scholarly journals 45,X/46,XY mosaicism: report on 14 patients from a Brazilian hospital. A retrospective study

2014 ◽  
Vol 132 (6) ◽  
pp. 332-338 ◽  
Author(s):  
Rafael Fabiano Machado Rosa ◽  
Willy Francisco Bartel D'Ecclesiis ◽  
Raquel Papandreus Dibbi ◽  
Rosana Cardoso Manique Rosa ◽  
Patrícia Trevisan ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Turner Syndrome ◽  
Early Recognition ◽  
External Genitalia ◽  
Ambiguous Genitalia ◽  
Referral Hospital ◽  
Clinical Genetics ◽  
Sex Development ◽  
Genital Ambiguity ◽  
The Individual

CONTEXT AND OBJECTIVE: 45,X/46,XY mosaicism, or mixed gonadal dysgenesis, is considered to be a rare disorder of sex development. The aim of our study was to investigate the clinical and cytogenetic characteristics of patients with this mosaicism.DESIGN AND SETTING: A retrospective study in a referral hospital in southern Brazil.METHODS: Our sample consisted of patients diagnosed at the clinical genetics service of a referral hospital in southern Brazil, from 1975 to 2012. Clinical and cytogenetic data were collected from the medical records.RESULTS: Fourteen patients were included in the sample, with ages at the first evaluation ranging from 2 days to 38 years. Nine of them had female sex of rearing and five, male. Regarding the external genitalia, most were ambiguous (n = 10). One patient presented male phenotype and was treated for a history of azoospermia, while three patients presented female phenotype, of whom two had findings of Turner syndrome and one presented secondary amenorrhea alone. Some findings of Turner syndrome were observed even among patients with ambiguous genitalia. None presented gonadal malignancy. One patient underwent surgical correction for genital ambiguity and subsequent exchange of sex of rearing. Regarding cytogenetics, we did not observe any direct correlation between percentages of cell lines and phenotype.CONCLUSIONS: 45,X/46,XY mosaicism can present with a wide variety of phenotypes resulting from the involvement of different aspects of the individual. All these observations have important implications for early recognition of these patients and their appropriate management.

scholarly journals Spectrum of external genital anomalies in disorders of Sex Development at Children Hospital & Institute of Child Health, Lahore, Pakistan

2020 ◽  
Vol 37 (1) ◽  
Author(s):  
Sarah Khan ◽  
Raafea Tafweez ◽  
Areiba Haider ◽  
Muhammad Yaqoob
Keyword(s):  
Child Health ◽  
Wide Spectrum ◽  
Disorders Of Sex Development ◽  
Ambiguous Genitalia ◽  
Delayed Puberty ◽  
Female Sex ◽  
Sex Development ◽  
Mode Of Presentation ◽  
Genital Ambiguity ◽  
Male Sex

Objective: To describe the mode of presentation and frequency of external genital anomalies in disorder of sex development (DSD) Methods: This cross-sectional study was conducted at Children Hospital & Institute of Child Health, Lahore from January to December, 2016 on Children with DSD above 10 years of age. A detailed history and physical examination were done. Positive findings were recorded on a predesigned proforma and analyzed by SPSS 21. Karyotyping on blood samples was done to determine their genetic sex. Results: Out of 83 DSD children, 67% (n=56) were assigned a female sex at birth of which 9% (n=5) had ambiguous genitalia. Male sex at birth was given to 33% (n=27) of which 96% (n=26) had genital ambiguity. Mode of presentation other than ambiguous genitalia were delayed puberty, amenorrhea, hirsuitism, gynaecomastia, cyclic hematuria etc. Clitoromegaly was the main finding in 62.5% (n=5) and micropenis in 45% (n=9). Karyotypic sex of 56 female sex of rearing was 46XX 80% (n=45), 45X0 13% (n=7), XXX 2% (n=1) and 46 XY in 5% (n=3). Karyotypic sex of 27 male sex of rearing was 46XY in 78% (n=21), 46XX in 15% (n=4) and 47XXY in 7% (n=2). Conclusion: Disorders of sex development presented with a wide spectrum of external genital anomalies ranging from clitoromegaly in females to micropenis and hypospadias in males. There was also an extreme diversity in mode of presentation of these cases including pubertal delay, amenorrhea in females and gender confusion disorders. doi: https://doi.org/10.12669/pjms.37.1.2991 How to cite this:Khan S, Tafweez R, Haider A, Yaqoob M. Spectrum of external genital anomalies in disorders of Sex Development at Children Hospital & Institute of Child Health, Lahore, Pakistan. Pak J Med Sci. 2021;37(1):244-249. doi: https://doi.org/10.12669/pjms.37.1.2991 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals Up-to-Date Clinical and Biochemical Workup of the Child and the Adolescent with a Suspected Disorder of Sex Development

