Can Individuals with 47,XYY Karyotypes Exist without Male Phenotype? A Narrative Literature Review and Case Report

Background: The 47,XYY syndrome is a genetic condition found in about 1 in 1000 male children. The expected phenotype is male but could vary greatly. Those with genitourinary abnormalities may also present with microphallus, hypoplastic scrotum, cryptorchidism, hypospadias and mac...

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Main Authors: Marcelo Jones Pires, Laura Coimbra Teixeira, Luise Longo Angeloni, Julia Londero Heleno, Mariana Romano, Marcio Lopes Miranda, Tarsis Paiva Vieira, Mara Sanches Guaragna, Beatriz Amstaldem Barros, Andréa Trevas Maciel-Guerra, Gil Guerra-Junior
Format: Article
Language:English
Published: IMR Press 2025-02-01
Series:Frontiers in Bioscience-Scholar
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Online Access:https://www.imrpress.com/journal/FBS/17/1/10.31083/FBS25251
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author Marcelo Jones Pires
Laura Coimbra Teixeira
Luise Longo Angeloni
Julia Londero Heleno
Mariana Romano
Marcio Lopes Miranda
Tarsis Paiva Vieira
Mara Sanches Guaragna
Beatriz Amstaldem Barros
Andréa Trevas Maciel-Guerra
Gil Guerra-Junior
author_facet Marcelo Jones Pires
Laura Coimbra Teixeira
Luise Longo Angeloni
Julia Londero Heleno
Mariana Romano
Marcio Lopes Miranda
Tarsis Paiva Vieira
Mara Sanches Guaragna
Beatriz Amstaldem Barros
Andréa Trevas Maciel-Guerra
Gil Guerra-Junior
author_sort Marcelo Jones Pires
collection DOAJ
description Background: The 47,XYY syndrome is a genetic condition found in about 1 in 1000 male children. The expected phenotype is male but could vary greatly. Those with genitourinary abnormalities may also present with microphallus, hypoplastic scrotum, cryptorchidism, hypospadias and macroorchidism. This study reports a child with sex ambiguity who possesses an initial 47,XYY karyotype. We also conducted a narrative literature review of 47,XYY individuals and their respective genital phenotype and/or gender identity. Methods: The narrative literature review was performed by searching for “47,XYY” in the PubMed database. All studies published in English, Spanish or Portuguese from January 1960 to January 2024 that contained the term “47,XYY” in the title or abstract were included. Studies that did not describe the genital phenotype and/or gender identity of cases were excluded. We also described the case of a 2-month-old patient with the 47,XYY karyotype and sex ambiguity. Results: Our patient underwent additional karyotype testing, resulting in 47,XYY [30] and another 45,X [2]/47,XYY [98] with mosaicism being confirmed by fluorescent in situ hybridization (FISH) on buccal smears (nuc ish (DXZ1 × 1, DYZ3 × 2)[64/100]/(DXZ1 × 1, DYZ3 × 0)[36/100]. A gonadal biopsy revealed an atrophic testis on the left and a streak gonad on the right, with a final diagnosis of mixed gonadal dysgenesis determined. The narrative review revealed 643 articles, of which 350 met the inclusion criteria. However, we excluded 132 articles because they presented no new cases. We included 138 articles, which presented a series containing less than 10 new cases with the 47,XYY karyotype (total of 327 cases), 58 articles presented 4001 cases and 22 articles presented 75 patients with the 47,XYY karyotype in mosaic with 45,X. For all 4403 analyzed cases, 4354 (98.90%) presented a male phenotype, of which 4322 had the 47,XYY karyotype and 32 had mosaicism with 45,X lineage. A further 23 (0.52%) presented a female phenotype, of which four had the 47,XYY karyotype and 19 had mosaicism with 45,X lineage. In addition, 23 (0.52%) cases presented ambiguous genitalia, of which two had the 47,XYY karyotype and 21 had mosaicism with 45,X lineage. Finally, three (0.06%) cases had undefined phenotypes, all with mosaicism with 45,X lineage. Of the six cases with the 47,XYY karyotype and no male phenotype, one had complete androgen insensitivity syndrome (CAIS), one had lipoid congenital adrenal hyperplasia, two had probable CAIS, and two presented an incomplete diagnostic investigation. Conclusions: A female or ambiguous genital phenotype in an individual with 47,XYY karyotype is uncommon and should alert to the presence of the 45,X lineage or association with other causes of disorder/difference of sex development.
