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Radiologia 2019Vascular malformations and tumors, also known as "vascular anomalies", comprise an extensive variety of lesions involving all parts of the body. Due to a lack of a... (Review)
Review
Vascular malformations and tumors, also known as "vascular anomalies", comprise an extensive variety of lesions involving all parts of the body. Due to a lack of a complete understanding of the origin and histopathology of such lesions, this field has been traditionally obscured by the use of an unclear nomenclature. Knowledge of the classification and clinical and imaging characteristics of this group of lesions is paramount when managing these patients. The objective of this series of two articles is to review the current classification of vascular anomalies, to describe the role of imaging in their diagnosis, to summarize their distinctive histopathologic, clinical and imaging features, and to discuss the treatment options. High-flow lesions were discussed in the first article of this series. In this second article, we will focus on low-flow lesions, including complex syndromes with associated low-flow malformations.
Topics: Adipose Tissue; Humans; Klippel-Trenaunay-Weber Syndrome; Lymphatic System; Nevus, Blue; Port-Wine Stain; Proteus Syndrome; Regional Blood Flow; Skin Neoplasms; Soft Tissue Neoplasms; Sturge-Weber Syndrome; Vascular Malformations; Veins
PubMed: 30292466
DOI: 10.1016/j.rx.2018.02.012 -
Journal of the American Academy of... Feb 2021Proteus syndrome is an overgrowth disorder caused by a mosaic activating AKT1 variant. Hair abnormalities in Proteus syndrome have rarely been reported, and frequencies... (Observational Study)
Observational Study
BACKGROUND
Proteus syndrome is an overgrowth disorder caused by a mosaic activating AKT1 variant. Hair abnormalities in Proteus syndrome have rarely been reported, and frequencies of such findings have not been elucidated.
OBJECTIVE
To define the types and frequencies of hair findings in individuals with Proteus syndrome.
METHODS
A cross-sectional study was conducted of individuals with clinical features of Proteus syndrome and a confirmed pathogenic variant in AKT1 evaluated between November 1996 and June 2019 at the National Institutes of Health Clinical Center. Medical records were reviewed for patterning, density, and color of hair on the body and scalp.
RESULTS
Of 45 individuals evaluated, 29 (64%) had asymmetric hypertrichosis on the body. This included unilateral blaschkoid hypertrichotic patches overlying normal skin or epidermal nevi in 16 (36%), unilateral nonblaschkoid hypertrichotic patches in 11 (24%), and unilateral limb hypertrichosis in 10 (22%). Diffuse, scattered, or patchy changes in scalp hair density or color were present in 11 individuals (24%).
LIMITATIONS
The retrospective, observational design, and limited longitudinal follow-up.
CONCLUSIONS
Asymmetric variations in hair distribution, thickness, length, and color contribute to the overall mosaic appearance of the skin in Proteus syndrome, an observation that provides novel insights into the role of phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling in skin appendage development.
Topics: Adolescent; Adult; Child; Child, Preschool; Cross-Sectional Studies; DNA Mutational Analysis; Female; Hair Follicle; Humans; Hypertrichosis; Male; Mosaicism; Mutation; Phosphatidylinositol 3-Kinases; Prevalence; Proteus Syndrome; Proto-Oncogene Proteins c-akt; Retrospective Studies; Signal Transduction; Young Adult
PubMed: 32035943
DOI: 10.1016/j.jaad.2020.01.078 -
Diagnostics (Basel, Switzerland) Jan 2022Since the development of modern cultivation and sequencing techniques, the human microbiome has increasingly become the focus of scientific attention. Even in the... (Review)
Review
Since the development of modern cultivation and sequencing techniques, the human microbiome has increasingly become the focus of scientific attention. Even in the bladder, long considered to be a sterile niche, a highly variable and complex microbial colonization has now been demonstrated. Especially in the context of diseases such as interstitial cystitis, whose etiopathogenesis is largely unknown, and whose diagnosis is based on a process of exclusion of confusable diseases, science hopes to gain far-reaching insights for etiology and diagnosis, including the identification of potential biomarkers. While for functional disorders such as urge urinary incontinence and overactive bladder syndrome, initial associations have been demonstrated between reduced microbial diversity and increased symptomatology, as well as shifts in the abundance of specific microorganisms such as or , studies in interstitial cystitis show conflicting results and have failed to identify a putative organism or urotype that clearly distinguishes the urinary microbiome of patients with IC/BPS from that of healthy controls. At the present time, therefore, the new insights into the bladder microbiome and its potential influence on urologic disease cannot yet be used in the context of elucidating possible etiopathogenetic causes, as well as in the use of a biomarker for diagnostic or prognostic purposes. Further studies should focus primarily on uniform procedures and detection methods to achieve better comparability of results and increase the likelihood of detecting hidden patterns.
PubMed: 35204374
DOI: 10.3390/diagnostics12020281 -
Clinical Medicine (London, England) May 2023
Topics: Humans; Urinary Tract Infections; Anti-Bacterial Agents; Syndrome
PubMed: 37236799
DOI: 10.7861/clinmed.2023-0132 -
Pediatric Dermatology Jul 2021Proteus syndrome, caused by a mosaic activating AKT1 variant, typically presents in toddlers with progressive, asymmetric overgrowth of the skin and bones. We aimed to...
