 PIK3CA GNAS GNAQ AKT3 AKT2
13
Show member pathways
13.27 PTEN PIK3R2 MTOR GNAS FGFR1 AKT3
14
Show member pathways
13.26 TSC2 TSC1 RHEB PIK3R2 MTOR GNAS
15
Show member pathways
13.18 TSC2 TSC1 RHEB PTEN MTOR AKT3
16
Show member pathways
13.17 TSC2 RHEB PTEN PIK3R2 PIK3CA MTOR
17
Show member pathways
13.15 TSC2 TSC1 RHEB PTEN PIK3R2 PIK3CA
18
Show member pathways
13.13 TSC2 TSC1 RHEB PIK3R2 PIK3CA MTOR
19
Show member pathways
13.12 TSC2 TSC1 RHEB PTEN PIK3R2 PIK3CA
20
Show member pathways
13.09 TNS1 PTEN PIK3R2 PIK3CA AKT3 AKT2
21
Show member pathways
13.09 PTEN PIK3R2 PIK3CA MTOR GNAS FGFR1
22
Show member pathways
13.08 TSC2 RHEB PTEN PIK3R2 PIK3CA MTOR
23 13.05 PTEN PIK3R2 PIK3CA MTOR GNAS GNAQ
24
Show member pathways
13.04 PIK3R2 PIK3CA GNAS AKT3 AKT2 AKT1
25
Show member pathways
13.03 PIK3R2 PIK3CA GNAQ AKT3 AKT2 AKT1
26 13.02 TSC2 TSC1 RHEB PIK3R2 PIK3CA MTOR
27
Show member pathways
13 PTEN PIK3R2 PIK3CA MTOR FGFR1 AKT3
28
Show member pathways
12.99 PTEN PIK3R2 PIK3CA MTOR AKT3 AKT2
29
Show member pathways
12.98 PIK3R2 PIK3CA GNAS GNAQ AKT3 AKT2
30
Show member pathways
12.97 PIK3R2 PIK3CA NF1 GNAS GNAQ FGFR1
31
Show member pathways
12.95 TSC2 PTEN PIK3R2 PIK3CA MTOR FGFR1
32
Show member pathways
12.93 PIK3R2 PIK3CA AKT3 AKT2 AKT1
33
Show member pathways
12.93 PIK3R2 PIK3CA AKT3 AKT2 AKT1
34
Show member pathways
12.93 PTEN PIK3R2 PIK3CA MTOR AKT3 AKT2
35
Show member pathways
12.9 PIK3R2 PIK3CA MTOR GNAS GNAQ AKT3
36 12.89 NF1 FGFR1 AKT3 AKT2 AKT1
37
Show member pathways
12.85 PTEN PIK3R2 PIK3CA NF1 MTOR AKT3
38
Show member pathways
12.84 TSC2 RHEB PIK3R2 PIK3CA MTOR GNAS
39
Show member pathways
12.82 PTEN PIK3R2 PIK3CA MTOR AKT3 AKT2
40
Show member pathways
12.81 PIK3R2 GNAS AKT3 AKT2 AKT1
41
Show member pathways
12.8 PIK3R2 PIK3CA AKT3 AKT2 AKT1
42
Show member pathways
12.79 PTEN PIK3R2 PIK3CA AKT3 AKT2 AKT1
43
Show member pathways
12.78 PIK3R2 PIK3CA AKT3 AKT2 AKT1
44
Show member pathways
12.78 PIK3R2 PIK3CA GNAS AKT3 AKT2 AKT1
45
Show member pathways
12.74 PIK3R2 PIK3CA AKT3 AKT2 AKT1
46
Show member pathways
12.74 PIK3R2 PIK3CA MTOR AKT3 AKT2 AKT1
47
Show member pathways
12.74 TSC2 TSC1 RHEB PTEN PIK3R2 PIK3CA
48
Show member pathways
12.72 PTEN PIK3R2 PIK3CA MTOR AKT3 AKT2
49
Show member pathways
12.71 PIK3R2 MTOR AKT3 AKT2 AKT1
50
Show member pathways
12.7 GNAS GNAQ AKT3 AKT2 AKT1

GO Terms for Proteus Syndrome

Cellular components related to Proteus Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 plasma membrane GO:0005886 10.13 TSC1 RHEB PTEN PROS1 PLEK PIK3CA
2 cytosol GO:0005829 10.07 TSC2 TSC1 RHEB PTEN PLEK PIK3R2
3 membrane GO:0016020 10.06 TSC2 TSC1 RHEB PROS1 PLEK PIK3CA
4 cytoplasm GO:0005737 9.53 TSC2 TSC1 TNS1 RHEB PTEN PLEK
5 TSC1-TSC2 complex GO:0033596 8.96 TSC2 TSC1

