Intersex Research Articles

Excluding embryos with two novel mutations in FREM2 gene by the next-generation sequencing-based single nucleotide polymorphism haplotyping.

Fraser syndrome is a rare autosomal recessive malformation disorder. It is characterized by cryptophthalmos, syndactyly, urinary tract abnormalities and ambiguous genitalia. This condition is due to homozygous or heterozygous mutations in the FRAS1, FREM1, FREM2, and GRIP1 genes. In the present study, we recruited a Chinese family with Fraser syndrome. Two novel mutations c.7542_7543insG and c.2689C>T in the FREM2 gene were detected in this Fraser syndrome family by PCR-based sequencing. The next-generation sequencing-based single nucleotide polymorphism haplotyping method was applied to exclude these two mutations in 9 blastocysts obtained from the patient. After obtaining consent and informing the risk, the patient received in vitro fertilization and embryo transfer treatment with an embryo carrying a heterozygous mutation. Finally, she delivered a healthy baby without any complications on March 17, 2019. In conclusion, we first reported two novel mutations in the FREM2 gene associated with the risk of Fraser syndrome. Moreover, we described a next-generation sequencing-based single nucleotide polymorphism haplotyping method to select the ‘right’ embryos from patients with Fraser syndrome for in vitro fertilization and embryo transfer treatment.

Expanding the spectrum of syndromic PPP2R3C-related XY gonadal dysgenesis to XX gonadal dysgenesis.

Homozygous variants in PPP2R3C have been reported to cause a syndromic 46,XY complete gonadal dysgenesis phenotype with extragonadal manifestations (GDRM, MIM# 618419) in patients from four unrelated families, whereas heterozygous variants have been linked to reduced fertility with teratozoospermia (SPGF36, MIM# 618420) in male carriers. We present eight patients from four unrelated families of Turkish and Indian descent with three different germline homozygous PPP2R3C variants including a novel in-frame duplication (c.639_647dupTTTCTACTC, p.Ser216_Tyr218dup). All patients exhibit recognizable facial dysmorphisms allowing gestalt diagnosis. In two 46,XX patients with hypergonadotropic hypogonadism and nonvisualized gonads, primary amenorrhea along with absence of secondary sexual characteristics and/or unique facial gestalt led to the diagnosis. 46,XY affected individuals displayed a spectrum of external genital phenotypes from ambiguous genitalia to complete female. We expand the spectrum of syndromic PPP2R3C-related XY gonadal dysgenesis to both XY and XX gonadal dysgenesis. Our findings supported neither ocular nor muscular involvement as major criteria of the syndrome. We also did not encounter infertility problems in the carriers. Since both XX and XY individuals were affected, we hypothesize that PPP2R3C is essential in the early signaling cascades controlling sex determination in humans.

Ethical aspects of gender assignment in ambiguous genitalia - congenital adrenal hyperplasia: a case report

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder commonly caused by mutation of the CYP21A2 gene, resulting in deficiency of an enzyme required for cortisol synthesis in the adrenal cortex. In 90-95% of cases, the deficient enzyme is 21-hydroxylase (21-OH), with an incidence ranging from 1 in 5,000 to 15,000 live births across various ethnic and racial backgrounds. In classical 21-OH deficiency (21-OHD) CAH, excessive androgen exposure in the fetus results in virilization at birth.1
 The management of ambiguous genitalia in children with CAH presents a unique and ethically challenging decision-making dilemma for the medical team. Insensitive and poorly informed statements made in the delivery room may cause long-term psychological problems for the families. It is important to refrain from assigning gender until sufficient diagnostic information can be gathered. Parents, as guardians, and the supporting medical team must make decisions on behalf of the child, with the goal of enabling the child to grow into a healthy and happy adult with his or her assigned gender.2,3 We report a case of a child with CAH, focusing on the ethical challenges in management of ambiguous genitalia.

The Spectrum of CYP21A2 Gene Mutations from 16 Families of Congenital Adrenal Hyperplasia: Genotype-Phenotype Correlation.

