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Cureus Apr 2022The phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a collection of diseases stemming from mutations in the PTEN tumor suppressor gene and is...
The phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a collection of diseases stemming from mutations in the PTEN tumor suppressor gene and is characterized by variable expressivity and abnormal overgrowth in multiple body systems. Its clinical manifestations include, but are not limited to, lipomas, limb overgrowth, dermatologic lesions, and malignancy. The infrequency of occurrence and broadness of clinical presentation has made the diagnosis and differentiation of different subtypes of PHTS challenging. This case report describes a five-year-old patient with a history of autism and macrocephaly who presented to the emergency department with right lower quadrant (RLQ) pain concerning for appendicitis. A physical exam was significant for right leg hemihypertrophy. Imaging ruled out appendicitis but diagnosed two large right-sided abdominal lipomas. The patient was discharged with the recommendation to pursue genetic testing given the physical exam findings and history. Following confirmation of a PTEN tumor suppressor gene mutation, the patient continued to have increased frequency of abdominal pain, developed vision changes, and was diagnosed with a benign follicular thyroid nodule. Hemihypertrophy, recurrent unilateral lipomas, and a confirmed PTEN mutation are consistent with a diagnosis of Proteus-like syndrome, a rare subtype of PHTS.
PubMed: 35582557
DOI: 10.7759/cureus.24135 -
Orphanet Journal of Rare Diseases Apr 2022Clinical outcome assessments are important tools for measuring the natural history of disease and efficacy of an intervention. The heterogenous phenotype and difficult...
BACKGROUND
Clinical outcome assessments are important tools for measuring the natural history of disease and efficacy of an intervention. The heterogenous phenotype and difficult to quantity features of Proteus syndrome present challenges to measuring clinical outcomes. To address these, we designed a global clinical assessment for Proteus syndrome, a rare mosaic overgrowth disorder. The Clinical Gestalt Assessment (CGA) aims to evaluate change over time in this phenotypically diverse disorder.
RESULTS
We gathered paired serial photographs and radiographs obtained at 12-to-36-month intervals from our natural history study of Proteus syndrome. The chronologic order of each set was blinded and presented to clinicians familiar with overgrowth disorders. They were asked to determine the chronologic order and, based on that response, rate global clinical change using a seven-point scale (Much Worse, Worse, Minimally Worse, No Change, Minimally Improved, Improved, Much Improved). Following a pilot, we tested the inter-rater reliability of the CGA using eight cases rated by eight clinicians. Raters identified the correct chronologic order in 53 of 64 (83%) of responses. There was low inter-rater variance and poor to moderate reliability with an intraclass correlation coefficient of 0.46 (95% CI 0.24-0.75). The overall estimate of global change was Minimally Worse over time, which is an accurate reflection of the natural history of Proteus syndrome.
CONCLUSIONS
The CGA is a tool to evaluate clinical change over time in Proteus syndrome and may be a useful adjunct to measure clinical outcomes in prospective therapeutic trials.
Topics: Humans; Outcome Assessment, Health Care; Phenotype; Proteus Syndrome; Reproducibility of Results
PubMed: 35461279
DOI: 10.1186/s13023-022-02325-6 -
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 -
Reviews in Cardiovascular Medicine Mar 2022Endovascular therapeutic hypothermia (ETH) reduces the damage by ischemia/reperfusion cell syndrome in cardiac arrest and has been studied as an adjuvant therapy to...
BACKGROUND
Endovascular therapeutic hypothermia (ETH) reduces the damage by ischemia/reperfusion cell syndrome in cardiac arrest and has been studied as an adjuvant therapy to percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI). New available advanced technology allows cooling much faster, but there is paucity of resources for training to avoid delays in door-to-balloon time (DTB) due to ETH and subsequently coronary reperfusion, which would derail the procedure. The aim of the study was to describe the process for the development of a simulation, training & educational protocol for the multidisciplinary team to perform optimized ETH as an adjunctive therapy for STEMI.
METHODS AND RESULTS
We developed an optimized simulation protocol using modern mannequins in different realistic scenarios for the treatment of patients undergoing ETH adjunctive to PCI for STEMIs starting from the emergency room, through the CathLab, and to the intensive care unit (ICU) using the Proteus® Endovascular System (Zoll Circulation Inc™, San Jose, CA, USA). The primary endpoint was door-to-balloon (DTB) time. We successfully trained 361 multidisciplinary professionals in realistic simulation using modern mannequins and sham situations in divisions of the hospital where real patients would be treated. The focus of simulation and training was logistical optimization and educational debriefing with strategies to reduce waste of time in patient's transportation from different departments, and avoiding excessive rewarming during transfer. Afterwards, the EHT protocol was successfully validated in a trial randomizing 50 patients for 18 minutes cooling before coronary recanalization at the target temperature of 32 ± 1.0 ∘C or PCI-only. A total of 35 patients underwent ETH (85.7% [30/35] in 90 ± 15 minutes), without delays in the mean door-to-balloon time for primary PCI when compared to 15 control group patients (92.1 minutes versus 87 minutes, respectively; = 0.509).
CONCLUSIONS
Realistic simulation, intensive training and educational debriefing for the multidisciplinary team propitiated feasible endovascular therapeutic hypothermia as an adjuvant therapy to primary PCI in STEMI.
CLINICALTRIALS
gov: NCT02664194.
Topics: Humans; Hypothermia, Induced; Myocardial Infarction; Percutaneous Coronary Intervention; ST Elevation Myocardial Infarction; Time Factors; Treatment Outcome
PubMed: 35345271
DOI: 10.31083/j.rcm2303104 -
Case Reports in Orthopedics 2022In the setting of below-knee amputation, compartment syndrome is a rare complication. Early clinical symptoms of an acute compartment syndrome following below-knee...
