scholarly journals The Evaluation of Parental Acceptance Towards Children with Sex Chromosomal Disorders of Sex Development Using A Mixed-Method

2021 ◽  
Vol 7 (1) ◽  
pp. 14-21
Author(s):  
Iit Fitrianingrum ◽  
Annastasia Ediati ◽  
Tri Indah Winarni ◽  
Sultana MH Faradz
Keyword(s):  
Mixed Method ◽  
Quantitative Data ◽  
Sex Chromosome ◽  
Disorders Of Sex Development ◽  
External Genitalia ◽  
Parental Acceptance ◽  
Chromosomal Disorders ◽  
Social And Emotional ◽  
Self Blame ◽  
Sex Development

Background: Sex chromosomal Disorder of sex development (DSD) is an atypical abnormality of external genitalia which is mismatched with its sex chromosome traits. The condition of children with DSD affects the dynamics in the family. Parents’ reactions after discovering this health problem vary greatly, such as being in a state of shock, confusion, or self-blame. However, parents’ acceptance is extremely important for better quality of caring, to the healthy social and emotional child development, and to make the best decisions regarding gender assignment.Objective: To describe the acceptance process of parents that have children with sex chromosomes mosaicism DSD.Methods: This study used a mixed-method with a sequential explanatory approach, which was preceded by quantitative data collection followed by qualitative. The total respondents consisted of 14 mothers and 12 fathers of 14 sex chromosome mosaicism DSD patients with XX/XY, X/XY, XYY or XXY variants. Quantitative data were collected using the Indonesian version of the Parental Acceptance-Rejection Questionnaire (PARQ), and interviews were conducted to determine the acceptance process.Results: Most acceptance cases were based on the surgical stage completion in which a higher number of mothers (71.43%) than fathers (50%).Conclusion: It is uneasy for parents to accept children with sex chromosome mosaicisms DSD, hence the fathers struggle more than mothers in accepting those affected. To the best of our knowledge this is the first study in Indonesia to help parent understand and accept their child condition.

scholarly journals Disorders of sex development: a genetic study of patients in a multidisciplinary clinic

2014 ◽  
Vol 3 (4) ◽  
pp. 180-192 ◽  
Author(s):  
Luigi Laino ◽  
Silvia Majore ◽  
Nicoletta Preziosi ◽  
Barbara Grammatico ◽  
Carmelilia De Bernardo ◽  
...  
Keyword(s):  
Sex Chromosome ◽  
Genetic Defect ◽  
Disorders Of Sex Development ◽  
External Genitalia ◽  
Molecular Study ◽  
Testicular Development ◽  
Androgen Synthesis ◽  
Sex Development ◽  
Dna Alterations ◽  
Definition Of

Sex development is a process under genetic control directing both the bi-potential gonads to become either a testis or an ovary, and the consequent differentiation of internal ducts and external genitalia. This complex series of events can be altered by a large number of genetic and non-genetic factors. Disorders of sex development (DSD) are all the medical conditions characterized by an atypical chromosomal, gonadal, or phenotypical sex. Incomplete knowledge of the genetic mechanisms involved in sex development results in a low probability of determining the molecular definition of the genetic defect in many of the patients. In this study, we describe the clinical, cytogenetic, and molecular study of 88 cases with DSD, including 29 patients with 46,XY and disorders in androgen synthesis or action, 18 with 46,XX and disorders in androgen excess, 17 with 46,XY and disorders of gonadal (testicular) development, 11 classified as 46,XX other, eight with 46,XX and disorders of gonadal (ovarian) development, and five with sex chromosome anomalies. In total, we found a genetic variant in 56 out of 88 of them, leading to the clinical classification of every patient, and we outline the different steps required for a coherent genetic testing approach. In conclusion, our results highlight the fact that each category of DSD is related to a large number of different DNA alterations, thus requiring multiple genetic studies to achieve a precise etiological diagnosis for each patient.

