Genital Ambiguity Research Articles

Prenatal Diagnosis of Partial Androgen Insensitivity Syndrome by Means of a 4-D Ultrasound Technique

J Obstet Gynaecol Can 2012;34(1):9 A 27-year-old primigravid woman was referred to our institution at 26 weeks’ gestation with suspected fetal ambiguous genitalia. Detailed real-time grey-scale and 4-D ultrasound examination of the fetal genitalia showed a micropenis with one testicle located in the relatively small scrotum (Figure 1; arrow indicates testicle). A diagnosis of X-linked partial androgen insensitivity was proposed after ultrasound features were compiled and a pedigree analysis performed. The patient delivered a 3100 g baby by Caesarean section at 39 weeks’ gestation. Findings from the physical examination of the newborn were completely normal except for genital ambiguity. The phallic structure was 1 cm long and 0.5 cm wide, with a single urogenital opening at the base of the phallic shaft and bilateral palpable gonads in the bifid scrotum (Figure 2). Visualization of the fetal testicle in the scrotum by ultrasonography is important in the prenatal diagnosis of partial androgen insensitivity.1

Two novel CYP11B1 mutations in congenital adrenal hyperplasia due to steroid 11β hydroxylase deficiency in a Tunisian family

Steroid 11β hydroxylase deficiency (11β-OHD) (OMIM # 202010) is the second most common form of congenital adrenal hyperplasia (CAH), accounting for 5–8% of all cases. It is an autosomal recessive enzyme defect impairing the biosynthesis of cortisol. The CYP11B1 gene encoding this enzyme is located on chromosome 8q22, approximately 40 kb from the highly homologous CYP11B2 gene encoding for the aldosterone synthase. Virilization and hypertension are the main clinical characteristics of this disease. In Tunisia, the incidence of 11β-OHD appears higher due to a high rate of consanguinity (17.5% of congenital adrenal hyperplasia). The identical presentation of genital ambiguity (females) and pseudo-precocious puberty (males) can lead to misdiagnosis with 21 hydroxylase deficiency. The clinical hallmark of 11β hydroxylase deficiency is variable, and biochemical identification of elevated precursor metabolites is not usually available. In order to clarify the underlying mechanism causing 11β-OHD, we performed the molecular genetic analysis of the CYP11B1 gene in a female patient diagnosed as classical 11β-OHD. The nucleotide sequence of the patient’s CYP11B1 revealed two novel mutations in exon 4: a missense mutation that converts codon AGT (serine) to ATT (isoleucine) (c.650G>T; p.S217I) combined with an insertion of a thymine at the c.652–653 position (c.652_653insT). This insertion leads to a reading frame shift, multiple incorrect codons, and a premature stop in codon 258, that drastically affects normal protein function leading to a severe phenotype with ambiguous genitalia of congenital adrenal hyperplasia due to 11β hydroxylase deficiency.

Congenital Adrenal Hyperplasia: 20-Year Experience in Southern Thailand

Background: Congenital adrenal hyperplasia (CAH) is a group of inherited disorders resulting deficiency of enzymes in the synthesis of cortisol. The clinical symptoms vary depending upon the specific enzymatic deficiency. Aim: To depict the clinical features, and laboratory and hormonal studies of CAH patients. Subjects and method: The medical records of pediatric patients diagnosed with CAH at Songklanagarind Hospital during 1991-2010 were reviewed. Results: There were 61 CAH patients. The most common type was 21-hydroxylase deficiency, salt-wasting type (21-OH, SW) (57.4%), followed by 21-hydroxylase deficiency, simple virilizing type (21-OH, SV) (31.1%). All patients with 20, 22-desmolase deficiency (n=4), 21-OH, SW (n=35) and 3β-hydroxysteroid dehydrogenase deficiency (n=3) presented with dehydration at the median age of 1.8 months. Genital ambiguity was found in 53% of girls with 21-OH, SW. Nineteen patients with 21-OH, SV presented with enlarged clitoris/penis at the median age of 5 years. The median cortisol level after ACTH stimulation was < 18 ug/dL in all types, except 19 patients with 21-OH, SV, in which the median cortisol was 19.49µg/dL. The basal 17-OHP level of these 19 patients was markedly elevated (5,985 ng/dL). All patients, except one, were assigned correctly as a boy or girl at the initial presentation. Conclusions: The most common type of CAH in our institute was 21-hydroxylase deficiency. The most common clinical manifestation in the newborn period is dehydration, and in the childhood period is the enlarged clitoris/penis. The most useful investigation for definite diagnosis of 21-hydroxylase deficiency is basal 17-OHP level.

