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Differential diagnosis formulated at completion of the clinical examination.

Differential diagnosis formulated at completion of the clinical examination.

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O sexo cromossômico é estabelecido na fertilização pela presença de um cromossomo X ou Y. O desenvolvimento dos sexos masculino e feminino passa, num primeiro momento, pela especialização das gônadas em testículos ou ovários; os demais processos decorrem de efeitos secundários provocados pelos hormônios por elas produzidos. As etapas de determinaçã...
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We report the case of a female patient suffering from a 46,XY disorder of sexual development (DSD) with complete gonadal dysgenesis and Wiedemann-Steiner Syndrome (WDSTS). The coexistence of these 2 conditions has not yet been reported. Using whole exome sequencing and comparative genome hybridization array, we identified a de novo MLL/KMT2A gene n...
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To review the common clinical presentations, investigations and final diagnosis of children presenting with genital ambiguity. Retrospective search of the Royal Children's Hospital, Brisbane, Australia, medical records and personal medical database of one of the authors (MJT) between 1982 and 1999. Fifty-one children aged 0.1-14 (mean 3.9) years we...

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... Intersexuality has a complex etiology, being the result of different mutations of specific genes involved in the process of sexual differentiation, which leads to different molecular events. 2 The advances in identifying the molecular basis of abnormal sex and the ethical issues related to management of these conditions led to a review of their nomenclature and classification. The term "disorders of sexual development" (DSD) is proposed instead of intersex, referring to congenital conditions in which development of chromosomal, gonadal or anatomical sex is atypical. ...
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Authors report a case of a 6-year-old child with syndromic 46, XY disorder of sexual development. From the birth patient was assigned female. Physical examination showed dysmorphic features and ambiguous external genitalia. Cytogenetic analysis of cultured peripheral blood lymphocytes revealed a male karyotype. The result of the chromosomal investigation showing male genetic sex, together with the ambivalent aspect of the external genitalia and gonads that are exclusively testes led to the diagnosis of 46, XY disorder of sexual development. The clinical management will help the child and the family deal effectively with this condition A multidisciplinary approach to this problem involving pediatricians, specialists in the field of endocrinology, genetics, surgery and psychiatry is necessary in order to reach a prompt and correct diagnosis and treatment.
... Each year, approximately 1 in 3,000 infants is born with a disorder of sexual differentiation (DSD). One of the many challenges, and often a stressful one, particularly for parents , is determining the sex assignment1234. Because of the paucity of studies on outcomes and decision-making criteria that lead to satisfactory sex assignment, practice guidelines for sex assignment have not yet been established. Several clinical guidelines by our group [4] and others [5] have been suggested. ...
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To catalogue patients with DSD and to assess the concordance of genotype and phenotype with sex assignment at birth compared to sex assignment before and following assessment by a Gender Medicine Team (GMT) at one institution, as an initial step in formulating standardized guidelines for management of these conditions. After obtaining IRB approval, a retrospective chart review was conducted patients seen in the Gender Medicine Clinic (GMC) between 2006–2009 at Texas Children’s Hospital (TCH), Houston, Texas. McNemar’s test and Kappa agreement provided associations of various factors with sex assignment at birth prior to GMT assessment and after GMT assessment. Forty-seven patients seen in the GMC with confirmed DSD. Forty-seven patients met the inclusion criteria. The mean age of the patients at the time of GMT evaluation was 9.1+/−6.1 years; 61.7% had male karyotype, and 38.3% had female karyotype; 51.1% had a male external phenotype, 42.6% had a female external phenotype, and 6.4% had phenotypic ambiguity. Sex assignment was concordant with genotype and phenotype in 63.8% and 86.4%, respectively of cases at the time of birth and in 76.6% and 97.7%, respectively, of cases after assessment by GMT. Long-term outcomes are needed to establish standardized practice guidelines for decision-making.
... Differentiation of the male external genitalia requires normal androgen production and adequate response of target tissues during fetal life (1). Male external genital malformation is related to either insufficient testosterone production by fetal testis or partial androgen resistance of target organs (2)(3)(4). ...
... Male external genital malformation is related to either insufficient testosterone production by fetal testis or partial androgen resistance of target organs (2)(3)(4). The etiology of undervirilization in males includes gonadal dysgenesis, defects in androgen biosynthesis, and, most frequently, androgen resistance (1). ...
... All patients with undermasculinization should be first investigated for the basal or post-human chorionic gonadotropin (hCG) test level of plasma testosterone: a low plasma testosterone level tends to indicate testicular dysgenesis or testosterone biosynthesis defects; conversely, normal/high plasma testosterone orients toward the diagnosis of partial androgen insensitivity syndrome (PAIS) (1,(4)(5)(6). ...