Chromosomal Disorders of Sex Development

2018 ◽  
Author(s):  
R. J McKinlay Gardner ◽  
David J Amor
Keyword(s):  
Sexual Development ◽  
De Novo ◽  
Chromosome Abnormality ◽  
Disorders Of Sex Development ◽  
External Genitalia ◽  
Sequential Process ◽  
Chromosomal Disorders ◽  
Sex Development ◽  
Development Proceeds

Chromosomal sex is, for the most part, congruently XX female and XY male. The XX and XY embryo are built on a fundamentally similar outline plan, and only as development proceeds do certain modifications evolve. If at any point in this sequential process some genetic instruction is faulty, inappropriate, or cannot be acted on, the direction of anatomical sexual development may proceed imperfectly or completely incongruently. This chapter reviews the conditions of ambiguous/incomplete/indeterminate development of the internal and external genitalia, where the basis of this is a chromosome abnormality, usually of the X or the Y chromosome. The key role of the SRY male-determining gene in a number of these conditions is noted. The de novo or familial origin of these disorders is discussed, with particular reference to possible risks of recurrence.

scholarly journals STRATEGI COPING ORANGTUA YANG MEMPUNYAI ANAK DENGAN DISORDERS OF SEX DEVELOPMENT KROMOSOM SEKS MOSAIK

2019 ◽  
Vol 17 (2) ◽  
pp. 189
Author(s):  
Iit Fitrianingrum ◽  
Annastasia Ediati ◽  
Sultana MH Faradz
Keyword(s):  
Coping Strategies ◽  
Quantitative Data ◽  
Sex Chromosome ◽  
Disorders Of Sex Development ◽  
Active Coping ◽  
Sex Development ◽  
Brief Cope ◽  
Positive Reframing ◽  
Explanatory Mixed Methods ◽  
And Behavior

This study aims to explore coping strategies used by parents’ of children with mosaic sex chromosome Disorders of Sex Development (DSD). The study applied the sequential explanatory mixed-methods approach that collected quantitative data prior to qualitative data.  Participants were parents of the affected patients diagnosed with DSD with the following karyotype XX/XY, X/XY, XYY, or XXY variants. In total, 14 mothers and 12 fathers of 14 patients with a mosaic sex chromosome DSD participated in this study. We used the Indonesian version of BRIEF COPE to collect quantitative data on coping strategies. Furthermore, an invidual interview was conducted to all participants to elaborate the coping strategies applied by parents in raising their children. The data analysis identified the four most preferred parental coping strategies:  religion, positive reframing, acceptance, and active coping whereas the least preferred coping strategies were humor, substance use, and behavior disengagement. Mothers and fathers in the study did not significantly differ in applying their coping strategies (p>.05). The study suggests health practitioners working with parents of patients affected with mosaic sex chromosome DSD to promote the religion, positive reframing, acceptance, and active coping strategies to facilitate a better acceptance of the affected children.

scholarly journals Characterising SRD5A2 Gene Variants in 37 Indonesian Patients with 5-Alpha-Reductase Type 2 Deficiency

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Nanis S. Marzuki ◽  
Firman P. Idris ◽  
Hannie D. Kartapradja ◽  
Alida R. Harahap ◽  
Jose R. L. Batubara
Keyword(s):  
Autosomal Recessive ◽  
Disorders Of Sex Development ◽  
External Genitalia ◽  
Compound Heterozygous ◽  
Phenotypic Characteristics ◽  
Sex Development ◽  
Srd5a2 Gene ◽  
Diagnostic Approaches ◽  
Autosomal Recessive Condition

The 5-alpha-reductase type 2 deficiency (5ARD2) is an autosomal recessive condition associated with impairment in the conversion of testosterone to dihydrotestosterone. This condition leads to undervirilisation in 46,XY individuals. To date, there have been more than 100 variations identified in the gene responsible for 5ARD2 development (steroid 5-alpha-reductase 2, SRD5A2). However, few studies have examined the molecular characterisation of Indonesian 5ARD2 cases. In the current study, we analysed 37 subjects diagnosed with 46,XY DSD (disorders of sex development) with confirmed variations in the SRD5A2 gene. We examined results from testosterone/dihydrotestosterone (T/DHT) and urinary etiocholanolone/androsterone (Et/An) ratios, as well as from molecular and clinical analyses. Twelve variants in the SRD5A2 gene were identified, and 6 of which were novel, namely, c.34–38delGinsCCAGC, p.Arg50His, p.Tyr136∗, p.Gly191Arg, p.Phe194Ile, and p.Ile253Val variants. Moreover, we determined that 20 individuals contained harmful mutations, while the remaining 17 variants were benign. Those containing harmful mutations exhibited more severe phenotypes with median external genitalia masculinisation scores (EMS) of 3 (1.5–9) and were more likely to be diagnosed at a later age, reared as female, and virilised at pubertal age. In addition, the respective sensitivities for detecting severe 5ARD2 cases using T/DHT (cutoff: 10) and urinary Et/An ratios (cutoff: 0.95) were 85% and 90%, whereas mild cases were only identified with 64.7% and 47.1% sensitivity, respectively. Although we were unable to identify clear correlations between genotypic and phenotypic characteristics in this study, we clearly showed that individuals who were homozygous or compound heterozygous for any of the harmful mutations were more likely to exhibit classic 5ARD2 phenotypes, lower EMS, female assignment at birth, and virilisation during puberty. These results serve to inform the development of improved clinical and molecular 5ARD2 diagnostic approaches, specifically in Indonesian patients.

scholarly journals Shifting syndromes: Sex chromosome variations and intersex classifications

2018 ◽  
Vol 48 (1) ◽  
pp. 125-148 ◽  
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.

