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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 -
In Vivo (Athens, Greece) 2021Proteus syndrome is a sporadic disease that is particularly noticeable due to the disproportional growth of body segments. The disease is a genetic mosaic. The mutations...
BACKGROUND/AIM
Proteus syndrome is a sporadic disease that is particularly noticeable due to the disproportional growth of body segments. The disease is a genetic mosaic. The mutations can arise from any of the germ layers, an explanation of the very variable phenotype. The aim of this report is to communicate the diagnosis and management of an unusual case of Proteus Syndrome with special attention to oral and craniofacial findings.
CASE REPORT
A 15-year-old patient was referred for surgical treatment of pronounced skull malformations and correction of oral mucosal hyperplasia. Treatment caused significant improvement in facial appearance and oral soft tissue conditions.
CONCLUSION
Surgical measures adapted to the local findings and symptoms can often relieve severe disfigurement of the patient.
Topics: Adolescent; Humans; Hyperplasia; Mutation; Phenotype; Proteus Syndrome
PubMed: 33910840
DOI: 10.21873/invivo.12415 -
Frontiers in Pediatrics 2020[This corrects the article DOI: 10.3389/fped.2020.574857.].
[This corrects the article DOI: 10.3389/fped.2020.574857.].
PubMed: 33425822
DOI: 10.3389/fped.2020.624141 -
American Journal of Medical Genetics.... Jan 2015Proteus syndrome (PS) is a rare, mosaic disorder with asymmetric and distorting overgrowth of the skeletal system, skin, and adipose tissues. Cardiac abnormalities are...
Proteus syndrome (PS) is a rare, mosaic disorder with asymmetric and distorting overgrowth of the skeletal system, skin, and adipose tissues. Cardiac abnormalities are rare in this syndrome and only two prior cases have been reported. Many patients with PS followed at our institution underwent transthoracic echocardiograms for preoperative evaluation or as work-up for associated pulmonary disease. Some were noted to have prominent, focal echodense areas in the myocardium. We further investigated cardiac findings in a cohort of children and adult patients with PS. Patients with abnormal echocardiograms were referred for cardiac magnetic resonance imaging, Holter monitoring, and exercise treadmill testing. Twenty children and adults with PS, age 24 months to 50 years old, underwent transthoracic echocardiograms. Seven patients (35%) had focal bright echodense areas within the myocardium suggesting fatty infiltration. The majority of patients had significant involvement of the interventricular septum. The cardiac characteristics of all patients with fatty infiltration on transthoracic echocardiograms were compared to Proteus patients without these findings. There were no significant differences in chamber sizes, mass, systolic or diastolic function. No increased risk of conduction defects or arrhythmias was found. This study shows that abnormal fat overgrowth is a common finding in the myocardium in patients with Proteus syndrome; however, it is not associated with functional derangements or arrhythmias. Further evaluation of a larger number of Proteus patients is needed in order to determine the frequency and prognosis of cardiac involvement. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
Topics: Adipose Tissue; Adolescent; Adult; Child; Child, Preschool; Female; Humans; Male; Myocardium; Proteus Syndrome; Ultrasonography; Young Adult
PubMed: 25377688
DOI: 10.1002/ajmg.a.36773 -
American Journal of Medical Genetics.... Sep 2022Proteus syndrome (PS) is a rare segmental overgrowth disorder caused by a mosaic activating variant in AKT1. The features of PS are often not present at birth but...
Proteus syndrome (PS) is a rare segmental overgrowth disorder caused by a mosaic activating variant in AKT1. The features of PS are often not present at birth but develop during the first few years of life. We describe a 55-year-old female, whose first symptom of overgrowth, a cerebriform connective tissue nevus, occurred at 19 years of age. We report the identification of the AKT1 c.49G > A p.(Glu17Lys) variant in this progressive lesion, the bony overgrowth, and recurrence after surgical intervention. In the sixth decade of life, this individual developed intraductal papillomas within her right breast which were confirmed to contain the same activating AKT1 variant as the connective tissue nevus. While similar neoplasms have been described in an individual with Proteus syndrome, none has been evaluated for the presence of the AKT1 variant. The tumor also contained two likely pathogenic variants in PIK3R1, c.1392_1403dupTAGATTATATGA p.(Asp464_Tyr467dup) and c.1728_1730delGAG p.(Arg577del). The finding of additional genetic variation putatively affecting the PI3K/AKT pathway in the neoplastic tissue may provide preliminary evidence of a molecular mechanism for tumorigenesis in PS. The late onset of symptoms and molecular characterization of the breast tumor expand the clinical spectrum of this rare disorder.
Topics: Breast Neoplasms; Female; Humans; Infant, Newborn; Middle Aged; Nevus; Papilloma, Intraductal; Phosphatidylinositol 3-Kinases; Proteus Syndrome; Proto-Oncogene Proteins c-akt
PubMed: 35441778
DOI: 10.1002/ajmg.a.62761 -
Annals of the American Thoracic Society Nov 2022Limited information is available regarding cystic lung disease in syndrome, a rare overgrowth disorder caused by a somatic activating variant in . To define the...