Aim:Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder of the adrenal steroidogenic pathway. The most common form of CAH is due to 21-hydroxylase deficiency resulting from mutations in CYP21A2 gene. The present study aimed to identify CYP21A2 common gene mutations, phenotype correlation, and to analyze the segregation pattern in CAH patients, parents, and siblings.Materials and Methods:Sixteen families having at least one classic CAH child in each family, a total of 58 subjects were recruited. The presence of six most common gene mutations, namely, Intron 2 (c.293-13A/C>G), c.844G>T (p.Val282Leu), c.1019G>A (p.Arg340His), c.92C>T (p.Pro31Leu), c.955C>T (p.Gln319*), and c.518T>A (p.Ile173Asn) in CYP21A2 gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using specific primers.Results:Out of 16 classic CAH females analyzed, salt-wasting (SW) form was present in 12 (75%) and simple virilizing form in four (25%) children. Isolated clitoromegaly was the most common clinical presentation followed by ambiguous genitalia. The most common mutation observed in CAH patient population was Intron 2 (c.293-13A/C>G) (100%) followed by p.Pro31Leu (98%), p.Gln319* (93%), p.Val282Leu (91.4%), and p.Ile173Asn (19%). Although p.Arg340His mutation was not observed in this study. Interestingly, Intron 2 (c.293-13A/C>G) homozygous was observed in 31.3% of the entire study cohort and p.Ile173Asn mutation was found to be associated with SW form.Conclusions:Our results suggested a high prevalence of CYP21A2 gene mutations among CAH patients and heterogeneous mutation spectrum in their families of south Indian cohort. The outcomes afford valuable evidence for premarital and prenatal screening as well as planning suitable programs to prevent the development of CAH in Indian population.

Creation of Neovagina Using Complete Laparoscopic Dissection

Study Objective Exclusive laparoscopic dissection for creation of neovagina in MRKH Design Video with step-by-step description of technique Setting Department of Gynaecology at BLK Max Superspeciality Hospital, a tertiary care teaching hospital in Delhi, India Patients or Participants 27-year-old patient with MRKH syndrome, married for 6 months came for creation of neo-vagina Interventions Neovagina was created using complete laparoscopic dissection. Measurements and Main Results The surgery required lesser time than combined laparoscopic-perineal approach. The operation duration was 25 minutes. Blood loss was 20 ml. The vaginal lumen accommodated the vaginal mould well and patient could very comfortably change the vaginal mould herself from 4th day onwards. Conclusion For creation of neovagina, MacIndoe's method had been gold standard for many years. Combined laparoscopic and perineal technique with peritoneal pull through has become popular due to minimal morbidity. In this video, we show the technique of complete laparoscopic dissection right up to skin at vaginal dimple. As this dissection is completely under vision, it minimises the risk of damage to the bladder and rectum, which is not uncommon with perineal dissection. In addition, few medial fibers of levator ani can be divided under vision with this technique which avoids cicatrisation of vagina in future. Exclusive laparoscopic dissection for creation of neovagina in MRKH Video with step-by-step description of technique Department of Gynaecology at BLK Max Superspeciality Hospital, a tertiary care teaching hospital in Delhi, India 27-year-old patient with MRKH syndrome, married for 6 months came for creation of neo-vagina Neovagina was created using complete laparoscopic dissection. The surgery required lesser time than combined laparoscopic-perineal approach. The operation duration was 25 minutes. Blood loss was 20 ml. The vaginal lumen accommodated the vaginal mould well and patient could very comfortably change the vaginal mould herself from 4th day onwards. For creation of neovagina, MacIndoe's method had been gold standard for many years. Combined laparoscopic and perineal technique with peritoneal pull through has become popular due to minimal morbidity. In this video, we show the technique of complete laparoscopic dissection right up to skin at vaginal dimple. As this dissection is completely under vision, it minimises the risk of damage to the bladder and rectum, which is not uncommon with perineal dissection. In addition, few medial fibers of levator ani can be divided under vision with this technique which avoids cicatrisation of vagina in future.

