Leukodystrophy with disorders of sex development due to WT1 mutations

Souza, Paulo Victor Sgobbi de; Badia, Bruno Mattos Lombardi; Silva, Luiz Henrique Libardi; Teixeira, Carlos Alberto Castro; Seneor, Daniel Delgado; Marin, Vitor Dias Gomes Barrios; Farias, Igor Braga; Dias, Renan Braido; Oliveira, Acary Souza Bullé; Pinto, Wladimir B.V.R.

doi:10.1016/j.jns.2018.04.020

Cited by 4 publications

(4 citation statements)

References 12 publications

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“…The details of patients with gonadoblastoma associated with WT1 exonic pathogenic variants reported in the literature (n=13) and the present study (one family) are summarized in Table 2 (4,10,7,11,12,13,14,15,16,17,18,19).The age of presentation ranged from birth to 26 years. Gonadoblastoma was detected earliest at seven months of age, ranging up to 28 years.…”

Section: Resultsmentioning

confidence: 99%

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Exonic WT1 pathogenic variants in 46,XY DSD associated with gonadoblastoma

Arya¹,

Kumar²,

Lila³

et al. 2021

Endocrine Connections

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Objective The literature regarding gonadoblastoma risk in exonic Wilms’ tumor suppressor gene (WT1) pathogenic variants is sparse. The aim of this study is to describe the phenotypic and genotypic characteristics of Asian–Indian patients with WT1 pathogenic variants and systematically review the literature on association of exonic WT1 pathogenic variants and gonadoblastoma. Design Combined retrospective–prospective analysis. Methods In this study, 46,XY DSD patients with WT1 pathogenic variants detected by clinical exome sequencing from a cohort of 150 index patients and their affected relatives were included. The PubMed database was searched for the literature on gonadoblastoma with exonic WT1 pathogenic variants. Results The prevalence of WT1 pathogenic variants among 46,XY DSD index patients was 2.7% (4/150). All the four patients had atypical genitalia and cryptorchidism. None of them had Wilms’ tumor till the last follow-up, whereas one patient had late-onset nephropathy. 11p13 deletion was present in one patient with aniridia. The family with p.Arg458Gln pathogenic variant had varied phenotypic spectrum of Frasier syndrome; two siblings had gonadoblastoma, one of them had growing teratoma syndrome (first to report with WT1). On literature review, of >100 exonic point pathogenic variants, only eight variants (p.Arg462Trp, p.Tyr177*, p.Arg434His, p.Met410Arg, p.Gln142*, p.Glu437Lys, p.Arg458*, and p.Arg458Gln) in WT1 were associated with gonadoblastoma in a total of 15 cases (including our two cases). Conclusions WT1 alterations account for 3% of 46,XY DSD patients in our cohort. 46,XY DSD patients harboring exonic WT1 pathogenic variants carry a small but definitive risk of gonadoblastoma; hence, these patients require a gonadoblastoma surveillance with a more stringent surveillance in those harboring a gonadoblastoma-associated variant.

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Section: Resultsmentioning

confidence: 99%

“…The details of patients with gonadoblastoma associated with WT1 exonic pathogenic variants reported in the literature ( n = 13) and in this study (one family) are summarized in Table 2 ( 4 , 7 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ). The age of presentation ranged from birth to 26 years.…”

Section: Resultsmentioning

confidence: 99%

Exonic WT1 pathogenic variants in 46,XY DSD associated with gonadoblastoma

Arya¹,

Kumar²,

Lila³

et al. 2021

Endocrine Connections

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“…The sole study on the neurologic health of intersex individuals was a case series of 3 individuals with differences in sex development due to a WT1 gene mutation. These individuals presented with hypomyelinating leukodystrophy, leading to a constellation of neurologic symptoms, including gait instability, incontinence, weakness, and seizures …”

Section: Resultsmentioning

confidence: 99%

“…These individuals presented with hypomyelinating leukodystrophy, leading to a constellation of neurologic symptoms, including gait instability, incontinence, weakness, and seizures. 68…”

Section: Neurologic Health Of Intersex Individualsmentioning

confidence: 99%

Sexual and Gender Minority Health in Neurology

et al. 2021

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ittle is known about the neurologic health needs of sexual and gender minority (SGM) individuals (ie, those in the lesbian, gay, bisexual, transgender, and queer [LGBTQ+] spectrum). Understanding an individual's identity is essential for patientcentered communication, which improves patient satisfaction and reduces health disparities. SGM identity directly impacts a variety of neurologic conditions, including epilepsy, 1 dementia, 2 and stroke. 3,4 Neurologists receive little to no dedicated SGM health training, 5 which may lead to conscious or unconscious behaviors that contribute to existing disparities. 6 A 2018 study 3 of US neurologists, for example, found that while most reported comfort in caring for SGM individuals, fewer demonstrated SGM-related medical knowledge. Nearly half of respondents believed that sexual orientation and gender identity had no bearing on the management of neurologic illness. 3 This scoping review seeks to describe the cur-rent state of science in SGM health in neurology to highlight areas of knowledge and gaps to inform future research. MethodsGuided by an experienced medical librarian (E.W.), we developed, tested, and finalized a PubMed search using medical subject headings and keywords with SGM descriptors 7 and neurologic disorders (eAppendix 1 in the Supplement). The disorders were compiled based on clinical expertise, the National Institute of Neurologic Disorders and Stroke website, 8 and prior research. 9 This search was modified for Embase, Web of Science, PsycInfo, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and BIOSIS Previews. IMPORTANCE Little is known about the neurologic health needs of sexual and gender minority (SGM) individuals, and existing research indicates health care disparities for this group. OBJECTIVE To describe the current state of science in SGM neurology and highlight areas of knowledge and gaps to guide future research.EVIDENCE REVIEW All articles published before April 12, 2020, in PubMed, Embase, Web of Science, PsycInfo, CINAHL, and BIOSIS Previews were searched using a search string encompassing SGM descriptors and neurologic disorders. A total of 8359 items were found and entered into EndNote, and 2921 duplicates were removed. A blind title and abstract review was performed followed by full-text review in duplicate, with conflicts settled through consensus, to identify 348 articles eligible for data abstraction. Articles presenting primary data about an identified adult SGM population addressing a clinical neurology topic were included. Descriptive statistics were used for abstracted variables.FINDINGS Of 348 studies, 205 (58.9%) were case reports or series, 252 (72.4%) included sexual minority cisgender men, and 247 (70.9%) focused on HIV. An association was found between autism spectrum disorder and gender dysphoria in 9 of 16 studies (56.3%), and a higher risk of ischemic stroke in transgender women was shown in other studies. Literature in neuroinfectious disease, the most common topic, largely focused on HIV (173 of 200...

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