2021 ◽  
pp. 279-290 ◽  
Author(s):  
Romina P. Grinspon ◽  
Sebastián Castro ◽  
Rodolfo A. Rey
Keyword(s):  
External Genitalia ◽  
Ambiguous Genitalia ◽  
Diagnostic Approach ◽  
Reproductive Hormone ◽  
Imaging Studies ◽  
Disorder Of Sex Development ◽  
Surgical Exploration ◽  
Sex Development ◽  
Internal Genitalia ◽  
17 Hydroxyprogesterone

Background: The suspicion of a disorder of sex development (DSD) often arises at birth, when the newborn presents with ambiguous genitalia, or even during prenatal ultrasound assessments. Less frequently, the aspect of the external genitalia is typically female or male, and the diagnosis of DSD may be delayed until a karyotype is performed for another health issue, or until pubertal age when a girl presents with absence of thelarche and/or menarche or a boy consults for gynaecomastia and/or small testes. Summary: In this review, we provide a practical, updated approach to clinical and hormonal laboratory workup of the newborn, the child, and the adolescent with a suspected DSD. We focus on how to specifically address the diagnostic approach according to the age and presentation. Key Message: We particularly highlight the importance of a detailed anatomic description of the external and internal genitalia, adequate imaging studies or surgical exploration, the assessment of reproductive hormone levels – especially testosterone, anti-Müllerian hormone, 17-hydroxyprogesterone, and gonadotropins – and karyotyping.

Can Boys Have Turner Syndrome? More than a Question of Semantics

2021 ◽  
pp. 1-8
Author(s):  
Michelle M. Knoll ◽  
Julie Strickland ◽  
Jill D. Jacobson
Keyword(s):  
Clinical Practice ◽  
Turner Syndrome ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Early Recognition ◽  
Sex Development ◽  
Differences Of Sex Development ◽  
Z Scores ◽  
The Mean ◽  
Chromosome Material

Individuals with 45,X mosaicism with Y chromosome material raised as boys are not diagnosed with Turner syndrome, a label restricted to phenotypic females. We sought to determine if boys with 45,X mosaicism had features consistent with Turner syndrome. Twenty-two patients (14 girls, 8 boys) seen in our Differences of Sex Development (DSD) clinic were identified for review. Standardized height (z-scores) by sex of rearing and results of cardiology, renal, audiology, thyroid, and celiac screenings were recorded. All subjects had heights below the mean for sex. Z-scores were not significantly different between boys and girls (<i>p</i> = 0.185). There were no significant differences in the incidence of cardiac anomalies between boys and girls (<i>p</i> = 0.08). Girls were more likely to have additional screenings (<i>p</i> = 0.042), but there were no significant differences in the number of positive screenings between boys and girls (<i>p</i> = 0.332). Patients with 45,X mosaicism raised as boys appear to have features similar to patients with the same karyotype raised as girls. Routine screening of boys following the Turner Syndrome Clinical Practice Guidelines may allow early recognition of comorbidities. Additionally, obtaining karyotypes on boys with short stature or other features of Turner syndrome may identify unrecognized cases of 45,X mosaicism.