Pubertal development in 46,XY patients with NR5A1 mutations

PurposeMutations in the NR5A1 gene, encoding the transcription factor Steroidogenic Factor-1, are associated with a highly variable genital phenotype in patients with 46,XY differences of sex development (DSD). Our objective was to analyse the pubertal development in 46,XY patients with NR5A1 mutations by the evaluation of longitudinal clinical and hormonal data at pubertal age.MethodsWe retrospectively studied a cohort of 10 46,XY patients with a verified NR5A1 mutation and describe clinical features including the external and internal genitalia, testicular volumes, Tanner stages and serum concentrations of LH, FSH, testosterone, AMH, and inhibin B during pubertal transition.ResultsPatients who first presented in early infancy due to ambiguous genitalia showed spontaneous virilization at pubertal age accompanied by a significant testosterone production despite the decreased gonadal volume. Patients with apparently female external genitalia at birth presented later in life at pubertal age either with signs of virilization and/or absence of female puberty. Testosterone levels were highly variable in this group. In all patients, gonadotropins were constantly in the upper reference range or elevated. Neither the extent of virilization at birth nor the presence of Müllerian structures reliably correlated with the degree of virilization during puberty.ConclusionPatients with NR5A1 mutations regardless of phenotype at birth may demonstrate considerable virilization at puberty. Therefore, it is important to consider sex assignment carefully and avoid irreversible procedures during infancy.

Chromosome 9p terminal deletion in nine Egyptian patients and narrowing of the critical region for trigonocephaly.

BackgroundThis study aimed to delineate the clinical phenotype of patients with 9p deletions, pinpoint the chromosomal breakpoints, and identify the critical region for trigonocephaly, which is a frequent finding in 9p terminal deletion.MethodsWe investigated a cohort of nine patients with chromosome 9p terminal deletions who all displayed developmental delay, intellectual disability, hypotonia, and dysmorphic features. Of them, eight had trigonocephaly, seven had brain anomalies, seven had autistic manifestations, seven had fair hair, and six had a congenital heart defect (CHD).ResultsKaryotyping revealed 9p terminal deletion in all patients, and patients 8 and 9 had additional duplication of other chromosomal segments. We used six bacterial artificial chromosome (BAC) clones that could identify the breakpoints at 17–20 Mb from the 9p terminus. Array CGH identified the precise extent of the deletion in six patients; the deleted regions ranged from 16 to 18.8 Mb in four patients, patient 8 had an 11.58 Mb deletion and patient 9 had a 2.3 Mb deletion.ConclusionThe gene deletion in the 9p24 region was insufficient to cause ambiguous genitalia because six of the nine patients had normal genitalia. We suggest that the critical region for trigonocephaly lies between 11,575 and 11,587 Mb from the chromosome 9p terminus. To the best of our knowledge, this is the minimal critical region reported for trigonocephaly in 9p deletion syndrome, and it warrants further delineation.

Особливості фемінізуючої хірургічної корекції в дітей з розладами статевого розвитку

