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The skin
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
Cavernous haemangiomas of the facial region are usually sporadic, as is the trigeminal area flat vascular naevus of Sturge-Weber syndrome, and the limb angiomas associated with hypertrophy (Klippel-Trenaunay-Weber syndrome). Somatic mutations have been confirmed in vascular endothelial growth factors in some types. Haemangiomatous and lymphangiomatous lesions of the limbs may be associated with hypertrophy and are usually sporadic, although familial cases are described. The usual cause of the Proteus syndrome is somatic mutation in the AKT1 gene. Knowledge of the molecular basis of these disorders is becoming relevant therapeutically and is therefore gaining in clinical importance.
plastic Surgery
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Kangesu Loshan, Jonathan A. Britto, Neil Bulstrode, David Dunaway, Paul Morris, Branavan Sivakumar, Gill Smith, Guy Thorburn
Proteus syndrome is characterised by abnormal overgrowth of bone, blood vessels, lymphatics and soft tissues. It presents in early childhood with lipomas, vascular malformations (capillary, venous and lymphatic malformations), epidermal naevi and often asymmetric overgrowth of limbs and digits. Deep lines and overgrowth of soft tissues on the soles of the feet causing cerebriform thickening is also a characteristic feature (Figs 20.15, 20.16).
Personalized Medicine in Hereditary Cancer Syndromes
Published in II-Jin Kim, Cancer Genetics and Genomics for Personalized Medicine, 2017
Proteus syndrome is not an inherited disorder like the other syndromes mentioned in this chapter; we have, however, included this topic due to similar concept and application of targeted therapy. It is a rare disorder comprising overgrowth and malformations of skin, connective tissue, fat, brain, and other tissues [46, 56]. Major clinical manifestations are irregular, progressive postnasal growth, cutaneous capillary, and venous malformations, monomorphic adenoma of the parotid glands, bilateral ovarian cystadenoma, unilateral cystadenoma, and meningioma [46, 56]. Clinic manifestations overlap with other overgrowth syndromes [56].
Proteus Syndrome: Case Report with Anatomopathological Correlation
Published in Fetal and Pediatric Pathology, 2022
Javier Arredondo Montero, Mónica Bronte Anaut, Juan Carlos López-Gutiérrez
Proteus syndrome, first described in 1979, occurs in 1 per 1,000,000 live newborns. Caused by a somatic mosaicism associated with a heterozygous pathogenic variant in AKT1, the clinical picture consists of an asymmetric and disproportionate overgrowth of bone, skin, adipose tissue, and central nervous system during infancy, becoming progressively disfiguring. Similarly, associations have been established between Proteus syndrome and various neoplastic entities, as well as with thrombosis and pulmonary pathology. Diagnostic criteria include mosaic distribution of lesions, progressive clinical course, and sporadic onset of the disease, as well as the presence of cerebriform connective tissue nevus (Category A), disproportionate limb growth (Category B) and adipose tissue dysregulation (Category C) among others.
Targeting AKT for cancer therapy
Published in Expert Opinion on Investigational Drugs, 2019
Maryam Shariati, Funda Meric-Bernstam
In a phase I study of ARQ092 in subjects with advanced solid tumors, two patients with activating mutation in PIK3CA gene experienced durable partial responses [75] and antitumor activity was observed in patients harboring AKT1-E17K and PIK3CA-H1047R mutations in a phase Ib trial [76]. Results from another phase Ib study of ARQ092 in combination with carboplatin plus paclitaxel demonstrated encouraging clinical activity in ovarian patients. Two ovarian cancer patients, pretreated with carboplatin and paclitaxel, achieved complete response (AKT-E17K mutant) and partial response (unknown AKT mutant) [77]. Ongoing ARQ751 phase I dose escalation study in patients with advanced solid tumors with AKT-1, 2, and 3 genomic alterations, PI3K activating mutations, PTEN-null, and other PTEN actionable mutations demonstrated a manageable safety profile [78]. Interestingly, a non-oncological phase I trial of ARQ092 is also being conducted for the treatment of Proteus syndrome in children and adults patients [79].
Intersections and Clinical Translations of Diabetes Mellitus with Cancer Promotion, Progression and Prognosis
Published in Postgraduate Medicine, 2019
Stanley S. Schwartz, Struan F.A. Grant, Mary E. Herman
As a final example of converging genetic pathways, the Akt2 gene influences diabetes-related traits, and human polymorphisms in Akt2 have been implicated in metabolic syndrome [48]. Mutations in Akt1 and Akt2 also play a major role in cancer. Interestingly, Akt1 has also recently been implicated in the endocrinopathy, Proteus Syndrome (a rare condition characterized by overgrowth of the bones, skin, and other tissues) – and development of benign tumors [46]. Mutations in the gene encoding another member of the PI3K-AKT pathway, PTEN (germline tumor-suppressor phosphatase and tensin homologue), links to constitutive insulin sensitivity and obesity [49] – and to a cancer-predisposition syndrome.