Prenatal diagnosis of sex chromosome aneuploidies and disorders of sex development – a retrospective analysis of 11-year data

AbstractAnalysis of prenatally diagnosed sex chromosome aneuploidies and disorders of sex development (DSDs).This study includes a retrospective data analysis of 46 prenatally detected sex chromosome aneuploidies and one case of 46,XY DSD diagnosed during an 11-year period (2002–2012) at our department.Of the 46 sex chromosome aneuploidies, 29 cases (63.0%) were in the group of a selected population of women according to abnormal first-/second-trimester ultrasound and 17 (37.0%) cases in an unselected population of women who underwent fetal karyotyping because of advanced maternal age. The most common aneuploidy was Turner syndrome in full and mosaic form (50%). Complete androgen insensitivity syndrome was diagnosed in the case of 46,XY DSD.Sex chromosome aneuploidies must be taken into consideration if, in the first or second trimester, abnormalities are revealed on ultrasound, mainly Turner syndrome in full or mosaic form and 47,XYY.

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Normal and abnormal sexual differentiation

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0257 ◽

2020 ◽

pp. 2435-2448

Author(s):

S. Faisal Ahmed ◽

Angela K. Lucas-Herald

Keyword(s):

Sexual Differentiation ◽

Fetal Development ◽

Sex Chromosome ◽

Disorders Of Sex Development ◽

Androgen Insensitivity Syndrome ◽

Dependent Manner ◽

Hormone Production ◽

Concentration Dependent Manner ◽

Sex Development ◽

Partial Androgen Insensitivity Syndrome

Human sex development follows an orderly sequence of embryological events coordinated by a cascade of gene expression and hormone production in a time- and concentration-dependent manner. Underpinning the entire process of fetal sex development is the simple mantra: sex chromosomes (XX or XY) dictate the gonadotype (ovary or testis), which then dictates the somatotype (female or male phenotype). The constitutive sex in fetal development is female. Disorders of sex development (DSD) can be classified into three broad categories based on the knowledge of the karyotype: sex chromosome abnormality (e.g. X/XY, mixed gonadal dysgenesis); XX DSD (e.g. congenital adrenal hyperplasia); XY DSD (e.g. partial androgen insensitivity syndrome).

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Disorders of sex development: a study of 194 cases

Endocrine Connections ◽

10.1530/ec-18-0022 ◽

2018 ◽

Vol 7 (2) ◽

pp. 364-371 ◽

Cited By ~ 9

Author(s):

R Walia ◽

M Singla ◽

K Vaiphei ◽

S Kumar ◽

A Bhansali

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Sex Chromosome ◽

Tertiary Care ◽

Disorders Of Sex Development ◽

Androgen Insensitivity Syndrome ◽

North India ◽

Care Hospital ◽

Adrenal Hyperplasia ◽

Androgen Insensitivity ◽

Sex Development

Objective To study the clinical proﬁle and the management of patients with disorders of sex development (DSD). Design and setting Retrospective study from a tertiary care hospital of North India. Methods and patients One hundred ninety-four patients of DSD registered in the Endocrine clinic of Postgraduate Institute of Medical Education and Research, Chandigarh between 1995 and 2014 were included. Results One hundred and two patients (52.5%) had 46,XY DSD and seventy-four patients (38.1%) had 46,XX DSD. Sex chromosome DSD was identified in seven (3.6%) patients. Of 102 patients with 46,XY DSD, 32 (31.4%) had androgen insensitivity syndrome and 26 (25.5%) had androgen biosynthetic defect. Of the 74 patients with 46,XX DSD, 52 (70.27%) had congenital adrenal hyperplasia (CAH) and eight (10.8%) had ovotesticular DSD. Five patients with sex chromosome DSD had mixed gonadal dysgenesis. Excluding CAH, majority of the patients (90%) presented in the post-pubertal period. One-fourth of the patients with simple virilising CAH were reared as males because of strong male gender identity and behaviour and firm insistence by the parents. Corrective surgeries were performed in twenty patients (20%) of 46,XY DSD without hormonal evaluation prior to the presentation. Conclusion Congenital adrenal hyperplasia is the most common DSD in the present series. Most common XY DSD is androgen insensitivity syndrome, while CAH is the most common XX DSD. Delayed diagnosis is a common feature, and corrective surgeries are performed without seeking a definite diagnosis.

