Proteus Syndrome

Hamartoneoplastic malformation syndrome of uncertain etiology characterized by partial GIGANTISM of the hands and/or feet, asymmetry of the limbs, plantar hyperplasia, hemangiomas (HEMANGIOMA), lipomas (LIPOMA), lymphangiomas (LYMPHANGIOMA), epidermal NEVI; MACROCEPHALY; cranial HYPEROSTOSIS, and long-bone overgrowth. Joseph Merrick, the so-called "elephant man", apparently suffered from Proteus syndrome and not NEUROFIBROMATOSIS, a disorder with similar characteristics.

Also Known As:

Networked: 59 relevant articles (3 outcomes, 5 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Lipoma (Lipomata)
2.	Hodgkin Disease (Hodgkin's Disease)
3.	Neoplasms (Cancer)
4.	Polymicrogyria
5.	Megalencephaly

Experts

1.	Biesecker, Leslie G: 9 articles (12/2021 - 08/2011)
2.	Sapp, Julie C: 5 articles (12/2021 - 08/2011)
3.	Schwartz, Brian: 5 articles (01/2020 - 01/2017)
4.	Keppler-Noreuil, Kim M: 5 articles (01/2019 - 08/2011)
5.	Lindhurst, Marjorie J: 5 articles (01/2019 - 08/2011)
6.	Darling, Thomas N: 4 articles (02/2021 - 08/2011)
7.	Resta, Nicoletta: 3 articles (01/2021 - 01/2018)
8.	Yu, Yi: 3 articles (01/2018 - 12/2015)
9.	Brockmann, Knut: 2 articles (01/2022 - 08/2011)
10.	Ranieri, Carlotta: 2 articles (01/2021 - 01/2019)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Proteus Syndrome:

1.	MiransertibIBA 01/01/2019 - "We conclude that 5 mg/m2/day of miransertib is an appropriate starting point for future efficacy trials and that this agent shows promise of therapeutic efficacy in children with Proteus syndrome." 01/01/2019 - "We designed a non-randomized, phase 0/1 pilot study of miransertib in adults and children with Proteus syndrome to identify an appropriate dosage starting point for a future efficacy trial using a pharmacodynamic endpoint. " 01/01/2019 - "Pharmacodynamic Study of Miransertib in Individuals with Proteus Syndrome." 12/01/2021 - "We present the 5-yr follow-up of an 18-yr-old male with Proteus syndrome treated with miransertib (MK-7075), an oral pan-AKT inhibitor. " 12/01/2021 - "Case report: five-year experience of AKT inhibition with miransertib (MK-7075) in an individual with Proteus syndrome."
2.	Brentuximab VedotinIBA 07/01/2015 - "Brentuximab vedotin in the treatment of a patient with refractory Hodgkin disease and Proteus syndrome - a case report and discussion." 07/01/2015 - "We report a patient with Proteus syndrome and relapsed Hodgkin lymphoma, whose remission was finally achieved after brentuximab vedotin therapy, allowing her to receive a haploidentical stem cell transplant. "
3.	Phosphatidylinositol 3-Kinase (1 Phosphatidylinositol 3 Kinase)IBA 03/01/2017 - "Genetic mosaicism, such as mutations involving the phosphoinositide 3 kinase-AKT pathway in the affected tissues, may be important causes of Proteus syndrome. " 01/01/2017 - "Recent studies have discovered a group of overgrowth syndromes, such as congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies (CLOVES) syndrome, Proteus syndrome, and megalencephaly-capillary malformation-polymicrogyria (MCAP) syndrome, are caused by somatic activating variants in genes involved in the phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin pathway. "
4.	Sirolimus (Rapamycin)FDA Link 12/01/2021 - "Reduction of Disease Burden With Early Sirolimus Treatment in a Child With Proteus Syndrome." 01/01/2017 - "Recent studies have discovered a group of overgrowth syndromes, such as congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies (CLOVES) syndrome, Proteus syndrome, and megalencephaly-capillary malformation-polymicrogyria (MCAP) syndrome, are caused by somatic activating variants in genes involved in the phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin pathway. "
5.	DNA (Deoxyribonucleic Acid)IBA 10/01/2004 - "In this study, affected and unaffected tissue from six patients diagnosed with Proteus syndrome were screened by direct sequencing of genomic DNA to determine if there might be an association between germ-line or somatic mutations in PTEN or GPC3 and the development of Proteus syndrome. " 08/18/2011 - "We performed exome sequencing of DNA from biopsy samples obtained from patients with the Proteus syndrome and compared the resultant DNA sequences with those of unaffected tissues obtained from the same patients. " 08/18/2011 - "We confirmed and extended an observed association, using a custom restriction-enzyme assay to analyze the DNA in 158 samples from 29 patients with the Proteus syndrome. "
6.	TensinsIBA 04/01/2022 - "Proteus-Like Syndrome: A Rare Phenotype of Phosphatase and Tensin Homolog Hamartoma Tumor Syndrome." 02/01/2016 - "Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) may manifest as one of four distinctive disorders: 1) Cowden syndrome; 2) Bannayan-Riley-Ruvalcaba syndrome; 3) Proteus syndrome; or 4) Proteus-like syndrome. " 01/10/2013 - "PTEN gene (phosphatase and tensin homolog deleted on chromosome ten, MIM 601628) is a tumor suppressor gene implicated in PTEN hamartoma tumor syndromes (PHTS) including Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome and Proteus-like syndrome. " 09/18/2008 - "Germline PTEN (Phosphatase and TENsin homologue deleted on chromosome TEN) mutations predispose to phenotypically diverse disorders that share several overlapping clinical features: Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome and Proteus-like syndrome, collectively classified as PTEN hamartoma tumour syndrome (PHTS). " 03/01/2019 - "The clinical presentations, diagnostic and imaging workups, and treatment options available for patients with Klippel-Trenaunay syndrome, CLOVES (congenital lipomatous overgrowth, vascular anomalies, epidermal nevi, and scoliosis/spinal deformities) syndrome, fibroadipose vascular anomaly, phosphatase and tensin homolog mutation spectrum, Parkes-Weber syndrome, and Proteus syndrome are reviewed. "
7.	Phosphoric Monoester Hydrolases (Phosphatases)IBA 04/01/2022 - "Proteus-Like Syndrome: A Rare Phenotype of Phosphatase and Tensin Homolog Hamartoma Tumor Syndrome." 02/01/2016 - "Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) may manifest as one of four distinctive disorders: 1) Cowden syndrome; 2) Bannayan-Riley-Ruvalcaba syndrome; 3) Proteus syndrome; or 4) Proteus-like syndrome. " 01/10/2013 - "PTEN gene (phosphatase and tensin homolog deleted on chromosome ten, MIM 601628) is a tumor suppressor gene implicated in PTEN hamartoma tumor syndromes (PHTS) including Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome and Proteus-like syndrome. " 03/01/2019 - "The clinical presentations, diagnostic and imaging workups, and treatment options available for patients with Klippel-Trenaunay syndrome, CLOVES (congenital lipomatous overgrowth, vascular anomalies, epidermal nevi, and scoliosis/spinal deformities) syndrome, fibroadipose vascular anomaly, phosphatase and tensin homolog mutation spectrum, Parkes-Weber syndrome, and Proteus syndrome are reviewed. " 08/01/2017 - "In this article, which is part 2 of a two-part series, the authors review the most relevant clinical and sonographic features of arteriovenous, capillary, venous and lymphatic malformations as well as vascular malformations that are part of more complex conditions or associated with syndromes, including Parkes-Weber syndrome, phosphatase and tensin homologue (PTEN) hamartoma tumor syndromes, Klippel-Trénaunay syndrome, CLOVES (congenital lipomatous overgrowth, vascular malformations, epidermal nevi and skeletal anomalies) syndrome, fibro-adipose vascular anomaly and Proteus syndrome."
8.	Therapeutic UsesIBA 01/01/2021 - "Following recent results of the use of AKT inhibitors in Proteus syndrome (PS) and AKT-mutant cancers, we investigated its therapeutic use in two patients with severe PROS who had exhausted conventional treatment methods. " 01/01/2019 - "First evidence of a therapeutic effect of miransertib in a teenager with Proteus syndrome and ovarian carcinoma."
9.	Intercellular Signaling Peptides and Proteins (Growth Factors)IBA 12/01/2003 - "This is the 1st report showing that the Proteus syndrome may be associated with a chromosome 16 anomaly; while previous findings suggested that this syndrome was associated with a modification of chromosome 1. As the pathologic hypothesis of this syndrome possibly involves lethal genes in somatic mosaicism, responsible for control of cellular proliferation and/or alteration in the mechanism of action of some growth factors, chromosomal alterations found in the patient described in this work may suggest the location of the genes involved in this syndrome." 04/01/1994 - "The Proteus syndrome is a muscular dysgenesis; abnormal paracrine growth factors and perhaps altered genes that regulate muscle differentiation and growth, such as myoD and myogenin, are the suspected cause. "
10.	Retinaldehyde (Retinal)IBA 01/01/2021 - "Misaligned foveal morphology and sector retinal dysfunction in AKT1-mosaic Proteus syndrome." 07/31/2000 - "Multiple meningiomas, craniofacial hyperostosis and retinal abnormalities in Proteus syndrome."