Purpose – to analyze own results of surgical treatment of serious forms of disorders of sexual development (DSD) in children after feminizing surgeries. To define practical protocol guides on the choice of the type of surgical correction. Materials and methods. Over the past 5 years surgeons of Lviv regional paediatric clinical hospital «OHMATDYT» have examined 12 children with DSD, signs of hermaphroditism (intersex). After complex examination the following states were diagnosed: androgenital syndrome in 5 girls (referred for further treatment to Kyiv paediatric medical centres); true hermaphroditism – 1 child; mixed gonadal dysgenesis (MCG) – 3 children; female pseudohermaphroditism (without determining genesis) – 1 child; partial testicular feminization syndrome, Morris syndrome (male pseudohermaphroditism) – 2 children. In connection with marked masculinization of external genitalia two children with MCG and the girl with pseudohermaphroditism underwent feminizing surgery, namely genital zone reconstruction, mobilization and excision of urogenital sinus walls, excision of genital cavernous bodies (in children with MCG) with clitoroplasty, vulvoplasty with labioplasty and vaginoplasty. Children with Morris syndrome are being prepared to feminizing surgery. Results. Each child had a personal examination plan. Verification of a child’s state lasted from several weeks to 2–3 months. Children who underwent feminizing surgery did not have male structures and had relatively well-developed female structures. More «natural», less traumatizing correction was preformed for each specific case. In all children who underwent surgery vagina opened into urogenital sinus lower than external urethral sphincter, so there was no need to form front vagina wall (back and side walls were formed). Out of all children treated in our hospital gender was legally changed to the opposite. Conclusions. The birth of a child with DSD is a most challenging problem for parents, doctors, psychologists and social workers. Such states require complex examination. Children with severe hypospadias must undergo genetic examination. Statistic data and our own experience show higher frequency of feminizing surgeries in such cases. The most difficult part of such surgeries proves to be the excision of genital cavernous bodies with clitoroplasty and clitoris translocation; the most responsible part in functional sense is vaginoplasty. Surgical treatment is not the final stage of treatment for such patients. Children with DSD require constant further dynamic checkups by gynaecologists, urologists, oncologists, endocrinologists, psychologists with relevant therapy correction. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local ethics committee of all participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: disorders of sexual development (DSD), hermaphroditism, feminizing correction.

Foetal phenotype of Maat-Kievit-Brunner type Ohdo syndrome

MED12 is a member of large Mediator complex; has a very crucial and central role in RNA polymerase II transcription; regulating cell signals involved in growth, development and differentiation. Different MED12 mutations may have different clinical presentation representing an allelic disorder. Maat-Kievit-Brunner (MKB) type Ohdo syndrome; has a typical facial features comprising of blepharophimosis, ptosis, long flat philtrum with thin vermilion, micrognathia with microstomia, scrotal hypoplasia with cryptorchidism, joint hypermobility with clinodactyly with overriding toes, A primigravida on antenatal ultrasound was detected to have growth restriction, corpus callosal dysgenesis, syndactyly and suspected ambiguous genitalia. Invasive testing and exome sequencing revealed hg19chrX:MED12:c.2315A>G: (p.Lys772Arg);MED12(NM_005120.3):c.2315A>G: (p.Lys772Arg) leading to provisional diagnosis of X linked Ohdo syndrome with an overlap with FG. Missense mutation was classified to be PM2; PP3 (ACMG) Clinical presentation, phenotype and mutational analysis led to provisional diagnosis of X linked Ohdo syndrome. Maat-Kievit-Brunner type of Ohdo syndrome is a rare condition and this is probably the first case describing foetal phenotype of MKB type of Ohdo syndrome.

Legal and Social Status of Eunuchs Islam and Pakistan

Media interest on eunuch and their problems has blossomed over the past decade. Stories about eunuchs have been the focus of dozens of books, movies, television dramas, and documentaries. Similarly, eunuchs now has moved from being a relatively obscure topic, Examined in a handful of medical journals, to becoming the central topic of numerous books and articles in a variety of disciplines, including psychology, history, anthropology, and medical ethics. Eunuchs now a day has also become a hot topic in legal circles. In the past ten years, more than a hundred legal articles and books have included a discussion on eunuchs and their problems. Most of these publications do not focus on the issues that have a direct effect on the lives of eunuchs.
 Understanding how the issues that are critical to people with such condition can be conflated with the issues affecting other people who challenge sex and gender norms requires a basic understanding of the nature of intersexuality. The meaning of the term eunuch has varied and the issue is still a topic of sometimes heated discussion. Although doctors and activists debate exactly what conditions qualify as to be called eunuch I am using the term in its broadest sense to include anyone with a congenital condition whose sex chromosomes, gonads, or internal or external sexual anatomy do not fit clearly into the binary male/female norm.
 Activists working to enhance the rights of eunuch’s advocate of eliminating harmful practices based on sex and gender stereotypes. In addition, both groups seek to enhance the right to sexual self-determination. The primary focus of each group differs, however. The primary goal of the eunuch’s movement is to eliminate or decrease the number of medically unnecessary genital surgeries being performed on children with an intersex condition. Intersex advocates believe that these medical interventions often result in physical and emotional trauma. Thus, they believe that these surgeries should not be performed on children and should only be undertaken with the informed consent of patient’s parents when they reach an age at which they can fully understand the risks and can decide for themselves whether they want to undergo genital surgery. The eunuch’s activist movement is still in its infancy and is in the process of developing its advocacy strategies.
 Although scholars in a variety of disciplines, including medical ethics, history, psychology, sociology, and anthropology, have published books on eunuchs, none has examined the role that the law can play in enhancing the lives of people with an intersex condition. The legal frameworks used by social justice movements that have effectively brought challenges to discriminatory practices and explores whether the eunuchs movement can form mutually beneficial alliances with these other movements and use similar legal strategies.