Chromosomal and molecular abnormalities in a group of Brazilian infertile men with severe oligozoospermia or non-obstructive azoospermia attending an infertility service

To determine the frequency of genetic alterations in a population of Brazilian infertile men with severe oligozoospermia or non-obstructive azoospermia. Retrospective study of a group of 143 infertile men with severe oligozoospermia or non-obstructive azoospermia from the Andrology Outpatient Clinic of the Human Reproduction Service at the ABC School of Medicine. Of these patients, 100 had severe oligozoospermia, and 43 non-obstructive azoospermia. All patients underwent a genetic study which included karyotype analysis and Y-microdeletion investigation. Genetic abnormalities were found in 18.8% of the studied patients. Chromosomal abnormalities were found in 6.2% of the patients, being more prevalent in the azoospermia group (11.6%) than in the oligozoospermia group (4%). Chromosomal variants were found in 8.3%, and Y-chromosome microdeletions in 4.2% of patients. The high frequency of genetic alterations (18.8%) in our series justified performing a genetic investigation in a population with idiopathic infertility, as results may help determine the prognosis, as well as the choice of an assisted reproduction technique. Moreover, a genetic investigation could minimize the risk of transmitting genetic abnormalities to future generations such as genetic male infertility, mental retardation, genital ambiguity and/or birth defects.

Searching for harmony: parents’ narratives about their child’s genital ambiguity and reconstructive genital surgeries in childhood

This paper is a report of a narrative study of parents' experiences of their child's genital ambiguity and the place reconstructive surgeries have in their lives. Increasingly, the use of early reconstructive genital surgery has come under criticism. Few studies have explored parents' inclusion in the surgical decision-making process, their experiences of their child's surgeries or of parenting a child born with ambiguous genitalia. Narrative interviews about parents' experiences of having and caring for a child of uncertain gender and their rationale for reconstructive surgeries were conducted with 15 parents between October 2004 and February 2006. Interviews were recorded, transcribed verbatim and analysed in a narrative analysis framework. Narrative analysis resulted in three increasingly contextual and conceptual levels of stories. Connections between stories gave the basis for the synthesis of the data; interpretation identified three elements of shock, protection and anxiety, which influenced the parents. The parents identified the need for early and ongoing support from healthcare professionals. The parents expected professionals to be knowledgeable about the dilemmas surround disorders of sex development and have experience in managing care for themselves and their child. For the parents seeking a sense of harmony between their child's genital ambiguity and gender during childhood was important. Searching for this harmony became a dynamic and evolving process, which was built on their knowledge and increasing willingness to engage with professionals, negotiate their social worlds, emotional responses and belief systems.