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46,XY disorders of sex differentiation (46,XY DSD) can be due to a testis determination defect, an androgen biosynthesis defect, or androgen resistance (complete or partial androgen insensitivity syndrome (PAIS), or 5α reductase deficiency). We aimed to evaluate the impact of a prenatal contamination by environmental xenoestrogens in 'idiopathic' PAIS-like phenotype. We investigated 28 newborn/infant males with 46,XY DSD, normal androgen production, and no androgen receptor or steroid-5αR type II enzyme (SRD5A2) gene mutations. To exclude other genetic defects, we sequenced the steroidogenic factor 1 (SF1) and mastermind-like domain-containing 1 (MAMLD1) genes, which were recently found to be associated with the PAIS-like phenotype. Parents were interviewed about their environmental/occupational exposure to endocrine disrupting chemicals (EDCs) before/during the patients' fetal life. Total estrogenic bioactivity of patient serum was analyzed by ultrasensitive bioassay. All the patients had normal SF1 sequence and one patient showed a double polymorphism of MAMLD1. Eleven (39.3%) of the 28 patients had reported parental fetal exposure to EDCs. The mean estrogenic bioactivity in these 11 patients with fetal EDC exposure (6.65 ± 8.07 pg/ml) versus 17 cases without contamination (1.27 ± 0.34 pg/ml) and controls (1.06 ± 0.44 pg/ml; P<0.05) was elevated. Our results indicate that the 'idiopathic' PAIS-like phenotype may in some cases be related to EDC contamination during fetal life.
... During foetal life, the differentiation of the male external genitalia requires normal androgen production and adequate response of target tissues. Androgen secretion by the foetal testis is controlled by human chorionic gonadotropins (hCG) during the first trimester and by foetal pituitary hormones later in development (Sultan et al., 2004). The development of micropenis is thus related to either insufficient testosterone production by the foetal testis or the partial androgen resistance of the target organ (Lee et al., 1980;Singh & Glassberg, 1993;Elder, 1998). ...
... In this study, we deliberately focused on boys with isolated micropenis and normal testosterone production, that is, patients with undervirilization who potentially present some degree of androgen resistance, such as partial androgen insensitivity or 5aR deficiency (Sultan et al., 2004). Among these patients with isolated micropenis, two presented a mutation of the AR gene. ...
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Micropenis is defined as a stretched penile length of less than 2-2.5SD for age. Aetiologies include hypogonadotropic hypogonadism, testicular dysgenesis, defects in testosterone synthesis, androgen resistance [5α-reductase (5αR) deficiency or partial androgen insensitivity] and other rare causes like growth hormone GH deficiency. Often, the cause remains unknown. The aim of this study was to determine whether isolated micropenis with normal plasma testosterone could hide a molecular defect in the androgen pathway. Twenty-six boys with isolated micropenis were included in this study. All of them had 46,XY karyotype, normal luteinizing hormone and follicle-stimulating hormone and a normal plasma testosterone response to human chorionic gonadotropin testing. Androgen receptor (AR), 5αR and steroidogenic factor 1 (SF1) genes were sequenced. A mutation in the AR gene was found in two patients, and a new mutation in the SF1 gene was found in one patient who was the only one to have a low level of inhibin B (InhB). This is the first report of isolated micropenis as a revealing symptom of AR and SF1 mutations. Anti-Mullerian hormone and InhB should thus be evaluated in patients with isolated micropenis, even when plasma testosterone is in the normal range. Detection of gene mutations is helpful for diagnosis, treatment and genetic counselling for probands.
Chapter
Sexual differentiation goes through three successive phases, including genetic sex determination (genetic sex), primary sexual differentiation, or male/female gonadal development (gonadal sex) and secondary sexual differentiation, or male/female genitalia development (genital sex). Besides, environmental factors can influence sexual and psychological identity. Anomalies in each of these phases can lead to pathologies of sexual development, in which the normal progression of events is disrupted, resulting in disorders of sexual development (DSD), which include genital ambiguity, that is clinical conditions of external genitalia which do not have the typical appearance of male or female genitalia. The age of presentation of DSD varies from the neonatal age to late adolescence, but most of the cases are observed in the perinatal period. As appropriate gender assessment is necessary for healthy physical and psychological development of the child, an early diagnosis must be elicited, to allow proper management, that is medical and/or surgical treatment, that can be necessary since the neonatal age or along life, and also possible preventive strategies, in terms of sexual function, fertility and risk of tumor development. The role of imaging in evaluating the anatomical condition is of paramount importance in the assessment of gender. Ultrasonography (US) is the first-line imaging modality in the definition of the internal and external reproductive organs. US examination can be easily performed and should include, besides the pelvis and the scrotum, also the inguinal, perineal, renal, and adrenal regions, because of the possible involvement or the presence of associated anomalies. Magnetic resonance imaging (MRI), with multiplanar acquisitions and tissue characterization, allows better spatial and structural definition of the internal organs, especially when US fails to identify and/or define exactly the Müllerian structures and the gonads. MRI should include the pelvis and the perineum and also the urinary tract. Genitography and voiding cystourethrography are used to determine internal ductal anatomy. Endoscopic examination (genitoscopy) can often outpace genitography and provide more detailed assessment of the genital tract. The management of DSDs with ambiguous genitalia represents a great challenge for clinicians and a multidisciplinary team is advisable, including at least specialists in endocrinology, surgery and/or urology, radiology, clinical psychology/psychiatry, nursing and neonatology. Clinicians and care givers should be really sensitive to the complex and subjectively unique physical, psychological, social and behavioral situation of DSD patients.