COG6-CDG: Expanding the phenotype with emphasis on glycosylation defects involved in the causation of male disorders of sex development.

This short report describes two 46,XY siblings of consanguineous parents manifesting a complex syndrome consisting of multiple dysmorphic features including growth and developmental retardation, gastrointestinal disorders, musculoskeletal and cardiac anomalies, as well as ambiguous genitalia (non-palpable testes, micropenis, underdeveloped scrotum). Whole exome sequencing revealed a homozygous novel splicing variant in the COG6 gene important for glycosylation.

Hypospadias

Hypospadias

SRY and NR5A1 gene mutation in Algerian children and adolescents with DSD and testicular dysgenesis.

In humans, sex determination and differentiation is genetically controlled. Disorders of sex development (DSD) result in anomalies of the development of the external and internal genitalia. Variants in transcription factors such as SRY, NR5A1 and SOX9, can cause changes in gonadal development often associated with ambiguity of the external genitalia. This study has been conducted to determine the frequency, types and associated genetic alterations in patients with DSD in the Algerian population. Thirty patients were included. Based on their clinical presentation, thirteen patients presented with ambiguous external genitalia, thirteen patients presented with hypospadias and four patients presented with bilateral undescended testes. Karyotype analysis was performed on peripheral blood lymphocytes using standard R-banding. DNA was isolated from blood leukocytes for PCR reaction and mutational analysis of SRY and NR5A1 was done by direct sequencing. Most patients with ambiguous genitalia had a 46,XY karyotype. One patient had a deletion of SRY, otherwise no point mutations in SRY or NR5A1 genes were identified. However, a single NR5A1 polymorphism (p.Gly146Ala) in patient with 46,XX DSD has been detected. The absence of mutations in these genes suggests that there are others genes playing an important role in sex development and differentiation.