557 LONG-TERM EVALUATION OF FEMINIZING GENITOPLASTY IN PATIENTS WITH VIRILIZING CONGENITAL ADRENAL HYPERPLASIA

You have accessJournal of UrologyPediatrics: Congenital Anomalies - Lower Urinary Tract & Genitalia1 Apr 2011557 LONG-TERM EVALUATION OF FEMINIZING GENITOPLASTY IN PATIENTS WITH VIRILIZING CONGENITAL ADRENAL HYPERPLASIA Maria Helena Sircili, Tania Aparecida Bachega, Madureira Guiomar, Marlene Inacio, Frederico Arnaldo Queiroz e Silva, Francisco Tibor Denes, and Berenice Bilharinho Mendonca Maria Helena SirciliMaria Helena Sircili São Paulo, Brazil More articles by this author , Tania Aparecida BachegaTania Aparecida Bachega São Paulo, Brazil More articles by this author , Madureira GuiomarMadureira Guiomar São Paulo, Brazil More articles by this author , Marlene InacioMarlene Inacio São Paulo, Brazil More articles by this author , Frederico Arnaldo Queiroz e SilvaFrederico Arnaldo Queiroz e Silva São Paulo, Brazil More articles by this author , Francisco Tibor DenesFrancisco Tibor Denes São Paulo, Brazil More articles by this author , and Berenice Bilharinho MendoncaBerenice Bilharinho Mendonca São Paulo, Brazil More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1282AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We found recent reports showing unsatisfactory results of feminizing genitoplasty. Our aim is to report the long-term evaluation of feminizing genitoplasty in 42 patients followed at a single public tertiary center with virilizing congenital adrenal hyperplasia, concerning also self-satisfaction and quality of sexual life. METHODS Genital ambiguity was classified according to Prader stage: 6 patients presented Prader II, 18 Prader III, 16 Prader IV and two Prader V. The clitoris length, ranged from 1.9 and 5.0 cm; 35 patients had one orifice and 7 had double perineal orifice.The surgical procedure and was done before 2 years of age in 19 patients. Urogenital sinus opening, was performed by two procedures: “Y-V”perineal flap in 34 patients and cut-back incision in 8 patients. The follow up ranged from 3 to 24 years. RESULTS Cosmetic and functional results were considered good in 70%, surgical complications occurred in 20.5% of the patients. Dilations with acrylic molds, in the post pubertal period, were necessary in 3 of them with good results. Sexual activity was present in 52% of these patients and all of them refer genital sensibility with orgasm during sexual intercourse. CONCLUSIONS We conclude that single-stage feminizing genitoplasty consisting of vulvoplasty, clitoroplasty, and Y-V perineal flap produced good cosmetic and functional results in virilized girls with CAH, with good self-satisfaction and adequate sexual life. Also this surgical approach prevented the need for neovaginaplasty even in patients with high vaginal insertion. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e225 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Maria Helena Sircili São Paulo, Brazil More articles by this author Tania Aparecida Bachega São Paulo, Brazil More articles by this author Madureira Guiomar São Paulo, Brazil More articles by this author Marlene Inacio São Paulo, Brazil More articles by this author Frederico Arnaldo Queiroz e Silva São Paulo, Brazil More articles by this author Francisco Tibor Denes São Paulo, Brazil More articles by this author Berenice Bilharinho Mendonca São Paulo, Brazil More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Long-term Follow-up after Feminizing Genital Reconstruction in Patients with Ambiguous Genitalia and High Vaginal Confluence

We evaluated the long-term results of feminizing genital reconstruction in patients with genital ambiguity with high vaginal confluence. The medical records of 10 consecutive patients with ambiguous genitalia and high vaginal confluence who underwent feminizing genital reconstruction from 1996 to 2007 were reviewed. Seven patients had congenital adrenal hyperplasia, one had mixed gonadal dysgenesis, one had partial androgen insensitivity, and one had 5-alpha reductase deficiency syndrome. Median age at operation was 21 months (range, 2-47 months). Median follow up was 7.7 yr. Of the six patients who underwent feminizing genital reconstruction with the Gonzalez method, three had good results. Of the other three patients, one had a urethrovaginal fistula and underwent fistula repair 9 yr after, one had distal vaginal stenosis and underwent revision vaginoplasty 9 yr after, and one had a urethrovaginal fistula and urethral stricture. The patient with urogenital mobilization had persistent urogenital sinus. Feminizing genitoplasty using the Gonzalez method showed good long-term results in patients with ambiguous genitalia and Congenital adrenal hyperplasia. The procedure is less invasive than other approaches and results in excellent cosmetic outcomes; and complications can be corrected by relatively simple procedures.

Transforming Sexuality: The Medical Sources of Karl Heinrich Ulrichs (1825-95) and the Origins of the Theory of Bisexuality

This article explores the medical references in the writings of the German jurist and activist Karl Heinrich Ulrichs as a means of breaking new ground in diverse fields (including history of medicine, history of sexuality, and gender history). It demonstrates that the theory of bisexuality has a much deeper and more textured genealogy than has been hitherto appreciated and that dual-gendered bodies and minds must be better recognized as important through the nineteenth century. Specifically, it demonstrates that classifications and rhetoric of hermaphroditism, and other dual-gendered categories (e.g., sexual dualism and anatomical bisexuality), were deployed in diverse contexts through the period, often with little or no reference to the occurrence of genital ambiguities. Important discourses in embryology, utilized by Ulrichs, suggested that all individuals, in the earliest stages of fetal development, were hermaphroditic. In making an analogy among the ontogeny of sex anatomy, hermaphroditism, and the development of erotic preferences, Ulrichs sought to naturalize homoeroticism, rendering social and legal prohibitions untenable. His advocacy, however, was counterbalanced by the Prussian forensic expert Johann Ludwig Casper who had made some conceptual maneuvers similar to Ulrichs only couched in the rhetoric of pathology. Ulrichs was equivocal in his use of forensic works such as Casper's, condemning their authors but recognizing similarities with his own gender schema.

