Posted on Authorea 6 Feb 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161263698.83994973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. in igvlhprrpywt ipypoe boshprlsa a oeoegot eurn partial requiring overgrowth bone reconstruc- jaw and debridement ; requiring fibrous canals biopsy-proven ear summarized with both briefly of intel- overgrowths, leg-length cholesteatomas and gingival palsy, tumors , and multiple cerebral tion; osteomas lung of quadriplegic multiple history restrictive a spastic follows: subsequent has as She with disorder, . (PS). scoliosis migration hepatic syndrome impairment, neuronal and Proteus discrepancy, vision for of seizures, notable diagnosis disability, established is lectual previously history with medical female seventeen-year-old Her a is patient Our adolescent tumor, HISTORY PATIENT mass, abdominal is , tumors immature associated syndrome, and Proteus PS of diagnosis cell the germ WORDS ovarian of KEY an review and and A overgrowth PS teratoma. of between immature findings association with known clinical included. adolescent variable first an by the in presents characterized tumor report disorder This complex susceptibility. a tumor is (PS) syndrome Proteus HG200388 grant ABSTRACT NIH by supported was Ours Christopher GRANTS 4 3 2 1 Association. Novel A Underwood Syndrome; S. Proteus John with Adolescent an in Teratoma Immature immature with adolescent an included. in is tumor tumors TITLE cell associated germ and ovarian PS an of susceptibility. and diagnosis tumor PS the and between of overgrowth review association of A findings known clinical first teratoma. variable the by presents characterized disorder report complex This a is (PS) syndrome Proteus Abstract 2021 6, February 2 1 Underwood John A Syndrome; Proteus Association. with Novel Adolescent an in Teratoma Immature nin nvriySho fMdcn,Dprmn fPediatrics of Department Medicine, of School Surgery University of Indiana Department Medicine, of Health School of University Institutes Indiana National Pediatrics Institute, and Research Medicine Genome Internal Human of National Departments Medicine, of School University Indiana ainlIsiue fHealth of Institutes Medicine National of School University Indiana 1 1 hitpe Ours Christopher , hitpe Ours Christopher , 2 atadBurns Cartland R , 2 .Burns R. , 1 1 n ihe Ferguson Michael and , 3 ihe Ferguson J Michael , 4 1 Posted on Authorea 6 Feb 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161263698.83994973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. hntpchtrgniy orc igoi sprmuti Sadcnb icl u otedvriyof diversity criteria diagnostic in its the revised mutation to to a activating due due of an Hayden, 1983) publication difficult 2006), & the al., Biesecker, be Since et (Cohen (L. can 2001). (Wiedemann Biesecker, 2006 1979 and G. 1983 in PS in L. in in 2006; Hayden al Biesecker, paramount and et (L. is presentations Wiedemann Cohen diagnosis over- by by Correct of syndrome heterogeneity. described findings Proteus phenotypic clinical first termed variable was later by and It characterized 1979) susceptibility. disorder tumor complex and and uncommon growth an is syndrome Proteus mass ovarian F´ed´eration de left the Internationale the the by DISCUSSION of IA on stage based considered and ovary. Final teratoma was polycystic staging, 2014). she immature revealed (COG) (Prat, resection, III Group complete classification Grade d’Obst´etrique to (FIGO) Gyn´ecologie indicated Children’s Due et 3A-C). residual per mass no (Figures ovarian I, showed elements right stage / neuroepithelial CT the primitive repeat of four of of where after risk extent pathology clinic, discharged increased oncology was Final in the unremarkable She an later given 2019). disease. had month enoxaparin al., and one well prophylactic et evaluated procedure (Keppler-Noreuil and on the syndrome days tolerated placed mea- Proteus patient mass was in The ovarian she thromboembolism bilateral left mg. venous which resection The 380 requiring weighed during complete obtained. and Intraop- a course, were masses cm washings 5 considered gm. post-operative ovarian x peritoneal was 6,520 11 No weighed large and x and implants 14 nodes. to cm sured lymph peritoneal 13 have enlarged no x identified 26 with to no x intact with 36 found appeared measured was capsule mass ovarian the and right eratively, The took laparotomy 2). encounter exploratory (Figure this oophorectomy as an performed had not She was alkaline testing LDH, pandemic. ALT, COVID coronavirus AST, the unremarkable. bilirubin, before was was normal place urinalysis cystic pelvis ovarian a A large and large including units/mL). with abdomen unremarkable, a the pelvis 35.0 were of of and CMP organs abdomen suggestive and and surrounding AFP, the highly CBC phosphatase on in was effect mass well. mass which cm as Marked 16 attenuation, 1B). noted x tissue Figure 23 1A, soft x (Figure 35 and occasionally teratoma a could