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BJR Case Reports Mar 2022Proteus syndrome is an extremely rare condition, characterized by progressive asymmetric overgrowth of multiple body tissues. Here, we present two cases of Proteus...
Proteus syndrome is an extremely rare condition, characterized by progressive asymmetric overgrowth of multiple body tissues. Here, we present two cases of Proteus syndrome demonstrating typical clinical and radiological features of Proteus syndrome, in addition to an uncommon fibrolipomatous hamartoma of the sciatic nerve. The first case is a 5-year-old girl who presented with seizures. The patient showed facial dysmorphic features, left head enlargement, kyphoscoliosis, asymmetric overgrowth of the right lower limb, right foot drop, and cribriform connective tissue nevi on the right palm and the right sole. Radiological examinations demonstrated left calvarial hyperostosis, dysplasia of the left cerebral hemisphere, dysregulation of the subcutaneous adipose fat of the body, kyphoscoliosis, and lipoma of the filum terminale. CT of both thighs showed asymmetric soft tissue overgrowth of the right thigh, associated with diffuse enlargement and fatty infiltration of the right sciatic nerve starting from the upper thigh, down to its bifurcation into the tibial and common peroneal nerves. The second case is an 18-year-old girl who presented with left conductive deafness. The patient showed facial dysmorphic features, right head enlargement, asymmetric overgrowth of the right upper limb, kyphoscoliosis, left foot drop, and cribriform connective tissue nevi on the nose and the left foot. Radiological examinations demonstrated right calvarial hyperostosis, left external auditory canal hyperostosis and stenosis, and kyphoscoliosis. CT and MRI of both thighs showed diffuse enlargement of the left sciatic nerve starting from the upper thigh down to the mid-thigh and showing interfascicular adipose tissue proliferation, giving the typical features of nerve lipomatosis.
PubMed: 36177257
DOI: 10.1259/bjrcr.20210153 -
Pediatric Dermatology Jan 2023Linear Cowden nevus, also known as linear PTEN nevus, is a type of epidermal nevus, first described in 2007, which is seen in patients with PTEN hamartoma tumor...
Linear Cowden nevus, also known as linear PTEN nevus, is a type of epidermal nevus, first described in 2007, which is seen in patients with PTEN hamartoma tumor syndrome. It is considered to be a type 2 form of segmental mosaicism, and we suggest that it has certain clinical features that distinguish it from epidermal nevi seen in similar conditions, such as Proteus syndrome. We present a case of linear Cowden nevus in a 4-year-old boy and review the literature.
Topics: Male; Humans; Child, Preschool; Hamartoma Syndrome, Multiple; Nevus, Sebaceous of Jadassohn; Nevus; Mosaicism; PTEN Phosphohydrolase
PubMed: 36151877
DOI: 10.1111/pde.15116 -
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 -
The Turkish Journal of Pediatrics 2022PTEN hamartoma tumor syndrome (PHTS) is an umbrella term including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), PTEN-related Proteus syndrome (PS),...
BACKGROUND
PTEN hamartoma tumor syndrome (PHTS) is an umbrella term including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), PTEN-related Proteus syndrome (PS), and PTEN-related Proteus-like syndrome. One of the disorders in PHTS spectrum, CS is characterized by macrocephaly, mucocutaneous findings, gastrointestinal system (GIS) polyposis and an increased lifetime risk of GIS, breast, thyroid and other cancers.
CASE
In this study, we report an adolescent patient presenting with recurrent life-threatening upper GIS bleeding as a result of hamartomatous polyposis. Genetic studies revealed a known pathogenic nonsense mutation confirming the initial diagnosis of CS.
CONCLUSIONS
Additionally, we describe our therapeutic intervention to improve the patient`s clinical symptoms with sirolimus, which its use is infrequently addressed in the literature for pediatric age group harboring PTEN mutations.
Topics: Adolescent; Child; Hamartoma Syndrome, Multiple; Humans; Melena; PTEN Phosphohydrolase; Sirolimus; Thyroid Gland
PubMed: 36082652
DOI: 10.24953/turkjped.2021.5330 -
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 -
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 -
Postmortem Diagnosis of the Proteus Syndrome by Next Generation Sequencing of Affected Brain Tissue.Academic Forensic Pathology Jun 2022We report a case of a somatic overgrowth syndrome diagnosed at forensic autopsy with the aid of next generation sequencing as Proteus syndrome. Somatic overgrowth...