Approach to Assigning Gender in 46,XX Congenital Adrenal Hyperplasia with Male External Genitalia: Replacing Dogmatism with Pragmatism

The goal of sex assignment is to facilitate the best possible quality of life for the patient. Factors such as reproductive system development, sexual identity, sexual function, and fertility are important considerations in this regard. Although some DSD gender assignments are relatively straightforward, those with midstage genital ambiguity and unclear gonadal function represent a major challenge. A recent major change in DSD care has been to encourage a male assignment for 46,XY infants with ambiguous genitalia who have evidence of testicular function and in utero central nervous system androgen exposure. In contrast, assignment of virilized 46,XX DSD patients remains female when ovaries and internal organs are present, regardless of the extent of virilization of the external genitalia. In this paper, we propose consideration of male assignment for these 46,XX patients who have fully developed male genitalia based on available outcome data.

Long-Term Surgical Outcome of Masculinizing Genitoplasty in Large Cohort of Patients With Disorders of Sex Development

We evaluated the results of masculinizing genitoplasty in a large cohort of patients with disorders of sex development treated at a single public tertiary center. We evaluated 52 patients with 46,XY and 7 with 46,XX disorders of sex development with proximal hypospadias and genital ambiguity reared as males who had undergone surgery between 1965 and 2008. Mean +/- SD followup was 14.1 +/- 9.2 years and median age at last examination was 22 years, with 38 patients having reached adulthood. Morphological result and urinary stream were evaluated by a physician. Urinary and sexual symptoms, and satisfaction with surgical results were assessed by questionnaire. Mean penile length at diagnosis was compared between 46,XY patients and showed that those with 5alpha-reductase 2 deficiency had the shortest penile length (-5.4 +/- 1.2 SD). At the last clinical evaluation following surgical and hormonal treatment mean +/- SD penile length in 38 adults was 7.5 +/- 2.1 cm (range 4 to 12), corresponding to -4.3 +/- 1.3 SD (-6.5 to -1.5). All but 2 patients had penile length less than -2 SD. At that time mean penile length remained shorter in patients with 5alpha-reductase 2 deficiency (-5.4 +/- 1 SD) compared to those with testosterone production deficiency or indeterminate disorders of sex development (p <0.05). There was no statistical difference between mean penile length before and after treatment in all etiological groups (p >0.05). Morphological results were good in 43% of patients, fair in 54% and poor in 3%. The most common complications were urethral fistula (51%) and urethral stenosis (22%). Dribbling after voiding was the most frequent urinary symptom. Satisfaction with surgical results was reported by 89% of patients. Among adults 87% were sexually active, with 64% reporting normal sexual activity. Most patients with 46,XY disorders of sex development were satisfied with long-term results of masculinizing genitoplasty, although specific complaints about small penile length, sexual activity and urinary symptoms were frequent. New surgical approaches should be developed to ensure full satisfaction in adulthood among patients with disorders of sex development.

Congenital adrenal hyperplasia due to 21‐hydroxylase deficiency

21-Hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia (CAH), an inherited disorder of steroidogenesis. In its severe form, CAH causes genital ambiguity in females. Molecular genetic analysis of fetal DNA obtained by amniocentesis or chorionic villus sampling is used to diagnose steroid 21-OHD deficiency in utero. Large ongoing studies show that appropriate prenatal treatment of pregnant mothers with dexamethasone is effective and safe for both the fetus and the mother. It reduces ambiguous genitalia in the female affected fetus and thus avoids unnecessary genitoplasty in the newborn female.

Long-Term Surgical Outcome of Masculinizing Genitoplasty in a Large Cohort of Patients With Disorders of Sex Development (DSD)

Purpose To evaluate the results of masculinizing genitoplasty in a large cohort of DSD patients treated at a single public tertiary center. Material and Methods We evaluated 65 patients (57 with 46,XY DSD and 8 with 46,XX DSD reared as males) with proximal Hypospadias and genital ambiguity that were submitted to surgery from 1965 to 2008. The mean follow-up was 15.1±10 years and the average age at the last examination was 25.9±14.1 years. Cosmetic result and urinary stream were objectively evaluated and questionnaires were applied inquiring about urinary and sexual symptoms and self-satisfaction with surgical results. Results Cosmetic results were good in 44%, regular in 53% and poor in 3% of the cases. Mean penile length at last clinical evaluation in postpubertal patients was 7.8 ±2.4 cm (-6.5 to -1.5 SDS). Mean penile length at diagnosis was smaller in the 5αRD2 deficiency group compared to undetermined 46,XY DSD group (p Conclusions Although 85% of the patients were satisfied, specific complaints about penis size, sexual activity or urinary symptoms were frequent. New approaches should be developed to achieve full satisfaction of DSD patients in adulthood.