calcification, revealed and fat, pelvis scoliosis. needs and components, thoracolumbar she her abdomen severe express exam the was for to neurologic of notable clapped On abdomen CT was or her exam nystagmus. grunted Musculoskeletal quadrants. she and but lower and exotropia commands. distress, and strength, simple bilateral normal acute follow upper for with right no bridge, notable tone nasal the was in low depressed in mobility, exam had was limited best Eye with she appreciated voiding jaw macrocephaly. exam was protuberant mass and and bossing, large On frontal vomiting a included or features with nausea afebrile. Dysmorphic tender no was low- had diffusely systems had She She and of she pain. review distended weeks, normally. her abdominal one-month presentation, recent and stooling a At In cough, following cefdinir. and fatigue, discomfort. of pain fevers, course for and abdominal one-week positive distension chronic a was with abdominal on unsuccessfully progressive acute treated and fevers for grade gain room weight emergency of the period to our presented 10, patient [?] Our was score her PS. Given of 18. PRESENTATION diagnosis of CASE clinical-molecular score a total for a identified criteria for previously , met a identified patient as previously well a as to 13 dition of malfor- score vascular total points), a points), for (5 for (2 overgrowth points) nevi bony & (2 epidermal dyadic phenotype given c.49G Keppler-Noreuil, verrucous the facial PS Burton-Akright, linear points), Using brother for points), (2 Buser, and consanguinity. criteria mation (2 (Sapp, of mother diagnostic tissue/lipoma (2019) history clinical-molecular Biological adipose known dysregulated meets al. no she neck. is et 2019) anterior there Sapp, Biesecker, the and from limited, of criteria is nevus genotype-phenotype history epidermal paternal and healthy, are lipoma; abdominal resection; smercoegot rcsi hne fseicorgans specific of changes cystic or overgrowth asymmetric > pE7)vratfo knbos faetdtsu n ol eev nadtoa points 5 additional an receive would and tissue affected of biopsy skin a from variant (p.E17K) A β- C eeas oml eu A2 a lvtda 0. nt/L(normal units/mL 100.2 at elevated was CA125 serum A normal. also were hCG 2 AKT1 c.49G u oplcsi etoay icse nad- in discussed ovary, left polycystic to due > .1Ko h IKATpathway PI3K-AKT the of p.E17K A AKT1 < Posted on Authorea 6 Feb 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161263698.83994973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. ilie .F,Cle,J . ecra .J,Dvs . clte,M . lo,T . Frazi- . . . A., T. Olson, G., M. Schlatter, M., Davis, J., F. Rescorla, W., Cohen, & J. L., Cullen, D. F., Viljoen, evaluation. Jr., D. patient M., and Billmire, J. diagnosis, differential Graham, criteria, R., 84 diagnostic Weksberg, syndrome: Genet, B., Proteus Med J. (1999). Mulliken, Jr. M., R., syndrome. M. Happle, Proteus G., of L. Biesecker, challenges multifaceted PTEN The (2001). (2001). J. doi:10.1001/jama.285.17.2240 G. management. Harper, L. and . diagnosis Biesecker, . syndrome: . Proteus J., of challenges Shipley, 14 The V., (2006). Murday, L. S., Biesecker, syndrome. Bevan, Proteus R., in Wang, uncommon are A., mutations Martinez, K., Barker, pediatric option in REFERENCES intriguing observed an usually makes response pathway chemotherapy PI3K-AKT-MTOR occur. of of Given recurrence lack inhibitor teratoma. should the an immature and with an treatment of case development , this and immature in ones PS variant with especially AKT1 association argue germline teratomas, known first the collectively immature the ovarian findings report we in These summary, explored In 2019). be al., should syndrome. et Proteus inhibitor (Leoni with AKT miransertib associated an case that inhibitor, , recent with ovarian AKT a treatment serous grade is the that low there pathology, to Additionally, tumor ovarian response 2018). different showed al., with syndrome et AKT1 Proteus Nieuwenhuysen and in GCTs (Van ovarian report activating noted in AKT1 in mutations variants not additionally shown Though AKT1 have should was GCT. of PTEN, ovarian chemotherapy amplification and reports not of PIK3CA but are proteins, 2014), value there pathway al., PS, similar the et mutations, in (Feldman regarding (GCT) found tumors mutations providers cell AKT1 pediatric germ activating testicular the and Given thereafter. adult relapse. surveillance between tumor Comprehensive periodic this debate with National patient the been PS. 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No reuse without permission. — https://doi.org/10.22541/au.161263698.83994973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. 7 Posted on Authorea 6 Feb 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161263698.83994973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. 8 Posted on Authorea 6 Feb 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161263698.83994973/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. 9