We report a case of a somatic overgrowth syndrome diagnosed at forensic autopsy with the aid of next generation sequencing as Proteus syndrome. Somatic overgrowth syndromes result from spontaneous somatic mutations that arise early in development and display a mosaic pattern of expression in patient tissues. Due to the temporal and anatomic heterogeneity of these syndromes, phenotypes vary widely, resulting in clinical overlap. Furthermore, the variable ratio of mutated to nonmutated cells in patient tissue can result in low-level mutations that could be missed using Sanger sequencing. Due to these factors, recent literature points to next generation sequencing (NGS) as an adjunct to diagnosis of these rare entities. A male in his fourth decade of life presented to our forensic autopsy service with physical features suggestive of a somatic overgrowth syndrome. Due to the paucity of clinical information accompanying the individual, a definitive diagnosis based on physical characteristics, alone, was not possible. Next generation sequencing of affected formalin-fixed and paraffin-embedded brain tissue confirmed the presence of the variant in (c.49G>A, p.Glu17Lys, in 14.13% of reads) found in Proteus syndrome. To our knowledge, this is the first report of the mosaic variant of detected in brain tissue and the first reported case of a postmortem diagnosis of Proteus syndrome with the aid of NGS. We conclude that NGS can be used as an adjunctive method to support a specific diagnosis among the somatic overgrowth syndromes postmortem in the absence of sufficient clinical history.
PubMed: 35799996
DOI: 10.1177/19253621221097294 -
Pulmonary Circulation Apr 2022Proteus syndrome is a rare progressive multisystem disorder characterized by asymmetric, disproportionate overgrowth of bone, skin, and other tissue types. Molecular...
Proteus syndrome is a rare progressive multisystem disorder characterized by asymmetric, disproportionate overgrowth of bone, skin, and other tissue types. Molecular pathogenesis has been identified as somatic activating mutations of the AKT1 gene. The presentation of Proteus syndrome is exceptionally variable. Respiratory complications include emphysematous lung disease and predisposition to pulmonary emboli, the latter of which is a significant source of mortality. Pulmonary hypertension due to longstanding hypoxic lung disease as well as chronic thromboembolic events has been observed in this population. In contrast, precapillary pulmonary arterial hypertension in the absence of chronic pulmonary emboli and parenchymal lung disease has not been described in the literature on patients with Proteus syndrome. We report such a case in a young patient with Proteus syndrome, reviewing subsequent management and emphasizing the need for a detailed investigation of dyspnea.
PubMed: 35783033
DOI: 10.1002/pul2.12098 -
Children (Basel, Switzerland) Jun 2022. Infantile hemangiomas may have unexpected behavior. Initial regression (spontaneously or drug-induced) may be followed by unexplained recurrences. At this moment,...
. Infantile hemangiomas may have unexpected behavior. Initial regression (spontaneously or drug-induced) may be followed by unexplained recurrences. At this moment, there are no well-established criteria to predict infantile hemangioma reccurrences. . We compared the VEGF pathway gene expression profile for one case of involuting infantile hemangioma versus one case of recurrent proliferative infantile hemangioma using TaqMan Array. . We found ten genes upregulated for both involuting and recurrent proliferative hemangiomas: ACTB, KRAS, MAP2K1, HRAS, NOS3, BAD, HSPB1, HPRT1, GUSB, and CASP9. Thirteen genes were downregulated for both involuting and proliferative hemangiomas: FIGF, ACTG1, GRB2, MAPKAPK2, ACTG2, MAP2K2, MAPK3, HSP90AA1, MAP2K6, NRAS, ACTA1, KDR, and MAPK1. Three genes showed divergent expression between proliferating and involuting hemangiomas. Proliferating hemangioma had MAPK14 and AKT1 gene upregulation and ACTA2 downregulation. Involuting infantile hemangioma was characterized by ACTA2 upregulation and AKT1 and MAPK14 downregulation. . Three genes, AKT1, p38/MAPK14, and ACTA2, were found to have divergent expression in proliferating and involuting infantile hemangiomas. Excepting AKT1, which was mentioned in the last ISSVA classification (strictly related to Proteus Syndrome), none of the other genes were reported. An accurate gene expression profile mapping of infantile hemangiomas together with a gene expression-based hemangioma classification is stringently needed.
PubMed: 35740845
DOI: 10.3390/children9060908 -
Cureus May 2022Proteus syndrome (PS) is a rare overgrowth disease process with only a few hundred cases being reported in the literature. Abnormal formation of the vertebral bodies...
Proteus syndrome (PS) is a rare overgrowth disease process with only a few hundred cases being reported in the literature. Abnormal formation of the vertebral bodies causing scoliosis and spinal stenosis are common features that lead to debilitating pain in these patients. We present a case of a 35-year-old male landscaper with a history of PS causing severe scoliosis and vertebral overgrowth who underwent recurrent sets of multilevel zygapophyseal joint injections for management of his axial back pain. This case illustrates the utility of interventional spinal procedures in patients with progressive pain from PS.
PubMed: 35663702
DOI: 10.7759/cureus.24651