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spelling doaj-art-15a77fca5dad4699b5a472bacf9382d72025-08-20T02:48:54ZengIMR PressFrontiers in Bioscience-Scholar1945-05162025-02-011712525110.31083/FBS25251S1945-0516(24)00118-7Can Individuals with 47,XYY Karyotypes Exist without Male Phenotype? A Narrative Literature Review and Case ReportMarcelo Jones Pires0Laura Coimbra Teixeira1Luise Longo Angeloni2Julia Londero Heleno3Mariana Romano4Marcio Lopes Miranda5Tarsis Paiva Vieira6Mara Sanches Guaragna7Beatriz Amstaldem Barros8Andréa Trevas Maciel-Guerra9Gil Guerra-Junior10Faculty of Medicine, Pontifical Catholic University of Campinas (PUCCAMP), 13083-887 Campinas, Sao Paulo, BrazilInterdisciplinary Group for Studies of Sex Determination and Differentiation (GIEDDS), Faculty of Medical Sciences and Clinical Hospital, State University of Campinas (UNICAMP), 13083-887 Campinas, Sao Paulo, BrazilInterdisciplinary Group for Studies of Sex Determination and Differentiation (GIEDDS), Faculty of Medical Sciences and Clinical Hospital, State University of Campinas (UNICAMP), 13083-887 Campinas, Sao Paulo, BrazilInterdisciplinary Group for Studies of Sex Determination and Differentiation (GIEDDS), Faculty of Medical Sciences and Clinical Hospital, State University of Campinas (UNICAMP), 13083-887 Campinas, Sao Paulo, BrazilInterdisciplinary Group for Studies of Sex Determination and Differentiation (GIEDDS), Faculty of Medical Sciences and Clinical Hospital, State University of Campinas (UNICAMP), 13083-887 Campinas, Sao Paulo, BrazilInterdisciplinary Group for Studies of Sex Determination and Differentiation (GIEDDS), Faculty of Medical Sciences and Clinical Hospital, State University of Campinas (UNICAMP), 13083-887 Campinas, Sao Paulo, BrazilInterdisciplinary Group for Studies of Sex Determination and Differentiation (GIEDDS), Faculty of Medical Sciences and Clinical Hospital, State University of Campinas (UNICAMP), 13083-887 Campinas, Sao Paulo, BrazilInterdisciplinary Group for Studies of Sex Determination and Differentiation (GIEDDS), Faculty of Medical Sciences and Clinical Hospital, State University of Campinas (UNICAMP), 13083-887 Campinas, Sao Paulo, BrazilInterdisciplinary Group for Studies of Sex Determination and Differentiation (GIEDDS), Faculty of Medical Sciences and Clinical Hospital, State University of Campinas (UNICAMP), 13083-887 Campinas, Sao Paulo, BrazilInterdisciplinary Group for Studies of Sex Determination and Differentiation (GIEDDS), Faculty of Medical Sciences and Clinical Hospital, State University of Campinas (UNICAMP), 13083-887 Campinas, Sao Paulo, BrazilInterdisciplinary Group for Studies of Sex Determination and Differentiation (GIEDDS), Faculty of Medical Sciences and Clinical Hospital, State University of Campinas (UNICAMP), 13083-887 Campinas, Sao Paulo, BrazilBackground: The 47,XYY syndrome is a genetic condition found in about 1 in 1000 male children. The expected phenotype is male but could vary greatly. Those with genitourinary abnormalities may also present with microphallus, hypoplastic scrotum, cryptorchidism, hypospadias and macroorchidism. This study reports a child with sex ambiguity who possesses an initial 47,XYY karyotype. We also conducted a narrative literature review of 47,XYY individuals and their respective genital phenotype and/or gender identity. Methods: The narrative literature review was performed by searching for “47,XYY” in the PubMed database. All studies published in English, Spanish or Portuguese from January 1960 to January 2024 that contained the term “47,XYY” in the title or abstract