Limited information is available regarding cystic lung disease in syndrome, a rare overgrowth disorder caused by a somatic activating variant in . To define the phenotype of cystic lung disease in syndrome. Medical records, pulmonary function tests, and chest computed tomography of 39 individuals with syndrome evaluated at a single center were retrospectively reviewed. Lung histopathology from five affected individuals was examined. Cystic lung disease affected 26 (67%) of 39 individuals. The mean age of affected individuals was 17.1 years. The lung cysts varied in size and location. Focal regions of heterogeneous lung parenchyma resembling emphysema were found in 81% of affected individuals. Mass effect was seen in 12% of affected individuals; pneumothorax occurred in one. Dyspnea and respiratory infections were reported by 38% and 35% of affected individuals, respectively. Abnormal pulmonary function and scoliosis were found in 96% of affected individuals. Lung disease progressed in seven of 10 affected individuals, and all five affected individuals younger than 20 years of age had progressive cystic lung disease. Three affected individuals had symptomatic improvement after lung resection. Histopathology showed cystic air space enlargement of varying severity. Cystic lung disease is common in syndrome and is likely to progress in affected individuals younger than 20 years of age. Screening asymptomatic individuals with syndrome for cystic lung disease is indicated. Surgical lung resection is a therapeutic option for affected individuals with severe disease. Clinical trial registered with www.clinicaltrials.gov (NCT00001403).
Topics: Humans; Proteus Syndrome; Retrospective Studies; Lung Diseases; Phenotype; Pulmonary Emphysema; Cysts
PubMed: 35839129
DOI: 10.1513/AnnalsATS.202111-1214OC -
American Journal of Medical Genetics.... Dec 2018Proteus syndrome (PS) is a rare disorder caused by a mosaic AKT1 variant that comprises patchy overgrowth of tissues derived from all three germinal layers affecting...
Proteus syndrome (PS) is a rare disorder caused by a mosaic AKT1 variant that comprises patchy overgrowth of tissues derived from all three germinal layers affecting multiple viscera. We sought to delineate the extent of hepatoportal manifestations in patients with PS. We identified patients with PS who had abdominal imaging from 1989 to 2015 in a natural history study. Imaging was characterized for evidence of focal findings in the liver, spleen, and portal vasculature and for organomegaly. Relevant clinical and laboratory data were compared among those with or without organomegaly. Abdominal imaging was available on 38 patients including 20 who had serial studies. Nine patients had focal hepatic lesions including vascular malformations (VMs). Focal splenic abnormalities were noted in seven patients. Patients without cutaneous VMs did not have visceral VMs. Nine patients had splenomegaly, 12 had portal vein dilation, and 4 had hepatomegaly. There was a weak correlation of portal vein dilation to spleen height ratio (r = 0.18, p < .05). On laboratory evaluation, hepatic function was normal but there was thrombocytopenia in those with splenomegaly; platelet counts were 179 ± 87K/μL compared to those with normal spleen size at 253 ± 57K/μL (p < .05). Overall, focal hepatosplenic abnormalities occurred in 11 of 38 (29%) patients with PS. Splenomegaly and portal venous dilation were both found in 8 of 38 (21%) patients; however, other than relative thrombocytopenia, there was no evidence of portal hypertension. Although the AKT1-E17K somatic variant is a suspected oncogene, there were no malignant lesions identified in this study.
Topics: Adolescent; Adult; Biomarkers; Biopsy; Child; Female; Humans; Male; Multimodal Imaging; Phenotype; Portal Vein; Proteus Syndrome; Spleen; Young Adult
PubMed: 30346092
DOI: 10.1002/ajmg.a.40636 -
American Journal of Medical Genetics.... Nov 2013Numerous parallelisms exist between development and cancer. In this article, I review some of the founding ideas linking development and cancer, and highlight clinical... (Review)
Review
Numerous parallelisms exist between development and cancer. In this article, I review some of the founding ideas linking development and cancer, and highlight clinical conditions exhibiting features of both developmental derangement and cancer predisposition, including cohesinopathies, rasopathies, phakomatoses, Proteus syndrome and other overgrowth disorders, recessive chromosome breakage syndromes, and dominant hereditary cancer syndromes. I suggest that these disorders encompass a continuous spectrum spanning clinical genetics and clinical oncology, and derive some general implications that might be useful in the future for the treatment of these diseases.
Topics: Developmental Disabilities; Epigenesis, Genetic; Genetic Predisposition to Disease; Humans; Neoplasms; Phenotype
PubMed: 24123833
DOI: 10.1002/ajmg.a.36267 -
Frontiers in Pediatrics 2020Lateralized overgrowth (LO), or segmental overgrowth, is defined as an increase in growth of tissue (bone, muscle, connective tissue, vasculature, etc.) in any region of... (Review)
Review
Lateralized overgrowth (LO), or segmental overgrowth, is defined as an increase in growth of tissue (bone, muscle, connective tissue, vasculature, etc.) in any region of the body. Some overgrowth syndromes, characterized by both generalized and lateralized overgrowth, have been associated with an increased risk of tumor development. This may be due to the underlying genetic and epigenetic defects that lead to disrupted cell growth and proliferation pathways resulting in the overgrowth and tumor phenotypes. This chapter focuses on the four most common syndromes characterized by LO: Beckwith-Wiedemann spectrum (BWSp), -related overgrowth spectrum (PROS), Proteus syndrome (PS), and hamartoma tumor syndrome (PHTS). These syndromes demonstrate variable risks for tumor development in patients affected by LO, and we provide a comprehensive literature review of all common tumors reported in patients diagnosed with an LO-related disorder. This review summarizes the current data on tumor risk among these disorders and their associated tumor screening guidelines. Furthermore, this chapter highlights the importance of an accurate diagnosis when a patient presents with LO as similar phenotypes are associated with different tumor risks, thereby altering preventative screening protocols.
PubMed: 33392121
DOI: 10.3389/fped.2020.613260