In the setting of below-knee amputation, compartment syndrome is a rare complication. Early clinical symptoms of an acute compartment syndrome following below-knee amputation can mimic or be masked by postoperative pain management. We present the case of a 38-year-old male with a significant past medical history of Proteus syndrome who underwent an elective transtibial below-knee amputation. Following surgery, the patient had extensive postoperative pain and high pain medication requirements and returned to the operating room for irrigation and debridement due to suspicion of an infection. Upon return to the operating room to manage the infection, the necrotic tissue was discovered and removed which had developed due to a suspected missed acute compartment syndrome. The necrotic tissue secondary to the compartment syndrome subsequently resulted in infection. Multiple irrigation and debridement procedures were performed to further manage the infection, and ultimately, the patient was deemed stable for discharge. Acute compartment syndrome (ACS) following below-knee amputation (BKA) is a rarely documented but critical complication. This case describes the unique setting in which a compartment syndrome can be masked due to postoperative pain management and infection. Orthopedic surgeons should be aware of the varying risk factors and presentations of an acute compartment syndrome (ACS) as it can occur and is a devastating complication.
PubMed: 35237457
DOI: 10.1155/2022/1256823 -
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 -
Case Reports in Women's Health Jan 2022Proteus syndrome is a genetic condition with an estimated incidence of less than one in a million. This condition is sporadic and presents as progressive, mosaic...
Proteus syndrome is a genetic condition with an estimated incidence of less than one in a million. This condition is sporadic and presents as progressive, mosaic overgrowth of different tissues. Clinical manifestations are diverse, with the reported involvement of lungs, skin, blood cells, the nervous system and bones. Gynecologic manifestations have rarely been reported in the literature. This case is the first to be reported in the literature of a woman with Proteus syndrome diagnosed in her prepubertal years and presenting at 34 years old with a cervical mass protruding from the vagina. The patient sought medical intervention only after the prolapse was advanced and symptomatic. Management of this case was surgical and consisted of vaginal hysterectomy, with vaginal suspension.
PubMed: 34917488
DOI: 10.1016/j.crwh.2021.e00373 -
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 -
Cureus Oct 2021Macrodystrophia lipomatosa (MDL) is a rare congenital overgrowth syndrome characterised by inadvertent proliferation of all the mesenchymal elements resulting in...
Macrodystrophia lipomatosa (MDL) is a rare congenital overgrowth syndrome characterised by inadvertent proliferation of all the mesenchymal elements resulting in localised gigantism. Herein, we present an eight-month-old female child, who presented to us with a history of gradual enlargement of both lower limbs along with the toes which was noticed by the parents a few days after birth. There was no history of trauma, pain or skin changes. Physical examination revealed unusual hypertrophy of both feet and toes. It was non-tender with no evidence of oedema or bruit over the swelling. X-ray of lower limbs revealed bony hypertrophy and overgrowth of all the bones with increased soft tissue shadow of bilateral foot. On ultrasound evaluation of the lower limbs, there was increased soft tissue in both dorsal and plantar aspect of bilateral foot without any vascular malformation. To characterise the swelling better, magnetic resonance imaging was warranted which revealed accumulation of excessive fat in the subcutaneous tissue without discernible capsule. Fibrous strand within the fat in bilateral feet, both in the plantar and dorsal aspect (more in plantar aspect), was seen. Core tissue biopsy was performed which showed abundant adipose tissue dispersed in mesh-like fibrous tissue and infiltrating the dermal connecting, suggestive of macrodystrophia lipomatosa. Currently, patient is advised for corrective surgery. Clinicians should be aware of these atypical presentations of MDL to differentiate it from other causes of local gigantism like fibrolipohamartoma (FLH) of nerve sheath, lymphangiomatosis, hemangiomatosis, Proteus syndrome, Klippel-Trenaunay syndrome and neurofibromatosis 1 as they differ in management and outcome.
PubMed: 34820241
DOI: 10.7759/cureus.18986 -
Cold Spring Harbor Molecular Case... Dec 2021Proteus syndrome is a rare overgrowth disorder caused by postzygotic activating variants in Individuals may develop a range of skin, bone, and soft tissue overgrowth...
Proteus syndrome is a rare overgrowth disorder caused by postzygotic activating variants in Individuals may develop a range of skin, bone, and soft tissue overgrowth leading to functional impairment and disfigurement. Therapy for this disorder is limited to supportive care and surgical intervention. Inhibitors of AKT, originally designed as cancer therapeutics, are a rational, targeted pharmacologic strategy to mitigate the devastating morbidity of Proteus syndrome. 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. At completion of a planned 48-wk phase 1 pharmacodynamic study, the individual derived sufficient benefit that the study was amended to permit continued use and assess the long-term safety of miransertib. The treatment has been well-tolerated with mild treatment-attributed side effects including headache, transient hyperglycemia, and transient elevations of aspartate aminotransferase, alanine aminotransferase, and bilirubin. The patient has experienced sustained improvement of pain and slowed growth of bilateral plantar cerebriform connective tissue nevi. This case report supplements the data from our prior study extending those findings out to 5 years. It shows that at the doses used, miransertib has a favorable safety profile and durable benefit of improving symptoms of pain and slowing progression of overgrowth in Proteus syndrome in a single individual. Although an uncontrolled single report cannot prove safety or efficacy, these data lend support to the encouraging preliminary data of our prior phase 1 pharmacodynamic study.
Topics: Aminopyridines; Humans; Imidazoles; Male; Proteus Syndrome; Proto-Oncogene Proteins c-akt
PubMed: 34649967
DOI: 10.1101/mcs.a006134