scholarly journals Delayed Recognition of Disorders of Sex Development (DSD): A Missed Opportunity for Early Diagnosis of Malignant Germ Cell Tumors

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Remko Hersmus ◽  
Hans Stoop ◽  
Stefan J. White ◽  
Stenvert L. S. Drop ◽  
J. Wolter Oosterhuis ◽  
...  
Keyword(s):  
Germ Cell ◽  
Early Recognition ◽  
Metastatic Cancer ◽  
Germ Cell Tumors ◽  
Disorders Of Sex Development ◽  
Ambiguous Genitalia ◽  
Normal Male ◽  
Testicular Dysgenesis Syndrome ◽  
Sex Development ◽  
Increased Risk

Disorders of sex development (DSD) are defined as a congenital condition in which development of chromosomal, gonadal or anatomical sex is atypical. DSD patients with gonadal dysgenesis or hypovirilization, containing part of the Y chromosome (GBY), have an increased risk for malignant type II germ cell tumors (GCTs: seminomas and nonseminomas). DSD may be diagnosed in newborns (e.g., ambiguous genitalia), or later in life, even at or after puberty. Here we describe three independent male patients with a GCT; two were retrospectively recognized as DSD, based on the histological identification of both carcinomain situand gonadoblastoma in a single gonad as the cancer precursor. Hypospadias and cryptorchidism in their history are consistent with this conclusion. The power of recognition of these parameters is demonstrated by the third patient, in which the precursor lesion was diagnosed before progression to invasiveness. Early recognition based on these clinical parameters could have prevented development of (metastatic) cancer, to be treated by systemic therapy. All three patients showed a normal male 46,XY karyotype, without obvious genetic rearrangements by high-resolution whole-genome copy number analysis. These cases demonstrate overlap between DSD and the so-called testicular dysgenesis syndrome (TDS), of significant relevance for identification of individuals at increased risk for development of a malignant GCT.

scholarly journals Genital Ambiguity and Challenges in Gender Assignment

2020 ◽  
Vol 4 (3) ◽  
Keyword(s):  
World Literature ◽  
Healthcare Professionals ◽  
Age Groups ◽  
External Genitalia ◽  
Northwest Ethiopia ◽  
Primary Amenorrhea ◽  
Gender Assignment ◽  
Sex Assignment ◽  
Genital Ambiguity ◽  
The Individual

This is a case presentation involving two siblings of four and six years of age with female gender identity from a neighboring country with 46,XY DSD and a 20 years old youngster from Northwest Ethiopia with an alleged male sex but with a 46,XX DSD; but definitely all the three with obvious ambiguous external genitalia. The 46XX, DSD with Congenital Adrenal Hyperplasia (CAH) generated more challenges as opposed to the siblings who were diagnosed to have Complete Androgen Insensitivity Syndrome (CAIS). The case presentations are unique as they were referred for sex identification by physicians unlike the usual late complaints of patients with primary amenorrhea or absence of menarche, failure to attain penetrative vaginal sexual intercourse or primary infertility. It was evident that the role of the parents, grandparents, relatives and the healthcare professionals is very much impacting in the sex assignment of the clients, although the final preferential gender choice is made by the individual himself. The atypical external genitalia, contrary to the sex of rearing so far, are the hallmark of the abnormality and source of confusion of the clients under investigations. An early and thorough neonatal physical examination and random checkups of pediatric age groups underscores the complex issues of the subsequent multidisciplinary approach towards the sex assignment. The situations glare the psychosexual and physical development of those involved and the undesirable consequences in their respective families, relatives and their respective societies where beliefs, religion and culture play significant role in the social upbringing of the individual. The main objective of the presentation is to increase the degree of awareness among healthcare professionals of the existence of such congenital anomalies in the communities and is also intended to contribute to the national and world literature.

