A clinical algorithm to diagnose differences of sex development

León, Nayla Y; Reyes, Alejandra P; Harley, Vincent R.

doi:10.1016/s2213-8587(18)30339-5

Cited by 41 publications

(30 citation statements)

References 125 publications

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“…However, there is no uniform consensus regarding the assignment and surgery. [2] In Africa, due to cultural factors, most 46,XX OT-DSDs are reared as males; however, in countries beyond Africa, these individuals tend to be reared as females. [12] Ideally, a multidisciplinary team consisting of specialists in urology, gynecology, endocrinology, psychology, psychiatry, radiology, pathology, genetics, and clinical biochemistry should be mandatory for the assessment and care of such patients.…”

Section: Discussionmentioning

confidence: 99%

“… [12] Ideally, a multidisciplinary team consisting of specialists in urology, gynecology, endocrinology, psychology, psychiatry, radiology, pathology, genetics, and clinical biochemistry should be mandatory for the assessment and care of such patients. [2] Most importantly, the functional potential of the internal and external genitalia should be determined, [14] as fertility is often impaired in cases of OT-DSD for both males and females. Although females can be fertile, that is, if the internal genitalia are appropriate, [14] an intact Y chromosome is required for spermatogenesis.…”

Section: Discussionmentioning

confidence: 99%

“… [1] Disorders of sex development (DSDs) are classified into 3 categories, namely, sex chromosome DSD, 46,XY DSD, and 46,XX DSD. [2] Ovotesticular DSD (OT-DSD), previously known as true hermaphroditism, describes individuals who have both testicular and ovarian tissues, with an overall incidence of 1 out of 100,000 live births. [3] …”

Section: Introductionmentioning

confidence: 99%

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46, XX Ovotesticular disorder of sex development (true hermaphroditism) with seminoma

Liu²,

Peng³

et al. 2020

Medicine

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Rationale: Ovotesticular disorder of sex development (DSD), previously known as true hermaphroditism, is a disorder in which individuals have both testicular and ovarian tissues. Instances of tumors arising in the gonads of individuals with 46,XX ovotesticular DSD are uncommon. Patient concerns: We report a case of a 36-year-old phenotypical male with a chief complaint of an abdominal mass for 3 months. He reported normal erections and regular menses. Computerized tomography showed a large tumor measuring 15 × 10 cm in size, a uterus, and a cystic ovary. Diagnosis: 46, XX ovotesticular DSD with seminoma. Interventions: The patient was treated with neochemotherapy (etoposide and cisplatin), surgery, chemotherapy, and testosterone replacement. Outcomes: At the 13-month follow-up, the patient reported satisfactory erections, and no evidence of disease was found. Conclusion: Cases of 46,XX ovotesticular DSD with seminoma are uncommon. Our case reveals the importance of surgery combined with neochemotherapy, chemotherapy, and testosterone replacement in these patients to improve the prognosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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46, XX Ovotesticular disorder of sex development (true hermaphroditism) with seminoma

Liu²,

Peng³

et al. 2020

Medicine

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“…Hence, it has been suggested that direct analysis of the SRD5A2 gene without assessing the T:DHT ratio may be an alternative approach in children suspected to have 5-ARD [Chan et al, 2013]. Greater availability of advanced molecular techniques such as NGS may further change the diagnostic algorithms [León et al, 2019]. In India, the cost of serum DHT assay is around € 24.00, cost of sequencing of all 5 exons of SRD5A2 gene is around € 40.00, and of screening for the hotspot pathogenic variant is around € 8.00.…”

Section: Discussionmentioning

confidence: 99%

Spectrum of Pathogenic Variants in SRD5A2 in Indian Children with 46,XY Disorders of Sex Development and Clinically Suspected Steroid 5α-Reductase 2 Deficiency

Kumar

Sharma

Faruq

et al. 2019

Sex Dev

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The aim of this study was to assess the prevalence of pathogenic variants in the SRD5A2 gene in children with 46,XY disorders of sex development (DSD) with normal to high serum testosterone levels and absence of Müllerian structures on imaging and to evaluate the genotype-phenotype correlation. Seventy-five patients with 46,XY DSD and probable clinical diagnosis of 5α-reductase 2 deficiency or androgen insensitivity syndrome were enrolled. Genetic analysis was done for pathogenic variants in SRD5A2, and the genotype-phenotype correlation was studied. As a result, 10 pathogenic or likely pathogenic biallelic variants in SRD5A2, either homozygous or compound heterozygous, were identified in 25 of 75 (33.3%) patients. The hCG stimulated testosterone: dihydrotestosterone (T:DHT) ratio was elevated in all patients with pathogenic variants in SRD5A2 and in nearly 90% of those without pathogenic variants in SRD5A2 in whom this was assessed. The missense pathogenic variant p.R246Q was a hotspot. One novel pathogenic variant p.Y178*, and a variant p.F194I, not previously reported in patients with 5α-reductase 2 deficiency, were identified. The missense variant p.F194I was predicted as deleterious and damaging by in silico analysis and as likely to reduce the enzyme activity by protein modeling. In conclusion, pathogenic variants in SRD5A2 can be detected in a wide spectrum of Indian patients with 46,XY DSD. Molecular genetic analysis should be considered as a first-line test as the T:DHT ratio lacks specificity and a hotspot variant is present in a vast majority.

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“…6,7 When the laparoscopy was required for our patient, it was considered to take a sample from the ovary in terms of the possibility of ovotestis. 13 Although a normal gonadal appearance was seen, this would not always indicate a normal histology as a demarcation line was not remarkable in some patients with ovotestis described in literature. 14 Unlikely to most of the patients with aromatase deficiency, the biopsy specimens from both gonads of the present case were histologically consistent with normal ovarian tissue, and no cystic structure developed during the follow-up.…”

Section: Discussionmentioning

confidence: 81%

A novel compound heterozygous variant in CYP19A1 resulting in aromatase deficiency with normal ovarian tissue

Acar¹,

Paketçi²,

Önay³

et al. 2020

Turk J Pediatr

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Background. Aromatase deficiency leading to virilization in mother and female fetuses during pregnancy is a rare disease. It is characterized by impaired estrogen production, increased gonadotropins, and ovarian cysts. Case. Herein, we report a clinical phenotype of the virilized female due to a novel compound heterozygous variant in CYP19A1 [IVS10 + 1 G> A; c.344 G> A (p.R115Q)], with normal gonadotropin levels at the time of admission and histologically normal ovarian tissues. Conclusion. Aromatase deficiency should also be considered even if the initial follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels are normal, and ovarian cysts are lacking.

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A clinical algorithm to diagnose differences of sex development

Cited by 41 publications

References 125 publications

46, XX Ovotesticular disorder of sex development (true hermaphroditism) with seminoma

46, XX Ovotesticular disorder of sex development (true hermaphroditism) with seminoma

Spectrum of Pathogenic Variants in <b><i>SRD5A2</i></b> in Indian Children with 46,XY Disorders of Sex Development and Clinically Suspected Steroid 5α-Reductase 2 Deficiency

A novel compound heterozygous variant in CYP19A1 resulting in aromatase deficiency with normal ovarian tissue

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