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Rare cases of disorders of sex development (DSD) in adolescents with female phenotype

International Journal of Adolescent Medicine and Health ◽

10.1515/ijamh.2012.027 ◽

2012 ◽

Vol 24 (2) ◽

Cited By ~ 2

Author(s):

Jenara Kristesashvili ◽

Mariam Chipashvili ◽

Teimuraz Jorbenadze ◽

Donald E. Greydanus

Keyword(s):

Turner Syndrome ◽

Physiological Stress ◽

Disorders Of Sex Development ◽

Androgen Insensitivity Syndrome ◽

Point Of View ◽

Androgen Insensitivity ◽

Female Phenotype ◽

Sex Development

Abstract Background: Disorders of sex development (DSD) belong to uncommon pathologies; in addition, there are especially rare forms, such are ovotesticular disorders (OT), Turner syndrome and early malignisation of intraabdominal located gonads in the cases of androgen insensitivity syndrome. Objective: In this article we present four rare cases of DSD in female phenotype adolescents: two cases of ovotesticular DSD with 46,XX and 46,XY karyotypes; one familial case of androgen insensitivity syndrome (AIS) with early malignancy (19-year-old) of intra-abdominally-located testicle in older siblings, and a case of spontaneous menstruation in a patient with Turner syndrome and mosaic karyotype 45,X/47,XXX. Rare cases of DSD are connected with diagnostic and management difficulties and so description of each such case and collection of data in this field is very important from a scientific, as well as a practical, point of view. Determination of prognosis and adequate management of each individual patient are also essential. Study of this issue is especially sensitive in the case of adolescent patients in order to avoid physiological stress, to reduce health risks and to improve quality of life.

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Comparison between two inhibin B ELISA assays in 46,XY testicular disorders of sex development (DSD) with normal testosterone secretion

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2017-0351 ◽

2018 ◽

Vol 31 (2) ◽

pp. 191-194

Author(s):

Guilherme Guaragna-Filho ◽

Antônio Ramos Calixto ◽

Georgette Beatriz De Paula ◽

Laurione Cândido De Oliveira ◽

André Moreno Morcillo ◽

...

Keyword(s):

Disorders Of Sex Development ◽

Androgen Insensitivity Syndrome ◽

Inhibin B ◽

Enzyme Linked Immunosorbent Assay ◽

Specific Patient ◽

Testosterone Secretion ◽

Sex Development ◽

Interclass Correlation ◽

Bland Altman Method ◽

Partial Androgen Insensitivity Syndrome

Abstract Background: Inhibin B is a hormone produced by the Sertoli cells that can provide important information for the investigation of disorders of sex development (DSD) with 46,XY karyotype. The aim of this study is to compare two enzyme-linked immunosorbent assay (ELISA) assays for dosage of serum inhibin B in patients with 46,XY DSD with normal testosterone secretion. Methods: Twenty-nine patients with 46,XY DSD and normal testosterone secretion (partial androgen insensitivity syndrome [PAIS] [n=8]; 5α-reductase deficiency [n=7] and idiopathic 46,XY DSD [n=14]) were included. Molecular analysis of the AR and SRD5A2 genes were performed in all patients and the NR5A1 gene analysis in the idiopathic group. Measurements of inhibin B were performed by two second-generation ELISA assays (Beckman-Coulter and AnshLabs). Assays were compared using the interclass correlation coefficient (ICC) and the Bland-Altman method. Results: ICC was 0.915 [95% confidence interval (CI): 0.828–0.959], however, a discrepancy was observed between trials, which is more evident among higher values when analyzed by the Bland-Altman method. Conclusions: It is recommended to perform the inhibin B measurement always using the same ELISA kit when several evaluations are required for a specific patient.