were included. Studies that did not describe the genital phenotype and/or gender identity of cases were excluded. We also described the case of a 2-month-old patient with the 47,XYY karyotype and sex ambiguity. Results: Our patient underwent additional karyotype testing, resulting in 47,XYY [30] and another 45,X [2]/47,XYY [98] with mosaicism being confirmed by fluorescent in situ hybridization (FISH) on buccal smears (nuc ish (DXZ1 × 1, DYZ3 × 2)[64/100]/(DXZ1 × 1, DYZ3 × 0)[36/100]. A gonadal biopsy revealed an atrophic testis on the left and a streak gonad on the right, with a final diagnosis of mixed gonadal dysgenesis determined. The narrative review revealed 643 articles, of which 350 met the inclusion criteria. However, we excluded 132 articles because they presented no new cases. We included 138 articles, which presented a series containing less than 10 new cases with the 47,XYY karyotype (total of 327 cases), 58 articles presented 4001 cases and 22 articles presented 75 patients with the 47,XYY karyotype in mosaic with 45,X. For all 4403 analyzed cases, 4354 (98.90%) presented a male phenotype, of which 4322 had the 47,XYY karyotype and 32 had mosaicism with 45,X lineage. A further 23 (0.52%) presented a female phenotype, of which four had the 47,XYY karyotype and 19 had mosaicism with 45,X lineage. In addition, 23 (0.52%) cases presented ambiguous genitalia, of which two had the 47,XYY karyotype and 21 had mosaicism with 45,X lineage. Finally, three (0.06%) cases had undefined phenotypes, all with mosaicism with 45,X lineage. Of the six cases with the 47,XYY karyotype and no male phenotype, one had complete androgen insensitivity syndrome (CAIS), one had lipoid congenital adrenal hyperplasia, two had probable CAIS, and two presented an incomplete diagnostic investigation. Conclusions: A female or ambiguous genital phenotype in an individual with 47,XYY karyotype is uncommon and should alert to the presence of the 45,X lineage or association with other causes of disorder/difference of sex development.https://www.imrpress.com/journal/FBS/17/1/10.31083/FBS25251disorder of sex development47,xyyturner syndromemixed gonadal dysgenesis
spellingShingle Marcelo Jones Pires
Laura Coimbra Teixeira
Luise Longo Angeloni
Julia Londero Heleno
Mariana Romano
Marcio Lopes Miranda
Tarsis Paiva Vieira
Mara Sanches Guaragna
Beatriz Amstaldem Barros
Andréa Trevas Maciel-Guerra
Gil Guerra-Junior
Can Individuals with 47,XYY Karyotypes Exist without Male Phenotype? A Narrative Literature Review and Case Report
Frontiers in Bioscience-Scholar
disorder of sex development
47,xyy
turner syndrome
mixed gonadal dysgenesis
title Can Individuals with 47,XYY Karyotypes Exist without Male Phenotype? A Narrative Literature Review and Case Report
title_full Can Individuals with 47,XYY Karyotypes Exist without Male Phenotype? A Narrative Literature Review and Case Report
title_fullStr Can Individuals with 47,XYY Karyotypes Exist without Male Phenotype? A Narrative Literature Review and Case Report
title_full_unstemmed Can Individuals with 47,XYY Karyotypes Exist without Male Phenotype? A Narrative Literature Review and Case Report
title_short Can Individuals with 47,XYY Karyotypes Exist without Male Phenotype? A Narrative Literature Review and Case Report
title_sort can individuals with 47 xyy karyotypes exist without male phenotype a narrative literature review and case report
topic disorder of sex development
47,xyy
turner syndrome
mixed gonadal dysgenesis
url https://www.imrpress.com/journal/FBS/17/1/10.31083/FBS25251
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