Observational study of disorders of sex development in Yaounde, Cameroon

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.

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

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.

scholarly journals Comprehensive Transcriptome Analysis of Hypothalamus Reveals Genes Associated With Disorders of Sex Development in Pigs

2020 ◽  
Author(s):  
Shuwen Tan ◽  
Yi Zhou ◽  
Haiquan Zhao ◽  
Jinhua Wu ◽  
Hui Yu ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Disorders Of Sex Development ◽  
External Genitalia ◽  
Rna Isolation ◽  
Functional Enrichment ◽  
Regulation Mechanism ◽  
Normal Female ◽  
Sex Development ◽  
Mirna Expression Profiles ◽  
Hormone Biosynthesis

Abstract Background Disorders of sex development (DSD) is a chronic autoimmune disease characterized by systemic inflammation, pathological osteogenesis, and endocrine abnormality. However, its genetic etiology remains mostly unknown. In addition, little research focuses on the regulation mechanism from the view of transcriptomics in the hypothalamic-pituitary-gonadal axis (HPGA). The hypothalamus is the integrated center of the HPGA mediating neural, hormonal, and environmental stimulus to sex development. Methods Three XX-DSD (SRY-negative) pig (DSD) and three NF pigs (five months old, 40 kg ± 5 kg) were selected by external genitalia observation and sex determining region Y gene (SRY) detection. The hypothalamus were sampled for RNA isolation, and the mRNA, lncRNA and miRNA expression profiles were analyzed by sequencing. Results A total of 1,258 lncRNAs, 1,086 mRNAs, and 61 microRNAs were found to differentially express in XX-DSD pigs compared with normal female pigs. Many genes in hormone biosynthesis and secretion pathway are significantly up-regulated, and the up-regulation of GNRH1, KISS1 and AVP may be the candidate genes leading the abnormal secretion of GnRH. Next, we predicted the lncRNA-miRNA-mRNA co-expression triplets and constructed three competing endogenous RNA (ceRNA) potentially associated with DSD. Functional enrichment suggested TCONS_00340886, TCONS_00000204 and miR-181a were related to GnRH secretion. Conclusions Our research revealed the first transcriptomic profile in the hypothalamus of XX-DSD pigs and provided new insight in coding and non-coding RNAs that may be associated with DSD in pigs.

scholarly journals MAMLD1 and Differences/Disorders of Sex Development: An Update

2021 ◽  
pp. 1-12
Author(s):  
Mami Miyado ◽  
Maki Fukami ◽  
Tsutomu Ogata
Keyword(s):  
Leydig Cell ◽  
Disorders Of Sex Development ◽  
External Genitalia ◽  
Gene Interactions ◽  
Testicular Function ◽  
Ovarian Dysfunction ◽  
Causative Gene ◽  
Fetal Testis ◽  
Sex Development ◽  
Age Dependent

<i>MAMLD1</i> (alias <i>CXorf6</i>) was first documented in 2006 as a causative gene of 46,XY differences/disorders of sex development (DSD). <i>MAMLD1</i>/<i>Mamld1</i> is expressed in the fetal testis and is predicted to enhance the expression of several Leydig cell-specific genes. To date, hemizygous <i>MAMLD1</i> variants have been identified in multiple 46,XY individuals with hypomasculinized external genitalia. Pathogenic <i>MAMLD1</i> variants are likely to cause genital abnormalities at birth and are possibly associated with age-dependent deterioration of testicular function. In addition, some <i>MAMLD1</i> variants have been identified in 46,XX individuals with ovarian dysfunction. However, recent studies have raised the possibility that <i>MAMLD1</i> variants cause 46,XY DSD and ovarian dysfunction as oligogenic disorders. Unsolved issues regarding MAMLD1 include the association between <i>MAMLD1</i> variants and 46,XX testicular DSD, gene-gene interactions in the development of <i>MAMLD1</i>-mediated DSD, and intracellular functions of MAMLD1.

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