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Shifting syndromes: Sex chromosome variations and intersex classifications

Social Studies of Science ◽

10.1177/0306312718757081 ◽

2018 ◽

Vol 48 (1) ◽

pp. 125-148 ◽

Cited By ~ 13

Author(s):

David Andrew Griffiths

Keyword(s):

Lived Experience ◽

Classification System ◽

Consensus Statement ◽

Sex Chromosome ◽

Disorders Of Sex Development ◽

Current Drive ◽

Medical Community ◽

New Classification ◽

Sex Development

The 2006 ‘Consensus statement on management of intersex disorders’ recommended moving to a new classification of intersex variations, framed in terms of ‘disorders of sex development’ or DSD. Part of the rationale for this change was to move away from associations with gender, and to increase clarity by grounding the classification system in genetics. While the medical community has largely accepted the move, some individuals from intersex activist communities have condemned it. In addition, people both inside and outside the medical community have disagreed about what should be covered by the classification system, in particular whether sex chromosome variations and the related diagnoses of Turner and Klinefelter’s syndromes should be included. This article explores initial descriptions of Turner and Klinefelter’s syndromes and their subsequent inclusion in intersex classifications, which were increasingly grounded in scientific understandings of sex chromosomes that emerged in the 1950s. The article questions the current drive to stabilize and ‘sort out’ intersex classifications through a grounding in genetics. Alternative social and historical definitions of intersex – such as those proposed by the intersex activists – have the potential to do more justice to the lived experience of those affected by such classifications and their consequences.

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Observational study of disorders of sex development in Yaounde, Cameroon

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2019-0458 ◽

2020 ◽

Vol 33 (3) ◽

pp. 417-423

Author(s):

Suzanne Ngo Um Sap ◽

Ritha Mbono Betoko ◽

Martine Etoa Etoga ◽

Pierre Yves Mure ◽

Yves Morel ◽

...

Keyword(s):

Sex Chromosome ◽

Disorders Of Sex Development ◽

Central Africa ◽

Main Diagnosis ◽

Pediatric Endocrinology ◽

Endocrine Society ◽

Sex Development ◽

Mother And Child ◽

Study Population ◽

Sub Saharan

AbstractIntroductionAccording to the current classification of the Lawson Wilkins Pediatric Endocrine Society (LWPES) and the European Society for Pediatric Endocrinology (ESPE) of Disorders of Sex Development (DSD), etiologies vary around the world. Ethnic or genetic diversity probably explains this variability. We therefore conducted the present study on etiologies of DSDs in a country from central Africa.MethodsWe carried out an observational retrospective study at the Pediatric Endocrinology Unit of the Mother and Child Centre of the Chantal Biya Foundation in Yaounde, Cameroon from May 2013 to December 2019. All patients diagnosed with a DSD were included, and incomplete files excluded.ResultsWe included 80 patients diagnosed with DSD during the study period. The 46,XX DSD were the most frequent in our study population (n = 41, 51.25%), with congenital adrenal hyperplasia (CAH) as the main diagnosis. The 46,XY DSD accounted for 33.75% and sex chromosome DSD group represented 15% of the study population.ConclusionsDSDs are not an exceptional diagnosis in a Sub-Saharan context. 46,XX DSD are the most prevalent diagnosis in our setting. The diagnosis of all these affections is late compared to other centers, justifying advocacy for neonatal screening of DSDs in our context.

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Long-term healthcare of people with disorders of sex development: Predictors of pubertal outcomes of partial androgen insensitivity syndrome

EBioMedicine ◽

10.1016/j.ebiom.2018.10.026 ◽

2018 ◽

Vol 37 ◽

pp. 29-30 ◽

Cited By ~ 1

Author(s):

Maki Fukami

Keyword(s):

Disorders Of Sex Development ◽

Androgen Insensitivity Syndrome ◽

Androgen Insensitivity ◽

Sex Development ◽

Partial Androgen Insensitivity Syndrome

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Etiology and Clinical Presentation of Disorders of Sex Development in Kenyan Children and Adolescents

International Journal of Endocrinology ◽

10.1155/2019/2985347 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9

Author(s):

Prisca Amolo ◽

Paul Laigong ◽

Anjumanara Omar ◽

Stenvert Drop

Keyword(s):

