Severe gynaecological involvement in Proteus Syndrome

Sévérino-Freire, Maëlla; Maza, A.; Kuentz, Paul; Duffourd, Yannis; Faivre, Laurence; Brazet, Edith; Chassaing, Nicolas; Mery-Lemarche, Eliane; Vabres, P.; Mazereeuw‐Hautier, J.

doi:10.1016/j.ejmg.2018.08.003

Cited by 3 publications

(6 citation statements)

References 18 publications

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“…In two prenatal cases of Proteus syndrome harboring AKT1 variants reported previously, brain anomalies were present: HMEG/MEG with VM, dysmorphic lateral ventricles, PMG and/or heterotopia, as well as dysmorphic features associated with (H)MEG 31,54,55 . Yet, with this combination of anomalies, PROS is much more likely, since, in our experience, PIK3CA variants are about 100 times more common than are AKT1 variants 9,24,56 . In addition, extensive LM are suggestive of CLOVES/KTS rather than Proteus syndrome.…”

Section: Discussionmentioning

confidence: 80%

Clinical and molecular data in cases of prenatal localized overgrowth disorder: major implication of genetic variants in PI3K‐AKT‐mTOR signaling pathway

Bourgon

Carmignac

Sorlin

et al. 2022

Ultrasound in Obstet & Gyne

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diagnosis of congenital abnormality and suspicion of a localized overgrowth disorder (LOD) suggestive of genetic variants in the PI3K-AKT-mTOR signaling pathway. MethodsWe analyzed retrospectively data obtained between 1 January 2013 and 1 May 2020 from fetuses with brain and/or limb overgrowth referred for molecular diagnosis of PI3K-AKT-mTOR pathway genes by next-generation sequencing (NGS) using pathological tissue obtained by fetal autopsy. We also assessed the diagnostic yield of amniotic fluid. ResultsDuring the study period, 21 subjects with LOD suspected of being secondary to a genetic variant of the PI3K-AKT-mTOR pathway were referred for analysis. Of these, 17 fetuses had brain overgrowth, including six with isolated megalencephaly (MEG) and 11 with hemimegalencephaly (HMEG). Of the six with MEG, germline variants were identified in four cases, in either PIK3R2, AKT3 or MTOR, and a postzygotic PIK3R2 variant was found in the other two cases. Of the 11 with HMEG, a postzygotic PIK3CA variant was found in three fetuses with extracerebral features of PIK3CA-related overgrowth spectrum, and in seven fetuses with isolated

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Section: Discussionmentioning

confidence: 80%

Clinical and molecular data in cases of prenatal localized overgrowth disorder: major implication of genetic variants in PI3K‐AKT‐mTOR signaling pathway

Bourgon

Carmignac

Sorlin

et al. 2022

Ultrasound in Obstet & Gyne

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“…Although Proteus syndrome was already diagnosed and the patient had been frequently evaluated in the inpatient setting for pulmonary complications, she had never had a gynecologic evaluation due to the rare association of the syndrome with gynecologic manifestations. No typical gynecologic involvement in Proteus syndrome is well known; cases in the literature have reported associated ovarian serous cystadenomas [ 6 ], ovarian cysts [ 9 ], and uterine leiomyomas [ 10 ]. In the case of a patient with a prolapsing uterus with an irregular contour and multiple tissue-like growths, differential diagnosis typically includes fibroids, neoplasm, and polyps.…”

Section: Discussionmentioning

confidence: 99%

“…One of the hallmark features of Proteus syndrome is asymmetric and uneven growth of tissue, which is due to the presence of the Pglu17lys AKT1 mutation involving connective tissue [ 1 ]. In the literature, there are only 13 cases with gynecologic involvement in Proteus syndrome [ 6 ]. Most of these patients were diagnosed before the age of 11 years [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…In the literature, there are only 13 cases with gynecologic involvement in Proteus syndrome [ 6 ]. Most of these patients were diagnosed before the age of 11 years [ 6 ]. Among gynecologic manifestations of Proteus syndrome, ovarian serous cystadenoma is the most often reported (in 4 of the 13 cases) [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…Most of these patients were diagnosed before the age of 11 years [ 6 ]. Among gynecologic manifestations of Proteus syndrome, ovarian serous cystadenoma is the most often reported (in 4 of the 13 cases) [ 6 , 7 ]. In most of the reported cases, the gynecologic manifestations of Proteus syndrome ultimately required surgical intervention [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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A rare gynecologic presentation of proteus syndrome: A case report

Abouzeid

Buck

Haikal

et al. 2022

Case Reports in Women's Health

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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.

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Postmortem Diagnosis of the Proteus Syndrome by Next Generation Sequencing of Affected Brain Tissue

Baker¹,

Glen²,

Wilson³

et al. 2022

Academic Forensic Pathology

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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 AKT1 (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 AKT1 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.

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Severe gynaecological involvement in Proteus Syndrome

Cited by 3 publications

References 18 publications

Clinical and molecular data in cases of prenatal localized overgrowth disorder: major implication of genetic variants in PI3K‐AKT‐mTOR signaling pathway

Clinical and molecular data in cases of prenatal localized overgrowth disorder: major implication of genetic variants in PI3K‐AKT‐mTOR signaling pathway

A rare gynecologic presentation of proteus syndrome: A case report

Postmortem Diagnosis of the Proteus Syndrome by Next Generation Sequencing of Affected Brain Tissue

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