scholarly journals Long-term Healthcare of People with Disorders of Sex Development: Predictors of Pubertal Outcomes of Partial Androgen Insensitivity Syndrome – Authors' Reply

EBioMedicine ◽  
2018 ◽  
Vol 37 ◽  
pp. 31
Author(s):  
Ngee Lek ◽  
Rieko Tadokoro-Cuccaro ◽  
Ieuan Hughes
Keyword(s):  
Disorders Of Sex Development ◽  
Androgen Insensitivity Syndrome ◽  
Androgen Insensitivity ◽  
Sex Development ◽  
Partial Androgen Insensitivity Syndrome

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.

scholarly journals Disorder Of Sex Development : Ambiguous Genitalia, Partial Androgen Insensitivity Syndrome

2018 ◽  
Vol 3 (2) ◽  
pp. 1
Author(s):  
Rajuddin Rajuddin ◽  
Fauzan Fauzan
Keyword(s):  
Disorders Of Sex Development ◽  
External Genitalia ◽  
Ambiguous Genitalia ◽  
Androgen Insensitivity Syndrome ◽  
Gender Assignment ◽  
Androgen Insensitivity ◽  
Sex Development ◽  
Molecular Term ◽  
Congenital Condition ◽  
Partial Androgen Insensitivity Syndrome

Disorders of sex development (DSDs) also known as “intersex” are congenital condition by mismatch in which chromosomal, gonadal and anatomical. One in 4.500 infants is born with abnormalities of External genitalia, and mostly unexplained in molecular term. Androgen Insensitivity Syndrome (AIS) is a common cause of DSDs. Partial Androgen Insensitivity Syndrome (PAIS) is one of three broad subdivided phenotypes of AIS. Typically, characterized by evidence of feminization (i.e., undermasculinization) of the external genitalia at birth, abnormal secondary sexual development in puberty, and infertility in individuals with a 46,XY karyotype. In males characterized, Pais is common to observe a micropenis, hypospadias, and cryptorchidism. Individuals with PAIS that are characterized as women have been observe to have clitoromegaly and a fused labia during puberity . We reported a 13 year old child, with chief complaint primer amenorrhea. The patient admit as a girl but not yet got her menstruation. Patient was referred by Endocrinology Fertility and Reproductive Consultant of OBGYN, that has done Cromosomal and Hormonal analysis. We perform a laparascopy Exploratif and we get no uterus, fallopian tubal and ovarium that are exist. But, we found testis in inguinal canal.  Decision regarding gender assignment are still confronted between patient”s Family and medical staff. The prognosis is depends on the ambiguity of genital, Physical, and Physicosocial adjustment for sex assignment.

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

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.

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

Topical dihydrotestosterone to treat micropenis secondary to partial androgen insensitivity syndrome (PAIS) before, during, and after puberty – a case series

2016 ◽  
Vol 29 (2) ◽  
Author(s):  
David Becker ◽  
Lisa M. Wain ◽  
Yih Harng Chong ◽  
Sonal J. Gosai ◽  
Nina K. Henderson ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Case Series ◽  
Androgen Insensitivity Syndrome ◽  
High Dose ◽  
Long Term Outcomes ◽  
Penile Length ◽  
Androgen Insensitivity ◽  
First Case ◽  
Partial Androgen Insensitivity Syndrome

AbstractX-linked partial androgen insensitivity syndrome (PAIS) causes under-virilization at all stages of development. In two thirds of males, this results in micropenis. Dihydrotestosterone (DHT) is a potent androgen that is critical for male genital development, which when applied topically, has been shown to increase penile length with micropenis of varying etiologies. We present the first case series using topical DHT gel to treat micropenis in 46,XY males with PAIS, before, during, and after puberty.Three related 46,XY males with confirmed p.L712F androgen receptor mutations exhibited varying degrees of micropenis post-surgical correction. They were of pre-pubertal, peri-pubertal and adult ages, respectively. Following baseline clinical and laboratory assessments all completed a 4-month course of daily DHT gel 2.5% (androstanolone) topically to penis (0.3 mg/kg body weight), with monitoring for adverse effects. Primary outcome was change in stretched penile length (SPL) following treatment.Mixed results were obtained following topical DHT therapy. In the pre- and peri- pubertal patients, SPL changed from 2.5 cm to 3.5 cm (+40%), and 3.5 cm to 5.7 cm (+63%), respectively. In the adult patient with 1 year of prior high-dose weekly testosterone therapy, no additional change in SPL was seen. No adverse effects of topical DHT were reported or observed throughout the 4 months of treatment.Topical DHT treatment appears to be a safe and well-tolerated method of virilising micropenis both prior to and during puberty in children with PAIS. Questions remain about long-term outcomes into adulthood, and efficacy in adults with prior lengthy exposure to high-dose testosterone.

Pubertal And Gonadal Outcomes In 46,XY Individuals With Partial Androgen Insensitivity Syndrome Raised As Girls

2021 ◽  
Author(s):  
Guilherme Guaragna-Filho ◽  
Gil Guerra-Junior ◽  
Rieko Tadokoro-Cuccaro ◽  
Ieuan A. Hughes ◽  
Beatriz A. Barros ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumour ◽  
Tanner Stage ◽  
Female Gender ◽  
Androgen Insensitivity Syndrome ◽  
Breast Development ◽  
Androgen Insensitivity ◽  
Stage 4 ◽  
Partial Androgen Insensitivity Syndrome

Abstract Purpose: Although it was common in the 1970s-1990s to assign female gender of rearing to 46,XY infants with limited virilisation of varying etiologies, including those with partial androgen insensitivity syndrome (PAIS), long-term data on outcomes for these individuals are sparse. Therefore, our goal was to use the power of an international registry to evaluate clinical features, surgical management and pubertal data in patients with a molecularly confirmed diagnosis of PAIS who were born before 2008 and were raised as girls. Methods: The current study interrogated the I-DSD Registry for available data on management and pubertal outcomes in individuals with genetically confirmed PAIS who were raised as girls. Results: Among the 11 individuals who fulfilled the key criteria for inclusion the external masculinization score at presentation (EMS) ranged from 2 to 6 (median 5); 7 girls underwent gonadectomy before the age of 9 years, whereas 4 underwent gonadectomy in the teenage years (≥ age 13). Clitoral enlargement at puberty was reported for 3 girls (27%) who presented initially at the time of puberty with intact gonads. In the 9 individuals (82%) for whom gonadal pathology data were provided, there was no evidence of germ cell tumor at median age of 8.1 years. All girls received estrogen replacement and 8/11 had attained Tanner stage 4-5 breast development at last assessment. Conclusion: In general, although it appears that female assignment in PAIS is becoming uncommon, our data provide no evidence to support the practice of prophylactic prepubertal gonadectomy with respect to the risk of a germ cell tumour.

Normal and abnormal sexual differentiation

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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