PD15-01 KANK1 GENETIC AND GENOMIC ANOMALIES AFFECT GENITOURINARY (GU) DEVELOPMENT IN HUMANS

You have accessJournal of UrologyPediatric Urology I (PD15)1 Sep 2021PD15-01 KANK1 GENETIC AND GENOMIC ANOMALIES AFFECT GENITOURINARY (GU) DEVELOPMENT IN HUMANS Marisol O'Neill, and Dolores Lamb Marisol O'NeillMarisol O'Neill More articles by this author , and Dolores LambDolores Lamb More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001997.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: 9p24.3 is a chromosome hotspot for human GU anomalies with micro-deletions or -duplications associated with ambiguous genitalia and gonadal dysgenesis. One gene in 9p24.3, DMRT1, is needed for normal testicular fetal development. Using array comparative genomic hybridization (aCGH) together with retrospective literature/database analysis, locus mapping identified 60 patients with 9p24.3 CNVs of 37 duplications and 23 microdeletions. 50 of these patients had disorders of sexual differentiation, 7 had congenital anomalies of the kidney and urinary tract (CAKUT). We identified a second gene candidate in the minimal overlap region of 9p24.3 5' to DMRT1 that encompasses KN Motif and Ankyrin Repeat Domain Containing Protein 1 (KANK1). We used human and mouse models to test the hypothesis that genetic and genomic defects of KANK1 also resulted in anomalies of the external genitalia and CAKUT. METHODS: A mouse model of haploinsufficiency was generated using CRISPR-Cas9 to delete Kank1 and mice phenotyped. Penile and renal anomalies were defined by micro-CT analysis. Patients with upper and lower tract genitourinary birth defects underwent phenotypic analysis, genetic and genomic analysis by aCGH and whole exome sequencing. RESULTS: A mouse model of Kank1 haploinsufficiency exhibited renal dysfunction, penile anomalies and subfertility. KANK1 genetic variants were identified by Whole Exome Sequencing (WES) in patients with GU anomalies-2 had novel variants; one individual with an absent cervix, vaginal atresia and two novel variants resulting in nonsynonymous changes of two consecutive amino acids (p.C1187F and p.N118Y) both predicted to be deleterious. 14 individuals were identified with 10 rare variants, five of which (rs61737971, rs148744436, rs143675911, rs74458120, rs370051574) were present in individuals with CAKUT, renal insufficiency, focal segmental glomerulosclerosis, abnormal reproductive track development, hypospadias, bladder exstrophy- glomerular fibrosis, renal dysfunction, penile anomalies were also present in the Kank1 haploinsufficient mouse models. CONCLUSIONS: This study identifies a novel mechanism that underlies some GU birth defects which are usually surgically repaired with the etiology defined as idiopathic. This study identified renal dysfunction and a potentially severe kidney phenotype, as well as developmental anomalies of the penis caused by KANK1 haploinsufficiency in humans & mouse models. Source of Funding: T32 DK007763 (MO was a trainee) & R01DK078121 from NIDDK & Frederick J. and Theresa Dow Wallace Fund of the NY Community Trust (awarded to DJL) © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e272-e272 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Marisol O'Neill More articles by this author Dolores Lamb More articles by this author Expand All Advertisement Loading ...

Heterozygous variant in NR5A1 gene as a monogenic form of gonadal dysgenesis: a case report

NR5A1 gene mutations are associated principally to 46,XY DSD (Disorders of Sex Development), with an extensive range of phenotypic variability in patients, comprising gonadal dysgenesis and male infertility. NR5A1 gene plays a crucial role in reproduction, steroidogenesis, and sexual differentiation. The present case describes an Italian male adolescent with ambiguous genitalia at birth and a 46,XY karyotype who was investigated for DSD genetic panel conditions due to slow pubertal progression. A heterozygous variant in NR5A1 (NM_004959.4: c.937C>T, p.Arg313Cys) was identified in this patient and in his father. The same variant was previously described in other studies showing the wide heterogeneity of genotype-phenotype correlation in DSD patients.

A novel ARX loss of function variant in female monozygotic twins is associated with chorea

Pathogenic variants in ARX lead to a variety of phenotypes with intellectual disability being a uniform feature. Other features can include severe epilepsy, spasticity, movement disorders, agenesis of the corpus callosum, lissencephaly, hydranencephaly and ambiguous genitalia in males. We present the first report of monozygotic female twins with a de novo ARX pathogenic variant (c.1406_1415del; p. Ala469Aspfs*20), predicted to result in a truncated ARX protein missing the important regulatory Aristaless domain. The twins presented with profound developmental delay and seizures, consistent with the known genotype-phenotype correlation. Twin 2's features were significantly more severe. She also developed chorea; the first time this movement disorder has been seen in an ARX variant other than an expansion of the first polyalanine tract. Differential X-chromosome inactivation was the most likely explanation for the differing severities but could not be conclusively proven.