BACKGROUND/OBJECTIVE
Proteus syndrome, caused by a mosaic activating AKT1 variant, typically presents in toddlers with progressive, asymmetric overgrowth of the skin and bones. We aimed to define the spectrum of dermatologic disease in individuals with genetically confirmed Proteus syndrome.
METHODS
We conducted a retrospective review of records from dermatologic examinations of individuals evaluated at the NIH with a molecular diagnosis of Proteus syndrome. The types, prevalence, and localization of dermatologic findings were assessed.
RESULTS
Fifty-one individuals (29 males, 22 females, mean age: 9 years) with clinical features of Proteus syndrome had the mosaic c.49G>A, p.Glu17Lys AKT1 variant. Fifty (98%) had at least one cutaneous feature constituting current clinical diagnostic criteria, including vascular malformations in 42 (82%), epidermal nevus in 41 (80%), volar cerebriform connective tissue nevi in 34 (67%), and adipose dysregulation in 30 (59%). Forty-nine (96%) had at least one dermatologic finding not included within the diagnostic criteria, including confluent volar skin-colored to hypopigmented papules or nodules (n = 33, 65%), papules or nodules on the digits or face (n = 27, 53%), and nonlinear epidermal nevi (n = 15, 29%). Other frequently observed features include nail changes (n = 28, 55%), hyperpigmented macules (n = 27, 53%), patchy dermal hypoplasia (n = 18, 35%), gingival/oral mucosal overgrowth (n = 17, 33%), hypopigmented macules (n = 16, 31%), dental enamel changes (n = 9, 18%), acrochordons (n = 6, 12%), and lingual overgrowth (n = 4, 8%).
CONCLUSIONS
The range of mucocutaneous features occurring in Proteus syndrome is broader than previously considered. These observations may assist in earlier diagnosis and management and provide novel insights regarding the pathogenesis of the condition.
Topics: Child; Female; Humans; Male; Nevus; Proteus Syndrome; Retrospective Studies; Skin Neoplasms; Vascular Malformations
PubMed: 34105192
DOI: 10.1111/pde.14624 -
Medicina (Kaunas, Lithuania) May 2024PTEN Hamartoma Tumour Syndrome (PHTS) encompasses diverse clinical phenotypes, including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), Proteus syndrome... (Review)
Review
PTEN Hamartoma Tumour Syndrome (PHTS) encompasses diverse clinical phenotypes, including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), Proteus syndrome (PS), and Proteus-like syndrome. This autosomal dominant genetic predisposition with high penetrance arises from heterozygous germline variants in the PTEN tumour suppressor gene, leading to dysregulation of the PI3K/AKT/mTOR signalling pathway, which promotes the overgrowth of multiple and heterogenous tissue types. Clinical presentations of CS range from benign and malignant disorders, affecting nearly every system within the human body. CS is the most diagnosed syndrome among the PHTS group, notwithstanding its weak incidence (1:200,000), for which it is considered rare, and its precise incidence remains unknown among other important factors. The literature is notably inconsistent in reporting the frequencies and occurrences of these disorders, adding an element of bias and uncertainty when looking back at the available research. In this review, we aimed to highlight the significant disparities found in various studies concerning CS and to review the clinical manifestations encountered in CS patients. Furthermore, we intended to emphasize the great significance of early diagnosis as patients will benefit from a longer lifespan while being unceasingly advised and supported by a multidisciplinary team.
Topics: Female; Humans; Hamartoma Syndrome, Multiple; Proteus Syndrome; PTEN Phosphohydrolase; Male
PubMed: 38792950
DOI: 10.3390/medicina60050767 -
Current Cancer Drug Targets Mar 2013AKT/PKB (Protein Kinase B) are central proteins mediating signals from receptor tyrosine kinases and phosphatidylinositol 3-kinase. AKT kinases are involved in a number... (Review)
Review
AKT/PKB (Protein Kinase B) are central proteins mediating signals from receptor tyrosine kinases and phosphatidylinositol 3-kinase. AKT kinases are involved in a number of important cellular processes including cell proliferation and survival, cell size in response to nutrient availability, tumor invasion/metastasis, and angiogenesis.Various components of the AKT signaling pathway are encoded by tumor suppressor genes and oncogenes whose loss or activation, respectively, plays an important role in tumorigenesis. The growing body of evidence connecting deregulated AKT signaling with sporadic human cancers and inherited cancer predisposition syndromes is discussed. We also highlight new findings regarding the involvement of activating mutations of AKT1, AKT2, and AKT3 in somatic overgrowth disorders: Proteus syndrome, hypoglycemia with hypertrophy, and hemimegalencephaly, respectively. In addition, we review recent literature documenting the various ways the AKT signaling pathway is activated in human cancers and consequences for molecularly targeted therapies.
