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

2012 ◽  
Vol 24 (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.

scholarly journals Androgen insensitivity syndrome in a cohort of Sri Lankan children with 46, XY disorders of sex development

2016 ◽  
Vol 60 (4) ◽  
pp. 139 ◽  
Author(s):  
K.S.H. De Silva ◽  
N.D. Sirisena ◽  
H.K. Wijenayaka ◽  
J.G. Cooray ◽  
R.W. Jayasekara ◽  
...  
Keyword(s):  
Disorders Of Sex Development ◽  
Androgen Insensitivity Syndrome ◽  
Sri Lankan ◽  
Androgen Insensitivity ◽  
Sri Lankan Children ◽  
Sex Development

scholarly journals The Investigation of Quality of Life in 87 Chinese Patients with Disorders of Sex Development

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Chunqing Wang ◽  
Qinjie Tian
Keyword(s):  
Quality Of Life ◽  
Social Relationship ◽  
Disorders Of Sex Development ◽  
Androgen Insensitivity Syndrome ◽  
Chinese Patients ◽  
Sexual Life ◽  
Process Of Care ◽  
Sex Development ◽  
The Difference

Objective. In the process of care for disorders of sex development (DSD), clinical decisions should focus on the long-term quality of life (QOL). We sought to investigate the QOL of patients with DSD in China.Design. Case-control study was carried out.Patients.90 patients of DSD participated in the study. Finally, 87 patients were analyzed including Turner’s syndrome (23), Noonan syndrome (2), androgen insensitivity syndrome (22), testicular regression syndrome (2), congenital adrenal hyperplasia (16), and pure gonadal dysgenesis (22).Measurements. The WHOQOL-BREF questionnaire was chosen for the present investigation. Four domain scores were analyzed independently including physical, psychological, and social relationship and environmental domains.Results. The average age of the DSD group is 22.34 ± 4.97 years, and only 13.79% patients ever had sexual life. The scores of psychological and environmental domains were lower than that of the physical and social relationship domains, but the difference was not significant (P>0.05). Compared with the Chinese urban population, the QOL scores of DSD patients in China were not significantly lower.Conclusions. With proper treatment, including the follow-up and psychological support, the QOL of DSD patients cannot be significantly reduced. For DSD patients, more attention should be paid to the potential psychological and sexual problems.

scholarly journals Genetic Analysis for the Diagnosis of Disorders of Sexual Development in Indonesia

2016 ◽  
Vol 2 (2) ◽  
pp. 44
Author(s):  
Sultana MH Faradz
Keyword(s):  
Sexual Development ◽  
Disorders Of Sex Development ◽  
External Genitalia ◽  
Gonadal Development ◽  
Androgen Insensitivity Syndrome ◽  
Medical Professionals ◽  
Adrenal Hyperplasia ◽  
Disorders Of Sexual Development ◽  
Sex Development

Disorders of sex development (DSD) is defined by congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical, while in clinical practice this term means any abnormality of the external genitalia. DSD patients have been managed by a multidisciplinary gender team in our center as collaboration between Dr. Kariadi province referral hospital and Faculty of Medicine Diponegoro University. Diagnosis should be established by specific physical examination hormonal, chromosomal and DNA studies; and imaging for most of the cases depending on indication.Since 2004 the involvement of molecular and cytogenetic analysis so far can diagnosed many of the DSD cases. Most of the genetically proven cases were Congenital Adrenal hyperplasia, Androgen Insensitivity syndrome and sex chromosomal DSD that lead abnormal gonadal development.  Many of them remain undiagnosed, further testing such as advanced DNA study should be carried out in collaboration with other center in overseas.The novel genes were found in some cases that contributed for the management of DSD.  Information for medical professionals, patients, family members and community about the availability and necessity of DSD diagnosis should be delivered to improve DSD management and patient quality of life.

scholarly journals Disorders of sex development: a study of 194 cases

2018 ◽  
Vol 7 (2) ◽  
pp. 364-371 ◽  
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.

scholarly journals Novel compound variants of the AR and MAP3K1 genes are related to the clinical heterogeneity of androgen insensitivity syndrome