scholarly journals So, and if it is not congenital adrenal hyperplasia? Addressing an undiagnosed case of genital ambiguity

2021 ◽  
Author(s):  
Reinaldo Luna de Omena Filho ◽  
Reginaldo José Petroli ◽  
Fernanda Caroline Soardi ◽  
Débora de Paula Michelatto ◽  
Taís Nitsch Mazzola ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Treatment Options ◽  
External Genitalia ◽  
Autosomal Recessive Disorder ◽  
Missense Variant ◽  
Ambiguous Genitalia ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Genital Ambiguity ◽  
21 Hydroxylase Deficiency

Abstract The Congenital Adrenal Hyperplasia due to 21 hydroxylase deficiency is the most common cause of genital ambiguity in persons with XX sexual chromosomes. Genital ambiguity among persons with XY sexual chromosomes comprises diverse and rare etiologies. The deficiency of 17-beta-hydroxysteroid dehydrogenase type 3 enzyme (HSD17B3) is a rare autosomal recessive disorder due to functionally altered variants of the HSD17B3 gene. In this disorder/difference of sex development, the conversion of androstenedione into testosterone is impaired. The appearance of external genitalia of 46,XY individuals varies from typically male to almost female. We report on a child presenting severe ambiguous genitalia. Due to access constraints, specialized care did not start until the child was 10 months old. Parents are consanguineous and were born in an area of high isonymy that is a cluster for rare recessive diseases. A new homozygous missense variant c.785G > T was found in exon 10 of the HSD17B3 gene. Researchers-clinicians and researchers-researchers collaborative efforts to elucidate the genetic basis of this disease were critical since this etiologic investigation is not available through the public health system. This case exemplifies the families’ pilgrimage in cases of genital ambiguity due to a rare genetic condition. Recognizing the etiology was the baseline to provide information on prognosis and treatment options, and to shelter family and child doubts and hopes in order to better support their decisions.

scholarly journals Pubertal development in 46,XY patients with NR5A1 mutations

Endocrine ◽  
2021 ◽  
Author(s):  
Isabel Mönig ◽  
Julia Schneidewind ◽  
Trine H. Johannsen ◽  
Anders Juul ◽  
Ralf Werner ◽  
...  
Keyword(s):  
Pubertal Development ◽  
External Genitalia ◽  
Ambiguous Genitalia ◽  
Gene Encoding ◽  
Steroidogenic Factor 1 ◽  
Sex Development ◽  
Sex Assignment ◽  
Internal Genitalia ◽  
Differences Of Sex Development ◽  
Pubertal Transition

Abstract Purpose Mutations in the NR5A1 gene, encoding the transcription factor Steroidogenic Factor-1, are associated with a highly variable genital phenotype in patients with 46,XY differences of sex development (DSD). Our objective was to analyse the pubertal development in 46,XY patients with NR5A1 mutations by the evaluation of longitudinal clinical and hormonal data at pubertal age. Methods We retrospectively studied a cohort of 10 46,XY patients with a verified NR5A1 mutation and describe clinical features including the external and internal genitalia, testicular volumes, Tanner stages and serum concentrations of LH, FSH, testosterone, AMH, and inhibin B during pubertal transition. Results Patients who first presented in early infancy due to ambiguous genitalia showed spontaneous virilization at pubertal age accompanied by a significant testosterone production despite the decreased gonadal volume. Patients with apparently female external genitalia at birth presented later in life at pubertal age either with signs of virilization and/or absence of female puberty. Testosterone levels were highly variable in this group. In all patients, gonadotropins were constantly in the upper reference range or elevated. Neither the extent of virilization at birth nor the presence of Müllerian structures reliably correlated with the degree of virilization during puberty. Conclusion Patients with NR5A1 mutations regardless of phenotype at birth may demonstrate considerable virilization at puberty. Therefore, it is important to consider sex assignment carefully and avoid irreversible procedures during infancy.