Children And Adolescents ◽

Sex Chromosome ◽

Clinical Laboratory ◽

Molecular Genetic ◽

Management Strategies ◽

Disorders Of Sex Development ◽

Ambiguous Genitalia ◽

Molecular Genetic Analysis ◽

High Rate ◽

Sex Development

Objective. The purpose of this study was to describe baseline data on etiological, clinical, laboratory, and management strategies in Kenyan children and adolescents with Disorders of Sex Development (DSD). Methods. This retrospective study included patients diagnosed with DSD who presented at ages 0–19 years from January 2008 to December 2015 at the Kenyatta National (KNH) and Gertrude’s Children’s (GCH) Hospitals. After conducting a search in the data registry, a structured data collection sheet was used for collection of demographic and clinical data. Data analysis involved description of the frequency of occurrence of various variables, such as etiologic diagnoses and patient characteristics. Results. Data from the records of 71 children and adolescents were reviewed at KNH (n = 57, 80.3%) and GCH (n = 14, 19.7%). The mean age at the time of diagnosis was 2.7 years with a median of 3 months. Thirty-nine (54.9%) children had karyotype testing done. The median age (IQR) of children with reported karyotypes and those without was 3.3 years (1.3–8.9) and 8.3 years (3.6–12.1), respectively (p=0.021). Based on karyotype analysis, 19 (48.7%) of karyotyped children had 46,XY DSD and 18 (46.2%) had 46,XX DSD. There were two (5.1%) children with sex chromosome DSD. Among the 71 patients, the most common presumed causes of DSD were ovotesticular DSD (14.1%) and CAH (11.3%). Majority (95.7%) of the patients presented with symptoms of DSD at birth. The most common presenting symptom was ambiguous genitalia, which was present in 66 (93.0%) patients either in isolation or in association with other symptoms. An ambiguous genitalia was initially observed by the patient’s mother in 51.6% of 62 cases despite the high rate (84.7%) of delivery in hospital. Seventeen (23.9%) of the cases had a gender reassignment at final diagnosis. A psychologist/psychiatrist or counselor was involved in the management of 23.9% of the patients. Conclusion. The commonest presumed cause of DSD was ovotesticular DSD in contrast to western studies, which found CAH to be more common. Investigation of DSD cases is expensive and needs to be supported. We would have liked to do molecular genetic analysis outside the country but financial challenges made it impossible. A network for detailed diagnostics in resource-limited countries would be highly desirable. There is a need to train health care workers and medical students for early diagnosis. Psychological evaluation should be carried out for all patients at diagnosis and support given for families.

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THE ROLE OF UROLOGISTS IN MANAGEMENT OF DISORDERS OF SEX DEVELOPMENT

Indonesian Journal of Urology ◽

10.32421/juri.v19i1.49 ◽

2012 ◽

Vol 19 (1) ◽

Author(s):

Ilham Wahyudi ◽

Irfan Wahyudi ◽

Kanadi Sumadipradja ◽

Jose RL Batubara ◽

Arry Rodjani

Keyword(s):

Multidisciplinary Team ◽

Disorders Of Sex Development ◽

Androgen Insensitivity Syndrome ◽

Therapeutic Management ◽

Gender Assignment ◽

Disorder Of Sex Development ◽

Sex Development ◽

Diagnostic Management ◽

One Year

Objective: To evaluate disorder of sex development (DSD) profile at Cipto Mangunkusumo Hospital (RSCM), the management profile, and the role of urologist on diagnostic and therapeutic management. Material & method: We retrospectively collected data from medical record of all DSD cases managed by pediatric endocrinologist, urologist, obstetric gynaecologist at RSCM from January 2002 up to December 2009. 2006 IICP criteria was used as classification. The management profile and the role of urologist were evaluated. Results: there were 133 DSD cases with the majority of cases was congenital adrenal hyperplasia (CAH) followed by androgen insensitivity syndrome (AIS). Most of the cases were diagnosed before one year old and other on pubertal period. Karyotyping, laboratory examination, ultrasonography, genitography, uretrocystoscopy, kolposcopy, diagnostic laparascopy were performed as diagnostic management. Gender assignment was performed by multidisciplinary team. Masculinizing surgery, feminizing surgery, and gonadectomy was done as therapeutic management. Conclusion: The majority case on RSCM’s DSD profile was CAH. The management was performed by multidisciplinary team. Gender assignment decision should be based upon thorough diagnostic evaluation. The urologist has important role on diagnostic and therapeutic management. Keywords: Disorder of sex development, diagnostic management, gender assignment, therapeutic management, urologist.

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