Congenital Adrenal Hyperplasia and Concurrent Turner Syndrome Mosaicism

Background: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder characterized by impaired cortisol synthesis, virilization, and in the case of severe enzyme deficiency, insufficient production of aldosterone resulting in salt wasting and life-threatening adrenal crisis. In the severe salt-wasting classic form, the disorder can result in genital ambiguity, short stature, sexual precocity, irregular menses, and compromised fertility. Turner syndrome (TS) is a sex chromosomal defect which genetically implies 45,X karyotype.

Ambiguous genitalia in neonates: a 4-year prospective study in a localized area

This study aimed to determine the possible etiology ot ambiguous genitalia in 41 newborn intants at a referral hospital in Hofuf city, Saudi Arabia. In 46,XX karyotype patients (n 14), congenital adrenal hyperplasia and general malformation disorder were the most common causes of genital ambiguity, while in 46,XY karyotype patients (n=18), testosterone pathway biosynthetic defect was the most common cause even in conjunction with a generalized malformation disorder. In patients with abnormal karyotype (n=3), 1 had trisomy 18 (47,XX) and died after 3 months and 2 had different types of mosaic Turner syndrome. The karyotype was undetermined in 6 natients. Positive family history of ambiguous genitalia was noted in 4 patients.

Primary Caregivers of Children Affected by Disorders of Sex Development: Mental Health and Caregiver Characteristics in the Context of Genital Ambiguity and Genitoplasty

Purpose. To determine the relationship between having a child with a DSD including ambiguous external genitalia, as well as the decision of whether or not to have early genitoplasty for that child, on the mental health and parenting characteristics of caregivers. Materials and Methods. Caregivers were recruited from centers that specialize in DSD medicine and completed the Beck Depression Inventory 2nd Edition (BDI-2), Beck Anxiety Index (BAI), Parent Protection Scale (PPS), Child Vulnerability Scale (CVS) and Parenting Stress Index/Short Form (PSI/SF). Results and Conclusions. Sixty-eight caregivers provided informed consent and completed the study. Among female caregivers whose children never received genitoplasty, greater parenting stress was reported (F(1, 40) = 5.08, p = .03). For male caregivers, those whose children received genitoplasty within the first year of life reported more overprotective parenting and parenting stress than those whose children received genitoplasty later than 12 months of age (F(1, 13) = 6.16, p = 0.28); F(1, 15) = 6.70, p = .021), respectively).

Primary Caregivers of Children Affected by Disorders of Sex Development: Mental Health and Caregiver Characteristics in the Context of Genital Ambiguity and Genitoplasty

Primary Caregivers of Children Affected by Disorders of Sex Development: Mental Health and Caregiver Characteristics in the Context of Genital Ambiguity and Genitoplasty

Variants of Gender Differentiation in Somatic Disorders of Sex Development: Recommendations for Version 7 of the World Professional Association for Transgender Health's Standards of Care

ABSTRACT Many individuals born with genital ambiguity and related conditions (recently recategorized as disorders of sex development [DSD]) experience gender uncertainty or gender dysphoria, and some may undergo self-initiated gender change. Whether these phenomena are sufficiently similar to the presentations of gender identity variants (GIVs) in non-DSD persons (gender identity disorder [GID] in current psychiatric terminology) to warrant the application of identical diagnostic criteria and treatment approaches is under debate. This review takes the position that the differences in phenomena, context of presentation, etiology, and treatment settings are so large that identical diagnoses and treatment approaches are not justified and may be detrimental to the individuals in need of care, although more systematic comparisons are needed for definitive conclusions. On the other hand, there is increasing overlap of DSD and non-DSD individuals with gender problems in professional care personnel, assessment methods, aspects of medical and psychosocial management, and support groups and gender activism. Thus, a comprehensive revision of the Standards of Care (SOC) needs to include pertinent material on DSD, and clinicians caring for individuals with GIV should be acquainted with the key clinical issues in both. The remainder of this article summarizes the limited information available for DSD on the issues addressed in the sixth edition of the SOC for non-DSD GIV.