Article
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We report a case of an infant with syndromic 46,XY disorder of sexual development. The subject was born at term, to unrelated parents with no relevant medical history. At birth the infant was assigned female. Physical examination showed dysmorphic features and ambiguous external genitalia. Cytogenetic analysis of cultured peripheral blood lymphocytes revealed a male karyotype. The result of the chromosomal investigation showing male genetic sex, together with the ambivalent aspect of the external genitalia (Prader IV) and gonads that are exclusively testes led to the diagnosis of 46,XY disorder of sexual development. The clinical management will help the child and the family deal effectively with this condition A multidisciplinary approach to this problem involving pediatricians, specialists in the field of endocrinology, genetics, surgery and psychiatry is necessary in order to reach a prompt and correct diagnosis and treatment.
Article
Children born with disorders of sexual differentiation (DSD) pose numerous challenges for the parents, family, and treating physicians. The pediatrician is usually the first medical contact for newborns with DSD or for toddlers and children who present with DSD at a later time. Several years ago, we formed a Gender Medicine Team (GMT) at Baylor College of Medicine and Texas Children’s Hospital (TCH) to explore and evaluate the most appropriate management strategies, which had long been a matter of concern and contention. Subsequently, the GMT, composed of experts in the fields of endocrinology, ethics, genetics, gynecology, psychology, pediatric surgery, and urology, formed a Task Force to evaluate the information available from our own experiences and from reviews of the literature. Utilizing the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system to assess the evidence and recommendations, the Task Force developed a consensus statement for clinical management of DSD and for making appropriate sex assignments.
Article
Exposure to endocrine-disrupting chemicals (EDCs) has been suggested to contribute to the increasing trends of external genital malformation in male newborns. In Northeastern Brazil, the poor sanitary conditions found in the favelas encourage the widespread use of pesticides. This 2-year study of a total birth cohort of full-term male newborns in the regional hospitals of Campina Grande (Paraíba, Brazil) sought to (1) accurately establish for the first time the incidences of neonatal male genital malformations, (2) investigate the endocrine and genetic aetiologies of these malformations, and (3) evaluate their associations with possible prenatal exposure to EDCs. A total of 2710 male newborns were explored for cryptorchidism, hypospadias and micropenis. Cases were referred to the Pediatric Endocrine Clinic for endocrine and genetic investigations, and all parents were interviewed about their environmental/occupational exposure to EDCs before/during pregnancy by paediatric endocrinologists using a detailed questionnaire. We observed 56 cases of genital malformation (2.07%), including 23 cryptorchidism (0.85%), 15 hypospadias (0.55%), and 18 micropenis (0.66%). All cases exhibited normal/subnormal testosterone production and none presented androgen receptor or 5α-reductase gene mutation. More than 92% of these newborns presented foetal contamination by EDCs, as their mothers reported daily domestic use of pesticides (i.e., DDT) and other EDCs. Most of these undervirilized male newborns presented additional EDC contamination, as 80.36% of the mothers and 58.63% of the fathers reported paid or unpaid work that entailed the use of pesticides and other EDCs before/during pregnancy for the mothers and around the time of fertilization for the fathers. The high rate of micropenis in our population associated with an elevated percentage of parental environmental/occupational exposure to EDCs before/during pregnancy indicates that foetal contamination may be a risk factor for the development of male external genital malformation.
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To investigate nursing students' knowledge, attitude and readiness to work for clients with sexual health concerns and to identify strategies to help students develop as they take up their role in sexual health-related care. There is an increasing global demand for improving sexual health. A better understanding of nursing students' attitude and readiness to work for clients with sexual health concerns is the beginning of this endeavour. The need to explore strategies for developing competent health care practitioners is timely. A cross-sectional survey. Nursing students (n = 377) studying in pre- and post-registration programmes were surveyed at a university in Hong Kong using a questionnaire with open- and closed-ended questions about their knowledge, attitude and self-perception on readiness to work for clients with sexual health concerns. Students' knowledge of sexual health was satisfactory. They were positive in acknowledging the nursing role in sexual health care, but hesitant in taking up an active role in practice. Students' readiness to participate in related activities was below satisfactory. Their perception of inadequate knowledge, feelings of anxiety, worries about colleagues' and clients' possible adverse responses and inadequate exemplars were major factors affecting their readiness. This paper also highlighted some important learning areas and strategies that could help in enhancing students' knowledge and confidence in sexual health care practices. Improving the educational programme and clinical practice for nursing students is necessary but may not be adequate. Valuing the affective aspect of education, formal recognition of this extended role and advancing related education to a post-experience level would also benefit the development of sexual health care. Preparing more mentors as exemplars, inviting clinicians and managers as partners in sexual health-related care would help nursing students to work efficiently for clients with sexual health concerns.