46,XX DSD and Antley-Bixler syndrome due to novel mutations in the cytochrome P450 oxidoreductase gene

Guaragna‐Filho, Guilherme; Castro, Carla Cristina Telles de Sousa; Carvalho, Rodrigo Ribeiro De; Coeli, Fernanda Borchers; Ferraz, Lúcio Fábio Caldas; Petroli, Reginaldo José; Mello, Maricilda Palandi de; Sewaybricker, Letícia Espósito; Lemos-Marini, Sofia Helena Valente de; D’Souza-Li, Lília; Miranda, Márcio Lopes; Maciel‐Guerra, Andréa Trevas; Guerra, Gil

doi:10.1590/s0004-27302012000800020

Cited by 16 publications

(16 citation statements)

References 27 publications

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“…The frequency of the salt-wasting form was also similar to that found in several population studies [13], confirming that it is the most relevant etiology of DSD due to both its high frequency and the high risk of death. Isolated clitoromegaly and syndromic features were also observed, which shows the importance of a wide range of clinical, hormonal, and molecular investigation for DSD, as well as the significance of the finding of dysmorphisms and associated malformations in cases of genital ambiguity [10, 14, 15]. …”

Section: Discussionmentioning

confidence: 99%

408 Cases of Genital Ambiguity Followed by Single Multidisciplinary Team during 23 Years: Etiologic Diagnosis and Sex of Rearing

Paula

Barros

Carpini

et al. 2016

International Journal of Endocrinology

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Objective. To evaluate diagnosis, age of referral, karyotype, and sex of rearing of cases with disorders of sex development (DSD) with ambiguous genitalia. Methods. Retrospective study during 23 years at outpatient clinic of a referral center. Results. There were 408 cases; 250 (61.3%) were 46,XY and 124 (30.4%) 46,XX and 34 (8.3%) had sex chromosomes abnormalities. 189 (46.3%) had 46,XY testicular DSD, 105 (25.7%) 46,XX ovarian DSD, 95 (23.3%) disorders of gonadal development (DGD), and 19 (4.7%) complex malformations. The main etiology of 46,XX ovarian DSD was salt-wasting 21-hydroxylase deficiency. In 46,XX and 46,XY groups, other malformations were observed. In the DGD group, 46,XY partial gonadal dysgenesis, mixed gonadal dysgenesis, and ovotesticular DSD were more frequent. Low birth weight was observed in 42 cases of idiopathic 46,XY testicular DSD. The average age at diagnosis was 31.7 months. The final sex of rearing was male in 238 cases and female in 170. Only 6.6% (27 cases) needed sex reassignment. Conclusions. In this large DSD sample with ambiguous genitalia, the 46,XY karyotype was the most frequent; in turn, congenital adrenal hyperplasia was the most frequent etiology. Malformations associated with DSD were common in all groups and low birth weight was associated with idiopathic 46,XY testicular DSD.

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Section: Discussionmentioning

confidence: 99%

408 Cases of Genital Ambiguity Followed by Single Multidisciplinary Team during 23 Years: Etiologic Diagnosis and Sex of Rearing

Paula

Barros

Carpini

et al. 2016

International Journal of Endocrinology

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“…Excessive gonadotropinmediated ovarian stimulation in hypogonadal women with 17OHD is a potential underlying mechanism leading to the development of ovarian cysts. In these cases, the development of ovarian cysts was avoided through dexamethasone, E, and P therapies (37), or, in one case, by the use of GnRH analogues. It is worth mentioning that all patients had reduced uterine volume at diagnosis.…”

Section: Fertility In 17ohdmentioning

confidence: 99%

Classic congenital adrenal hyperplasia and its impact on reproduction

Gomes

Bachega

Mendonca

2019

Fertility and Sterility

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Women with classic congenital adrenal hyperplasia (CAH) can suffer from impaired fertility rates as a result of increased androgen secretion or impaired sex steroid production. In virilizing CAH forms, such as 21-hydroxylase and 11b-hydroxylase deficiency, the low reported pregnancy rate is mainly secondary to a diminished desire to conceive. Optimal glucocorticoid and/or mineralocorticoid replacement, sufficient to normalize androgen and P levels in the follicular phase, allows natural conception in most cases. The remaining CAH forms exemplified by StAR, P450scc, P450-oxidoreductase, and 17a-hydroxylase/17-20 lyase deficiencies are associated with impaired sex steroid production. Several factors are involved in the true low fertility rate in this group: folliculogenesis arrest, uterine hypoplasia, and inadequate endometrial thickness related to aberrant androgen, estrogen, and P secretion. There are several reports of successful term pregnancies achieved through controlled ovarian hyperstimulation, followed by estrogen replacement and IVF. Progress in female genitalia reconstructive surgery, individualized hormonal therapies, psychosexual evaluation, and assisted reproductive technology have improved fertility and pregnancy outcomes in women with classic CAH. Finally, successful gestational management in CAH patients requires the close coordination of care between endocrinologists and obstetricians.

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“…The degree of external genitalia virilization is moderate in most 46,XX PORD patients, which is differently than the 21-hydroxylase deficiency. However, 46,XX cases presenting with severe virilization (Prader scores IV and V) including wrong sex assignment have also been described (7,14).…”

Section: Discussionmentioning

confidence: 99%

“…We described the second PORD case in our population (14), and provided a warning of this diagnostic possibility in patients with genital ambiguity and low serum androgen levels. We stressed the importance of continuous monitoring for glucocorticoid deficiency, the need for hormone replacement therapy with sex steroids at puberty and the benefit of the late surgical approach in facial hypoplasia.…”

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confidence: 95%

Long-term follow-up of a female with congenital adrenal hyperplasia due to P450-oxidoreductase deficiency

Bonamichi

Santiago

Bertola

et al. 2016

Arch. Endocrinol. Metab.

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SUMMARYP450 oxidoreductase deficiency (PORD) is a variant of congenital adrenal hyperplasia that is caused by POR gene mutations. The POR gene encodes a flavor protein that transfers electrons from nicotinamide adenine dinucleotide phosphate (NADPH) to all microsomal cytochrome P450 type II (including 21-hydroxylase, 17α-hydroxylase 17,20 lyase and aromatase), which is fundamental for their enzymatic activity. POR mutations cause variable impairments in steroidogenic enzyme activities that result in wide phenotypic variability ranging from 46,XX or 46,XY disorders of sexual differentiation, glucocorticoid deficiency, with or without skeletal malformations similar to Antley-Bixler syndrome to asymptomatic newborns diagnosed during neonatal screening test. Little is known about the PORD long-term evolution. We described a 46,XX patient with mild atypical genitalia associated with severe bone malformation, who was diagnosed after 13 years due to sexual infantilism. She developed large ovarian cysts and late onset adrenal insufficiency during follow-up, both of each regressed after hormone replacement therapies. We also described a late surgical approach for the correction of facial hypoplasia in a POR patient. Arch Endocrinol Metab. 2016;60(5):500-4

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46,XX DSD and Antley-Bixler syndrome due to novel mutations in the cytochrome P450 oxidoreductase gene

Cited by 16 publications

References 27 publications

408 Cases of Genital Ambiguity Followed by Single Multidisciplinary Team during 23 Years: Etiologic Diagnosis and Sex of Rearing

408 Cases of Genital Ambiguity Followed by Single Multidisciplinary Team during 23 Years: Etiologic Diagnosis and Sex of Rearing

Classic congenital adrenal hyperplasia and its impact on reproduction

Long-term follow-up of a female with congenital adrenal hyperplasia due to P450-oxidoreductase deficiency

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