Clinical, Genetic, and Enzymatic Characterization of P450 Oxidoreductase Deficiency in Four Patients

P450 oxidoreductase (POR) deficiency causes disordered steroidogenesis; severe mutations cause genital ambiguity in both sexes plus the Antley-Bixler skeletal malformation syndrome, whereas mild mutations can cause adult infertility. We describe four patients with POR deficiency and identify and characterize the activities of their mutations. A 46,XY male with micropenis and two 46,XX female infants with genital ambiguity presented with skeletal malformations, and a 46,XX adolescent presented with primary amenorrhea, elevated 17alpha-hydroxyprogesterone, and low sex steroids. The coding regions of the POR gene were sequenced, and the identified mutations were recreated in human POR cDNA expression vectors lacking 27 N-terminal residues. POR and human P450c17 were expressed in bacteria. POR activity was measured by four assays: reduction of cytochrome c, oxidation of reduced nicotinamide adenine dinucleotide phosphate, and support of the 17alpha-hydroxylase and 17,20 lyase activities of P450c17. All four patients were compound heterozygotes for POR mutations, including five novel mutations: L577R, N185K, delE217, and frameshift mutations 1363delC and 697-698insGAAC. N185K and delE217 lacked measurable activity in the assays based on P450c17 but retained partial activity in the assays based on cytochrome c. As assessed by V(max)/Km, L577R supported 46% of 17alpha-hydroxylase activity but only 27% of 17,20 lyase activity. Computational modeling of these novel mutants revealed the structural basis for their reduced or absent activities. These patients illustrate the broad clinical spectrum of POR deficiency, including amenorrhea and infertility as the sole manifestation. POR assays based on P450c17 correlate well with hormonal and clinical phenotypes.

Novel Mutations inCYP11B1Gene Leading to 11β-Hydroxylase Deficiency in Brazilian Patients

Deficiency of 11 beta-hydroxylase results in the impairment of the last step of cortisol synthesis. In females, the phenotype of this disorder includes different degrees of genital ambiguity and arterial hypertension. Mutations in the CYP11B1 gene are responsible for this disease.The objective of the study was to screen the CYP11B1 gene for mutations in two unrelated Brazilian females with congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency.The coding and intron-exon junction regions of CYP11B1 were totally sequenced. A putative splice mutation was further investigated by minigene transcription.We report two novel CYP11B1 mutations in these Brazilian patients. An Arabian Lebanese descendent female was found to be homozygous for a cytosine insertion at the beginning of exon 8, changing the 404 arginine to proline. It alters the open reading frame, creating a putative truncated protein at 421 residue, which eliminates the domain necessary for the association of heme prosthetic group. A severely virilized female was homozygous for the g.2791G>A transition in the last position of exon 4. This nucleotide is also part of 5' intron 4 donor splice site consensus sequence. Minigene experiments demonstrated that g.2791G>A activated an alternative splice site within exon 4, leading to a 45-bp deletion in the transcript. The putative translation of such modified mRNA indicates a truncated protein at residue 280.We describe two novel mutations, g.4671_4672insC and g.2791G>A, that drastically affects normal protein structure. These mutations abolish normal enzyme activity, leading to a severe phenotype of congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency.

Congenital Adrenal Hyperplasia: A Critical Appraisal of the Evolution of Feminizing Genitoplasty and the Controversies Surrounding Gender Reassignment

Although congenital adrenal hyperplasia (CAH) is the most common cause of genital ambiguity, its surgical treatment remains controversial and often times difficult, especially in cases of high urethro-vaginal confluence. Many aspects are still uncertain, such as the timing of feminizing genitoplasty and type of surgical technique. The objective of this study is to provide a thorough review of the surgical management of children with CAH, discussing the evolution of feminizing genitoplasty and its different techniques, and also to critically appraise the available literature on the timing of surgical intervention and gender reassignment. Prospective long-term studies evaluating the results of modern feminizing genitoplasty techniques are needed as current evidence is based on outdated operations that are no longer used. To date, there have been no studies comparing early and delayed feminizing genitoplasty with regard to psychological outcomes. All families should be counseled regarding the controversies and treatment options, including the watchful waiting approach.