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European Journal of Case Reports in... 2021Proteus syndrome is an extremely rare disorder that manifests as an asymmetric, disproportionate overgrowth of any connective tissue, such as bone, fat or epidermal...
UNLABELLED
Proteus syndrome is an extremely rare disorder that manifests as an asymmetric, disproportionate overgrowth of any connective tissue, such as bone, fat or epidermal nevi, in a mosaic or patchy pattern. It has an estimated prevalence of less than 1/1,000,000 live births. The diagnosis can be difficult because the phenotypes of the patients are variable. Many individuals develop cutaneous capillary malformation and prominent varicosities (large and complex vascular malformations). Thus, Proteus syndrome patients are at risk of developing deep vein thrombosis and pulmonary embolism. The authors present the case of a patient with Proteus syndrome who was admitted because of pulmonary thromboembolism and presented hypertrophy of the left arm and left hemithorax.
LEARNING POINTS
Proteus syndrome is an extremely rare disorder that manifests as an asymmetric, disproportionate overgrowth of any connective tissue.The diagnosis can be difficult because the phenotypes are variable.It is important to keep in mind the importance of anticoagulation because patients are at risk of developing deep vein thrombosis and pulmonary embolism.
PubMed: 33987133
DOI: 10.12890/2021_002554 -
Cureus May 2024An uncommon congenital hamartomatous disorder called Proteus syndrome is characterized by multifocal tissue expansion originating from all three germinal layers....
An uncommon congenital hamartomatous disorder called Proteus syndrome is characterized by multifocal tissue expansion originating from all three germinal layers. Diagnosis mainly relies on clinical and radiological criteria. Here, we present a case of a 13-year-old female child exhibiting bony, soft tissue, and vascular abnormalities, along with developmental delay. We conclude by highlighting the importance of imaging studies in conjunction with physical examination, which are characterized by general and specific criteria to diagnose this rare condition until a specific gene test becomes available.
PubMed: 38860105
DOI: 10.7759/cureus.60072 -
American Journal of Medical Genetics.... Dec 2016The phosphatidylinositol-3-kinase (PI3K)/AKT/mTOR signaling pathway plays an essential role in regulation of normal cell growth, metabolism, and survival. Somatic... (Review)
Review
The phosphatidylinositol-3-kinase (PI3K)/AKT/mTOR signaling pathway plays an essential role in regulation of normal cell growth, metabolism, and survival. Somatic activating mutations in the PI3K/AKT/mTOR pathway are among the most common mutations identified in cancer, and have been shown to cause a spectrum of overgrowth syndromes including PIK3CA-Related Overgrowth Spectrum, Proteus syndrome, and brain overgrowth conditions. Clinical findings in these disorders may be isolated or multiple, including sporadic or mosaic overgrowth (adipose, skeletal, muscle, brain, vascular, or lymphatic), and skin abnormalities (including epidermal nevi, hyper-, and hypopigmented lesions), and have the potential risk of tumorigenesis. Key negative regulators of the PI3K-AKT signaling pathway include PTEN and TSC1/TSC2 and germline loss-of function mutations of these genes are established to cause PTEN Hamartoma Tumor Syndrome and Tuberous Sclerosis Complex. Mosaic forms of these conditions lead to increased activation of PI3K and mTOR at affected sites and there is phenotypic overlap between these conditions. All are associated with significant morbidity with limited options for treatment other than symptomatic therapies and surgeries. As dysregulation of the PI3K/AKT/mTOR pathway has been implicated in cancer, several small molecule inhibitors targeting different components of the PI3K/AKT/mTOR signaling pathway are under clinical investigation. The development of these therapies brings closer the prospect of targeting treatment for somatic PI3K/AKT/mTOR-related overgrowth syndromes. This review describes the clinical findings, gene function and pathogenesis of these mosaic overgrowth syndromes, and presents existing and future treatment strategies to reduce or prevent associated complications of these disorders. © 2016 Wiley Periodicals, Inc.
Topics: Growth Disorders; Humans; Mutation; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 27860216
DOI: 10.1002/ajmg.c.31531 -
The Journal of Investigative Dermatology Sep 2022Mosaicism results from postzygotic alterations during embryogenesis leading to genetically distinct populations of cells within individuals and has been historically...
Mosaicism results from postzygotic alterations during embryogenesis leading to genetically distinct populations of cells within individuals and has been historically recognized by phenotypes with visible, often patterned manifestations. Before the advent of molecular profiling assays and high-throughput sequencing, it was challenging to study mosaicism in human disease; however, the study of mosaic disorders has recently revealed unexpected and novel pathways for disease pathogenesis. In this paper, we will review the techniques for discovery of disease-causing alleles using Proteus syndrome; phakomatosis pigmentokeratotica; linear porokeratosis; and vacuoles, E1 enzyme, X-linked, autoinflammatory somatic syndrome as models. These tools represent powerful approaches for dissecting the genetic basis for human disorders.