Therapies and Procedures

1.	Therapeutics 12/01/2021 - "Inhibitors of AKT, originally designed as cancer therapeutics, are a rational, targeted pharmacologic strategy to mitigate the devastating morbidity of Proteus syndrome. " 02/01/2015 - "In this review we explore the use of molecularly targeted therapy options in Von Hippel-Lindau disease, Cowden syndrome, and Proteus syndrome. " 02/01/2015 - "Targeted therapy for genetic cancer syndromes: Von Hippel-Lindau disease, Cowden syndrome, and Proteus syndrome." 07/01/2015 - "We report a patient with Proteus syndrome and relapsed Hodgkin lymphoma, whose remission was finally achieved after brentuximab vedotin therapy, allowing her to receive a haploidentical stem cell transplant. "
2.	Operative Surgical Procedures 01/01/2022 - "We conclude that oligosymptomatic Proteus syndrome should be considered in progressive intraosseous lipoma, as recognition of this diagnosis has relevant implications for genetic counseling and opens novel treatment options with AKT1 inhibitors rather than surgical procedures."
3.	Orthopedic Procedures 07/01/2019 - "A mosaic somatic mutation of AKT1 gene is one of the pathogenic mutations for Proteus syndrome, and orthopedic surgery may be a good way to improve symptoms of the disease. " 10/01/2014 - "We had the opportunity of treating many children who were afflicted by overgrowth syndromes and have been previously misdiagnosed as Proteus Syndrome in our department of pediatric and orthopedic surgery of "Maria Sklodowska Curie" Clinical Emergency Hospital for Children. "
4.	Transplantation 01/01/1995 - "The indications for transplantation have been diverse, primary pulmonary hypertension (10), cystic fibrosis (11), congenital heart disease (10), arteriovenous malformation (3), emphysema (1), graft-versus-host disease (1), rheumatoid lung (1), cardiomyopathy (1), desquamative interstitial pneumonitis (1), and Proteus syndrome (1). " 02/01/1994 - "Indications for transplantation included cystic fibrosis (n = 9), congenital heart disease with Eisenmenger complex (n = 9), primary pulmonary hypertension (n = 8), pulmonary arteriovenous malformations (n = 2), desquamative interstitial pneumonia (n = 2), Proteus syndrome with multicystic pulmonary disease (n = 1), graft-versus-host disease (n = 1), rheumatoid lung disease (n = 1), and bronchiolitis obliterans and emphysema (n = 1). "
5.	Anesthesia 01/01/2019 - "Selection of anesthesia for lower extremity surgery of patients with Proteus Syndrome." 08/01/2004 - "There are few previous reports on anesthesia in a patient with Proteus syndrome." 08/01/2004 - "Anesthesia for proteus syndrome."