Formulation of Legal Provisions Concerning Gender Change

Sex change that is carried out through a medical process or commonly called sex change surgery, invites pros and cons in the community. The purpose of this study is to formulate regulations regarding the formulation of legal provisions regarding sex change that can reflect justice, benefit, and legal certainty as well as support the welfare of Transgender and Ambiguous Genitalia sufferers. This research is a normative legal research with philosophical, legislative, conceptual,case and comparative approaches. The analysis technique uses descriptive, comparative, evaluative and argumentative techniques. The results of the study indicate that the formulation of legal provisions regarding gender change is the use of the phrase the right to live in physical and spiritual prosperity in the formulation of legal norms as a large group that can reach various things, and the prohibition against plastic surgery to change identity, except for patients who have received court decision.

Congenital Urethrovaginal Fistula with Blind-Ending Vagina in a Female Pseudohermaphrodite Dog with Urinary Incontinence

An 8 mo old male Doberman pinscher was referred for investigation of persistent urinary incontinence. Physical examination revealed urine leakage and abnormal external genitalia. A computed tomography scan identified a large fluid-filled cavity extending from the caudoventral abdomen displacing the colon and urinary bladder. No retained testicles were identified. A retrograde urethrogram study found a linear communication, cranial to the pubic brim between the urethra to the fluid-filled cavity (fistula). Exploratory celiotomy was performed, and an entire female reproductive tract with a blind-ending vagina and a urethrovaginal fistula was found. En bloc gonad hysterectomy was performed, the fistula was transected, and a careful urethral reconstruction was performed. The urinary incontinence resolved immediately after surgery, and no complications were reported. Mild urinary incontinence recurred 4 days following patient discharge, and a urine bacterial culture was positive for Klebsiella spp. An antibiotic course was prescribed, and the incontinence fully resolved. Congenital urogenital abnormalities should always be considered in young animals presenting with urinary incontinence. Here, a young female pseudohermaphrodite dog with a naturally occurring congenital urethrovaginal fistula is described. Exploratory surgery was required for definitive diagnosis and surgical intervention yielded a good medium-term outcome with resolution of clinical signs.

Disorders of Sex Development.

Disorders of Sex Development.

Serum anti-Müllerian hormone concentration as a diagnostic tool to identify testicular tissue in canine disorders of sexual development

Disorders of sexual development (DSD) may have their origin in alterations of the chromosomal, gonadal or phenotypic sex. Affected animals are usually presented because of ambiguous external genitalia, seldom because of reproductive disorders. Anti-Müllerian hormone (AMH) is secreted in the gonads with higher amounts in males than in females and can be used to identify gonadal tissue in sexually normally developed dogs. The aim of this study was to examine the diagnostic potential of serum AMH to identify testicular tissue in 11 dogs with DSD. The diagnostic procedures applied were: determination of the phenotypic sex (n = 11), genital ultrasound (n = 9), determination of the SRY gene (n = 11), karyogram (n = 6), gonadectomy (n = 11), pathohistology of the gonads (n = 10), serum AMH measurement (n = 11). 39 female dogs described in a previous study and 19 male dogs with a normal spermiogram served as controls for the AMH serum concentrations in sexually intact dogs. The 11 dogs with DSD were classified as 7 XY DSD and 4 XX DSD. Presumptive testes were obtained in 10 dogs and 1 dog had an ovotestis combined with a testis. Mean serum AMH values of the dogs with DSD were significantly higher (P < 0.001) than in male and female controls. The upper limit of the AMH test (≥ 23ng/ml) was reached in 6 dogs. High AMH concentrations have been described previously in cryptorchid dogs. 1 dog with a male phenotype and 2 with a female phenotype had AMH values within the range of the male controls, although all of them had cryptorchid testes. A Poodle, in which epididymis were identified but no definitive gonads, had an AMH concentration of the lower limit of the test (≤ 0.01 ng/ml), comparable to previously described castrated dogs. This study indicates that serum AMH levels are a useful diagnostic tool to identify testicular tissue in dogs with DSD and suggests the possible use of AMH to diagnose testicular dysgenesis.