Topics: Alleles; High-Throughput Nucleotide Sequencing; Humans; Mosaicism; Nevus, Pigmented; Proteus Syndrome; Skin Diseases, Genetic
PubMed: 35985765
DOI: 10.1016/j.jid.2022.07.001 -
Discovery Medicine Feb 2015Von Hippel-Lindau disease, Cowden syndrome, and Proteus syndrome are cancer syndromes which affect multiple organs and lead to significant decline in quality of life in... (Review)
Review
Von Hippel-Lindau disease, Cowden syndrome, and Proteus syndrome are cancer syndromes which affect multiple organs and lead to significant decline in quality of life in affected patients. These syndromes are rare and typically affect the adolescent and young adult population, resulting in greater cumulative years of life lost. Improved understanding of the underpinnings of the genetic pathways underlying these syndromes and the rapid evolution of targeted therapies in general have made it possible to develop therapeutic options for these patients and other genetic cancer syndromes. Targeted therapies especially antiangiogenics and inhibitors of the PIK3CA/AKT/mTOR signaling pathway have shown activity in selected group of patients affected by these syndromes or in patients harboring specific sporadic mutations which are otherwise characteristic of these syndromes. Unfortunately due to the rare nature, patients with these syndromes are not the focus of clinical trials and unique results seen in these patients can easily go unnoticed. Most of the data suggesting benefits of targeted therapies are either case reports or small case series. Thus, a literature review was indicated. In this review we explore the use of molecularly targeted therapy options in Von Hippel-Lindau disease, Cowden syndrome, and Proteus syndrome.
Topics: Hamartoma Syndrome, Multiple; Humans; Molecular Targeted Therapy; Neoplasms; Proteus Syndrome; Syndrome; von Hippel-Lindau Disease
PubMed: 25725225
DOI: No ID Found -
European Journal of Ophthalmology Sep 2023In this report we illustrate the ophthalmologic assessment of two patients affected by Proteus Syndrome (PS), an extremely rare genetic disorder. Case #1 describes a 26...
In this report we illustrate the ophthalmologic assessment of two patients affected by Proteus Syndrome (PS), an extremely rare genetic disorder. Case #1 describes a 26 year old male patient followed for multiple ophthalmic anomalies: a limbal dermoid cyst, a unilateral cataract, bilateral nystagmus, severe myopia and unilateral optic nerve head drusen. Case #2 describes a 20 year old female patient referred to our Ophthalmology Department for a routine ophthalmologic evaluation after being treated for 3 years with Miransertib (an experimental AKT-pathway inhibitor). Both patients underwent a complete ophthalmologic examination and a multimodal imaging evaluation. The multimodal imaging approach has revealed useful to evaluate both cases in detail and to keep track of disease evolution over time, moreover providing helpful features to further characterize this rare syndrome.
Topics: Male; Female; Humans; Young Adult; Adult; Proteus Syndrome; Eye Abnormalities; Nystagmus, Pathologic; Diagnostic Imaging; Myopia; Abnormalities, Multiple
PubMed: 36113118
DOI: 10.1177/11206721221125852 -
Experimental and Therapeutic Medicine Sep 2020Proteus syndrome (PS) is an extremely rare and sporadic disorder characterized by asymmetric and/or disproportionate overgrowth of limbs, hamartomas, and vascular...
Proteus syndrome (PS) is an extremely rare and sporadic disorder characterized by asymmetric and/or disproportionate overgrowth of limbs, hamartomas, and vascular malformations. The onset of overgrowth usually involves the skin, bone, fat, and other connective tissues in a patchy or mosaic pattern. Partial gigantism of the affected limb or digit is a pathognomonic sign of PS. Thus far, only a few cases of PS have been recorded in the literature. In the present report, a case of PS in a 35-year old woman with classic cerebriform plantar hyperplasia and macrodactyly of the left foot was documented. The clinical and molecular characteristics and differential diagnosis of PS are also discussed in this report.
PubMed: 32765766
DOI: 10.3892/etm.2020.8986 -
Turkish Journal of Anaesthesiology and... Dec 2022
PubMed: 36511499
DOI: 10.5152/TJAR.2021.21149 -
Romanian Journal of Morphology and... 2016A 46-year-old female patient presented with photosensitivity, symmetric arthritis, episodic plantar pain and strikingly redundant plantar skin folds, likely due to...
A 46-year-old female patient presented with photosensitivity, symmetric arthritis, episodic plantar pain and strikingly redundant plantar skin folds, likely due to lipoatrophy after recurrent episodes of plantar panniculitis. In this context, leukopenia with lymphopenia, thrombocytopenia and positive antinuclear antibodies were revelatory for systemic lupus erythematosus. However, a small cerebriform plantar collagenoma, along with discrete dysmorphic features with downslanting palpebral fissures and mild right ptosis, second and third syndactyly and a larger first right toe since childhood, and early-onset bilateral ovarian cystadenoma, suggested a minimal Proteus syndrome. Genetic confirmation could not be performed. As adipose tissue dysregulation may be a feature of Proteus syndrome, the possible mechanisms leading to localized lipoatrophy in this setting are discussed. This case enlights intriguing links between adipogenesis, inflammation and dysmorphology. From a practical point of view, finding and treating an over-imposed inflammation could help limit damage in a hamartomatous syndrome.
Topics: Female; Foot; Humans; Middle Aged; Proteus Syndrome; Skin Diseases
PubMed: 28002528
DOI: No ID Found -
Obstetric Medicine Dec 2021Proteus syndrome is a rare, multi-system, genetic syndrome characterised by atypical and excessive growth of skeletal tissue. Clinical presentations include abnormal...
Proteus syndrome is a rare, multi-system, genetic syndrome characterised by atypical and excessive growth of skeletal tissue. Clinical presentations include abnormal musculoskeletal growth and cutaneous lesions. Due to its rarity, there have been a limited number of published case reports of Proteus syndrome. This is the first case report on the management of Proteus syndrome in pregnancy. We present the case of a pregnant woman with Proteus syndrome in her first pregnancy in a large teaching hospital and discuss the considerations and challenges faced in her antenatal, intrapartum and postnatal care.
PubMed: 34880940
DOI: 10.1177/1753495X20970791