2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Yiping Cheng ◽  
Yan Sun ◽  
Yiming Ji ◽  
Dongqing Jiang ◽  
Guoxin Teng ◽  
...  
Keyword(s):  
Disorders Of Sex Development ◽  
Bioinformatic Analysis ◽  
Androgen Insensitivity Syndrome ◽  
Chinese Patient ◽  
Sequence Alignments ◽  
Systematic Analysis ◽  
Androgen Insensitivity ◽  
Sex Development ◽  
Whole Exome ◽  
Multiple Amino Acid

Abstract Androgen insensitivity syndrome (AIS; OMIM 300068) is the most frequent cause of 46, XY disorders of sex development (DSD). However, the correlation between genotype and phenotype has not been determined. We conducted a systematic analysis of the clinical characteristics, hormone levels, ultrasonography data and histopathology of a 46, XY Chinese patient with AIS. The family was followed up for nearly 8 years. We applied whole-exome sequencing (WES) for genetic analysis of the pedigree and performed bioinformatic analysis of the identified variants. Human embryonic kidney 293T/17 (HEK293T/17) cells were transiently transfected with wild-type or mutant AR and MAP3K1 plasmid. Cell lysates were used to analyze androgen receptor (AR) production. A novel hemizygous AR variant (c.2070C>A, p. His690Glu) and a rare heterozygous MAP3K1 variant (c.778C>T, p. Arg260Cys) were identified by WES in the proband and her mother. Bioinformatic analysis predicted these two variants to be pathogenic. Multiple amino acid sequence alignments showed that p. His690 and p. Arg260 are conserved among various species. His690Glu is a mutation that decreased the AR production, whereas the Arg260Cys mutation increased the AR production. The novel compound variants of the AR and MAP3K1 genes also increased the production of AR protein. Thus, the phenotype of the patient may be caused by defects in both the AR and MAP3K1 signaling pathways. Compound variants of the AR and MAP3K1 genes resulted in a specific phenotype in this patient with AIS. WES might reveal genetic variants that explain the heterogeneity of AIS.

scholarly journals Mobile DNA in Endocrinology: LINE-1 Retrotransposon Causing Partial Androgen Insensitivity Syndrome

2019 ◽  
Vol 104 (12) ◽  
pp. 6385-6390 ◽  
Author(s):  
Rafael Loch Batista ◽  
Katsumi Yamaguchi ◽  
Andresa di Santi Rodrigues ◽  
Mirian Yumie Nishi ◽  
John L Goodier ◽  
...  
Keyword(s):  
Disorders Of Sex Development ◽  
External Genitalia ◽  
Androgen Insensitivity Syndrome ◽  
Gonadal Hormones ◽  
Mobile Dna ◽  
Laboratory Findings ◽  
Cultured Fibroblasts ◽  
Androgen Insensitivity ◽  
Sex Development ◽  
Partial Androgen Insensitivity Syndrome

Abstract Context Androgen insensitivity syndrome (AIS) is the most common cause of disorders of sex development in 46,XY individuals. It is an X-linked condition usually caused by pathogenic allelic variants in the androgen receptor (AR) gene. The phenotype depends on the AR variant, ranging from severe undervirilization (complete AIS) to several degrees of external genitalia undervirilization. Although 90% of those with complete AIS will have AR mutations, this will only be true for 40% of those with partial AIS (PAIS). Objective To identify the genetic etiology of AIS in a large multigenerational family with the PAIS phenotype. Participants Nine affected individuals with clinical and laboratory findings consistent with PAIS and a normal exonic AR sequencing Settings Endocrine clinic and genetic institute from two academic referral centers Design Analysis of whole exons of the AR gene, including splicing regions, was performed, followed by sequencing of the 5′untranslated region (UTR) of the AR gene. Detailed phenotyping was performed at the initial diagnosis and long-term follow-up, and circulating levels of steroid gonadal hormones were measured in all affected individuals. AR expression was measured using RT-PCR and cultured fibroblasts. Results All 46,XY family members with PAIS had inherited, in hemizygosity, a complex defect (∼1100 bp) in the 5′UTR region of the AR surrounded by a duplicated 18-bp sequence (target site duplication). This sequence is 99.7% similar to an active, long, interspersed element present on the X chromosome (AC002980; Xq22.2), which was inserted in the 5′UTR of the AR gene, severely reducing AR expression and leading to PAIS. Conclusion The molecular diagnosis of PAIS remains challenging. The genomic effect of retrotransposon mobilization should be considered a possible molecular cause of AIS and other AR diseases.

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