Pediatric Urologists of Canada (PUC) 2021 position statement: Differences of sex development (AKA disorders of sex development)

Differences/disorders of sex development (DSD) are a heterogeneous group of congenital conditions, resulting in discordance between an individual's sex chromosomes, gonads, and/or anatomic sex. The management of a newborn with suspected 46,XY DSD remains challenging. Newborns with 46,XY DSD may present with several phenotypes ranging from babies with atypical genitalia or girls with inguinal herniae to boys with micropenis and cryptorchidism. A mismatch between prenatal karyotype and female phenotype is an increasing reason for presentation. Gender assignment should be avoided prior to expert evaluation and possibly until molecular diagnosis. The classic diagnostic approach is time and cost-consuming. Today, a different approach may be considered. The first line of investigations must exclude rare life-threatening diseases related to salt wasting crises. Then, the new genetic tests should be performed, yielding increased diagnostic performance. Focused imaging or endocrine studies should be performed on the basis of genetic results in order to reduce repeated and invasive investigations for a small baby. The challenge for health professionals will lie in integrating specific genetic information with better defined clinical and endocrine phenotypes and in terms of long-term evolution. Such advances will permit optimization of counseling of parents and sex assignment. In this regard, society has significantly changed its attitude to the acceptance and expansion beyond strict binary male and female sexes, at least in some countries or cultures. These management advances should result in better personalized care and better long-term quality of life of babies born with 46,XY DSD.

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Differences of sex development (DSD)

Paediatric Endocrinology and Diabetes ◽

10.1093/med/9780198786337.003.0011 ◽

2020 ◽

pp. 335-350

Author(s):

Gary Butler ◽

Jeremy Kirk

Keyword(s):

Gonadal Dysgenesis ◽

Gonad Development ◽

Disorders Of Sex Development ◽

Androgen Insensitivity Syndrome ◽

Trisomy 13 ◽

Delayed Puberty ◽

Genetic Syndromes ◽

Sex Development ◽

Differences Of Sex Development ◽

21 Hydroxylase Deficiency

• Embryology: the gonad is initially bipotential. • The testes develop under active control of SRY and other genes. Disorders of sex development (DSDs) are classified according to the karyotype: • 46,XY DSD (incomplete masculinization of a male fetus): ◦ The commonest cause is androgen insensitivity syndrome (AIS): ■ mutations in androgen receptor (AR) gene on X chromosome in complete forms ■ alterations in androgen binding in partial forms. ◦ Abnormalities of testosterone synthesis and conversion, may be: ■ isolated, e.g. 17β‎HSD, 5α‎RD ■ occur in association with defects in steroid biosynthesis, e.g. StAR, 3β‎HSD. • Pure 46,XY gonadal dysgenesis (Swyer syndrome): ◦ phenotype unambiguously female; may present with delayed puberty ◦ Müllerian structures are present but only streak gonads are seen. • Mixed gonadal dysgenesis: ◦ usually asymmetrical, e.g. ovary/streak gonad or ovotestis ◦ karyotype is 45,X/46,XY or 46,XX/46,XY. • Pure 46,XX gonadal dysgenesis: ◦ absent puberty in a phenotypically normal female ◦ intact Müllerian structures but streak ovaries; normal genitalia. • 46,XX DSD (masculinization of a female fetus): ◦ the commonest cause is congenital adrenal hyperplasia, with the vast majority (>90%) due to 21-hydroxylase deficiency (21OHD). • Ovotesticular DSD is rare: ◦ aetiology is unknown, and karyotype usually 46,XX ◦ asymmetrical gonad development; ovary and testis or ovotestis. • DSD may also be part of other genetic syndromes, e.g. Antley–Bixler, Smith–Lemli–Opitz, trisomy 13. • Management requires careful evaluation and counselling, working as part of a multidisciplinary team.

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Sex Dimorphism of Birth Weight and Length: Evidence Based on Disorders of Sex Development

10.21203/rs.3.rs-508679/v1 ◽

2021 ◽

Author(s):

Debora Stabile Romero Amais ◽

Tainara Emilia Rodrigues da Silva ◽

Beatriz Amstalden Barros ◽

Juliana Gabriel Ribeiro de Andrade ◽

Sofia Helena Valente de Lemos-Marini ◽

...

Keyword(s):

Birth Weight ◽

Disorders Of Sex Development ◽

Normal Karyotype ◽

Negative Influence ◽

Positive Influence ◽

Sex Dimorphism ◽

Cross Sectional ◽

Sex Development ◽

Xy Gonadal Dysgenesis ◽

Differences Of Sex Development

Abstract The aim of this study was to verify the influence of Y chromosome and intrauterine androgens production/action on birth weight and length of children with Disorders/Differences of Sex Development (DSD). This was a cross-sectional and retrospective study. Cases of Turner syndrome (TS), complete (XX and XY), mixed (45,X/46,XY) and partial (XY) gonadal dysgenesis (GD), complete (CAIS) and partial (PAIS) androgen insensitivity syndromes and XX and XY congenital adrenal hyperplasia (CAH) were included. Such conditions were grouped according to karyotype and to intrauterine production/action of androgens. The sample consisted of 293 cases, 50 with TS, 28 mixed GD, 117 CAH (49 XY and 68 XX), 18 CAIS, 10 PAIS, 30 partial GD, 10 XY and 30 XX complete GD. Birth weight and length were lower in TS and mixed GD when compared to XY and XX. In turn, patients with increased androgen production/action (117 cases) had higher birth weight and length when compared to those with absent (108 cases) and decreased (68 cases) production/action. It was observed a negative influence of the 45,X/46,XY karyotype in birth weight and a positive influence of increased androgen production/action. Regarding birth length, there was a negative influence of the TS karyotype and of decreased androgen production/action. In conclusion, in DSD, both karyotype, especially with a 45,X cell line, and intrauterine androgenic production/action influence sex dimorphism of birth weight and length. It can be inferred that in children with normal karyotype and without a DSD, this dimorphism is mainly due to intrauterine androgenic production or action.

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