Biological processes related to Proteus Syndrome according to GeneCards Suite gene sharing:

(show all 36)
# Name GO ID Score Top Affiliating Genes
1 phosphorylation GO:0016310 10.05 PIK3CA MTOR FGFR1 AKT3 AKT2 AKT1
2 intracellular signal transduction GO:0035556 10.03 TNS1 PLEK AKT3 AKT2 AKT1
3 negative regulation of cell proliferation GO:0008285 10.02 TSC2 TSC1 PTEN NF1 GPC3
4 protein phosphorylation GO:0006468 10.02 PIK3CA MTOR FGFR1 AKT3 AKT2 AKT1
5 angiogenesis GO:0001525 9.95 PTEN PIK3CA FGFR1 AGGF1
6 cell projection organization GO:0030030 9.89 TSC1 PLEK MTOR AKT1
7 positive regulation of protein kinase B signaling GO:0051897 9.87 PIK3R2 PIK3CA MTOR FGFR1
8 peptidyl-serine phosphorylation GO:0018105 9.84 MTOR AKT3 AKT2 AKT1
9 insulin receptor signaling pathway GO:0008286 9.83 PIK3R2 AKT2 AKT1
10 phosphatidylinositol biosynthetic process GO:0006661 9.81 PTEN PIK3R2 PIK3CA
11 glucose metabolic process GO:0006006 9.79 PIK3CA AKT2 AKT1
12 negative regulation of protein kinase B signaling GO:0051898 9.78 TSC2 PTEN AKT1
13 phosphatidylinositol-mediated signaling GO:0048015 9.76 PIK3R2 PIK3CA FGFR1
14 positive regulation of blood vessel endothelial cell migration GO:0043536 9.73 FGFR1 AKT3 AKT1
15 cellular response to insulin stimulus GO:0032869 9.73 PTEN PIK3R2 AKT2 AKT1
16 negative regulation of protein kinase activity GO:0006469 9.71 TSC2 NF1 GNAQ AKT1
17 mammary gland epithelial cell differentiation GO:0060644 9.67 AKT2 AKT1
18 positive regulation of lipid biosynthetic process GO:0046889 9.67 MTOR AKT1
19 positive regulation of glucose import GO:0046326 9.67 GPC3 AKT2 AKT1
20 protein kinase B signaling GO:0043491 9.67 TSC2 PTEN PIK3CA AKT1
21 ruffle organization GO:0031529 9.66 PLEK MTOR
22 regulation of cell-matrix adhesion GO:0001952 9.66 TSC1 NF1
23 positive regulation of mitochondrial membrane potential GO:0010918 9.65 AKT2 AKT1
24 spinal cord development GO:0021510 9.65 NF1 MTOR AKT1
25 positive regulation of endothelial cell proliferation GO:0001938 9.65 NF1 MTOR AKT3 AKT1 AGGF1
26 positive regulation of glucose metabolic process GO:0010907 9.64 AKT2 AKT1
27 forebrain morphogenesis GO:0048853 9.63 PTEN NF1
28 positive regulation of TOR signaling GO:0032008 9.63 RHEB PIK3CA AKT3
29 regulation of glycogen biosynthetic process GO:0005979 9.62 MTOR AKT1
30 phosphatidylinositol 3-kinase signaling GO:0014065 9.62 PIK3R2 PIK3CA NF1 AKT1
31 peripheral nervous system myelin maintenance GO:0032287 9.6 AKT2 AKT1
32 cellular response to decreased oxygen levels GO:0036294 9.52 PTEN AKT1
33 negative regulation of plasma membrane long-chain fatty acid transport GO:0010748 9.51 AKT2 AKT1
34 negative regulation of macroautophagy GO:0016242 9.46 TSC1 PIK3CA MTOR AKT1
35 anoikis GO:0043276 9.26 TSC2 PIK3CA MTOR AKT1
36 negative regulation of cell size GO:0045792 8.92 TSC1 PTEN MTOR AKT1

Molecular functions related to Proteus Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.58 TSC2 TSC1 TNS1 RHEB PTEN PLEK
2 protein serine/threonine kinase activity GO:0004674 9.55 PIK3CA MTOR AKT3 AKT2 AKT1
3 kinase activity GO:0016301 9.43 PIK3CA MTOR FGFR1 AKT3 AKT2 AKT1

Sources for Proteus Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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