scholarly journals Child with ‘46, XX’ disorder of sex development: clues to diagnose aromatase deficiency

2019 ◽  
Vol 12 (12) ◽  
pp. e232575
Author(s):  
Saurav Shishir Agrawal ◽  
Partha Pratim Chakraborty ◽  
Anirban Sinha ◽  
Animesh Maiti
Keyword(s):  
Bone Age ◽  
Ambiguous Genitalia ◽  
Tall Stature ◽  
Polycystic Ovaries ◽  
Disorder Of Sex Development ◽  
Primary Amenorrhoea ◽  
Sex Development ◽  
Genital Ambiguity ◽  
Life Threatening ◽  
History Of

A diagnosis of congenital adrenal hyperplasia (CAH) in a ‘46, XX’ newborn with ambiguous genitalia is like a ‘knee jerk reaction’ of the paediatrician because of its higher frequency and life-threatening consequences if remain undiagnosed and hence untreated. Aromatase deficiency (AD), a rare cause of ‘46, XX’ disorder of sex development, mimics virilising CAH in many aspects; thus, the disease is often overlooked. Diagnosis of AD in women is much easier around puberty due to the presence of primary amenorrhoea, undeveloped breasts, androgen excess and tall stature with eunuchoid proportions. Diagnosing AD with confidence immediately after birth or during early childhood is a challenging task without genetic analysis. In resource-restricted settings, AD remains a diagnosis of exclusion particularly in this age group and history of maternal virilisation, non-progressive genital ambiguity, elevated gonadotrophins (follicle-stimulating hormone >>luteinising hormone), mildly delayed bone age with/without enlarged polycystic ovaries serve as important clues to the underlying AD.

scholarly journals Clinical and cytogenetic characteristics of patients diagnosed with Turner syndrome in a clinical genetics service: cross-sectional retrospective study

2021 ◽  
Author(s):  
Maurício Rouvel Nunes ◽  
Tiago Godói Pereira ◽  
Henry Victor Dutra Correia ◽  
Simone Travi Canabarro ◽  
Ana Paula Vanz ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Turner Syndrome ◽  
Clinical Genetics ◽  
Cross Sectional

scholarly journals Clinical Approach for Evaluation and Manage¬ment of Disorders of Sex Development

2017 ◽  
Vol 1 (3) ◽  
Author(s):  
Najya Abdullah Attia
Keyword(s):  
Genetic Diagnosis ◽  
Tumor Development ◽  
Disorders Of Sex Development ◽  
External Genitalia ◽  
Ambiguous Genitalia ◽  
Rapid Progression ◽  
Clinical Approach ◽  
Sex Development ◽  
Special Approach ◽  
Atypical Development

"It's a boy" and "It's a girl" are words that are heard every second of every day all around the world. However, it is very distressing when the birth attendants are unable to make such a pronouncement because of disorders of sex development (DSD). DSD are congenital conditions associated with an atypical development of chromosomal, gonadal or anatomical sex. Normal sex development progresses in steps from conception to the complete development of the fetal external genitalia; any disturbance in any of these steps can lead to DSD. Ambiguous genitalia are the most common type of DSD and it is a challenging clinical diagnosis for the pediatric endocrinologist. A newborn baby with ambiguous genitalia is often a surprise for both the medical team and the parents, frequently described as an emergency. The condition needs a special approach in terms of counseling the parents appropriately, evaluation and management. The Chicago Conference (2006) recommended new nomenclature and a classification for DSD, as the old nomenclature was confusing for doctors and parents, and sometimes pejorative. The new classification is based on karyotyping and gonadal structure, improving understanding of the underlying pathogenic mechanisms. The rapid progression of genetic diagnosis of DSD using advanced techniques such as next-generation sequencing (NGS) allows more appropriate diagnosis and genetic counseling for families. The focus of the article is a review of normal sex development, DSD classification, clinical approach, genetic assessment, sex assignment, surgical management and risk of germ cell tumor development.

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