Topics: Animals; Cell Transformation, Neoplastic; Disease Models, Animal; Enzyme Activation; Humans; Mice; Models, Biological; Neoplasm Proteins; Neoplasms; Proto-Oncogene Proteins c-akt; Signal Transduction
PubMed: 23297823
DOI: 10.2174/1568009611313030002 -
Iranian Journal of Pediatrics Jun 2012Proteus syndrome is a very rare condition with less than 100 confirmed cases reported worldwide. We report a case of Proteus syndrome in a two-year-old male who has...
BACKGROUND
Proteus syndrome is a very rare condition with less than 100 confirmed cases reported worldwide. We report a case of Proteus syndrome in a two-year-old male who has hemophilia A comorbidity.
CASE PRESENTATION
A two-year-old male patient was admitted with the chief complaint of severe bleeding in mouth cavity after trauma for two weeks. At admission he was found to have petechiae on buccal mucosa and fecal discoloration due to GI bleeding. We noted multiple abnormalities in his musculoskeletal system and skin. He had lymph edema in left leg, hemihypertrophy, macrodactyly in both foots and macrocephaly. With the history of severe bleeding and recurrent blood product transfusion, we suspected a hemorrhagic disorder. The reduced level of Factor VIII activity confirmed the diagnosis of hemophilia A. Considering patient's various musculoskeletal abnormalities according to the diagnostic criteria and after ruling out similar disorders the diagnosis of Proteus syndrome was established.
CONCLUSION
Because of the variability of clinical features, Proteus syndrome can be confused with other disorders of multiple tissue overgrowth. Our case of Proteus syndrome, who had hemophilia A comorbidity outlines the challenges in diagnosis of such rare combination of diseases.
PubMed: 23056896
DOI: No ID Found -
Disease Models & Mechanisms Feb 2023Somatic mutations occur frequently and can arise during embryogenesis, resulting in the formation of a patchwork of mutant clones. Such mosaicism has been implicated in...
Somatic mutations occur frequently and can arise during embryogenesis, resulting in the formation of a patchwork of mutant clones. Such mosaicism has been implicated in a broad range of developmental anomalies; however, their etiology is poorly understood. Patients carrying a common somatic oncogenic mutation in either PIK3CA or AKT1 can present with disproportionally large digits or limbs. How mutant clones, carrying an oncogenic mutation that often drives unchecked proliferation, can lead to controlled and coordinated overgrowth is unknown. We use zebrafish to explore the growth dynamics of oncogenic clones during development. Here, in a subset of clones, we observed a local increase in proportion of the fin skeleton closely resembling overgrowth phenotypes in patients. We unravel the cellular and developmental mechanisms of these overgrowths, and pinpoint the cell type and timing of clonal expansion. Coordinated overgrowth is associated with rapid clone expansion during early pre-chondrogenic phase of bone development, inducing a heterochronic shift that drives the change in bone size. Our study details how development integrates and translates growth potential of oncogenic clones, thereby shaping the phenotypic consequences of somatic mutations.
Topics: Animals; Mutation; Zebrafish; Phenotype; Mosaicism; Clone Cells
PubMed: 36621776
DOI: 10.1242/dmm.049793 -
The Journal of Molecular Diagnostics :... Jul 2017Somatic variants have been well described in tumorigenesis; however, they are only recently appreciated in other human disorders, such as mosaic overgrowth syndromes.... (Review)
Review
Somatic variants have been well described in tumorigenesis; however, they are only recently appreciated in other human disorders, such as mosaic overgrowth syndromes. Although overgrowth is a manifestation in many genetic syndromes, not all overgrowth syndromes are inherited. Mosaic somatic variants have been lately described in several overgrowth disorders, such as Proteus syndrome, CLOVES (congenital, lipomatous, overgrowth, vascular malformations, epidermal nevi, and spinal/skeletal anomalies and/or scoliosis) syndrome, and megalencephalyepolymicrogyria-polydactyly-hydrocephalus syndrome. These syndromes are caused by somatic variants in the genes associated with the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway, resulting in a spectrum of overgrowth syndromes with overlapping features that could be difficult to distinguish based on phenotypic presentations alone. In addition, Sanger sequencing is ineffective for the detection of a causal variant because of the mosaic nature of these variants, whereas targeted next-generation sequencing technology offers a deeper sequencing coverage and allows the detection of low-level mosaicism. Recent studies have shown that the causal variants are only present in the affected tissues in most cases, and can be enriched by in vitro tissue culture. In this review, we describe several mosaic somatic overgrowth syndromes caused by variants in genes of the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathway, their phenotypic and molecular spectrum, and the clinical utility of next-generation sequencing technology in the diagnosis of these disorders.
Topics: Animals; Clinical Trials as Topic; Female; Fingers; Genetic Testing; Genetic Variation; High-Throughput Nucleotide Sequencing; Humans; Hydrocephalus; Hypoglycemia; Limb Deformities, Congenital; Lipoma; Malformations of Cortical Development; Mosaicism; Musculoskeletal Abnormalities; Nevus; Phosphatidylinositol 3-Kinase; Polydactyly; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases; Vascular Malformations
PubMed: 28502730
DOI: 10.1016/j.jmoldx.2017.04.001