Genital Tract Anomalies Research Articles

Eosinophilic chromophobe renal cell carcinoma in a child with hypospadias

Chromophobe renal cell carcinoma (CRCC) is a distinct variant of renal carcinoma generally affecting adults. We report a case of an unusual CRCC, arising in a male child affected by hypospadias. This case demonstrates that CRCC can occur in the pediatric patients and can be associated with genital tract anomalies such as Wilms tumor.

Strengths and weaknesses of in vitro assays for estrogenic and androgenic activity

The endocrine and reproductive effects of xenobiotics are believed to be due to (1) their mimicking the effects of endogenous hormones; (2) their antagonizing the effects of endogenous hormones; (3) their altering the pattern of synthesis and metabolism of natural hormones; and (4) their modifying hormone receptor levels. It has been suggested that endocrine disruptors may play a role in the decrease in human semen quantity and quality, an increase in the anomalies of male genital tract, and an increase in the testicular and breast cancer incidence during the last 50 years. Testing these hypotheses will require: (1) identifying estrogen and androgen agonists and antagonists among the chemicals present in the environment; (2) assessing the interactions among the endocrine disruptors to which humans are exposed; and (3) finding markers of estrogen (and androgen) exposure. The development of fast and sensitive bioassays is central to the achievement of these three goals.

Common congenital anomalies of the female genital tract

The impact of common congenital anomalies of the female genital tract is hugely variable. Some anomalies are asymptomatic chance findings requiring no intervention. Others have a major impact on the potential for sexual activity and fertility. A good knowledge of basic embryology is important to understand the pathogenesis and clinical features of these anomalies. All gynaecologists should be aware of these conditions and possible clinical presentations. Whilst some conditions, such as imperforate hymen require a simple surgical intervention, other more complex anomalies need careful assessment and accurate pre-operative assessment to optimise the long-term outcomes. The contribution of uterine anomalies to subfertility is poorly understood and the role of uterine surgery needs further research.

The pitfalls of vaginal construction

To evaluate a group of young women undergoing complex vaginoplasty, which may be defined as where there has already been previous complex pelvic surgery and the patient is unsuitable for conservative treatment or minor surgical revision. All patients who had undergone a complex vaginoplasty between 1997 and 2004 were reviewed retrospectively. Information was recorded on the underlying condition, previous surgery and preoperative assessment. The operative technique and complications were noted, and the outcome in terms of menstruation and sexual activity. In all, 15 patients fulfilled the criteria (mean age 22.2 years, range 17-36) and the mean follow-up was 4.75 (0.75-7) years. Fourteen patients had complex congenital anomalies of the lower genital tract and 11 of these had associated anomalies of the urinary and gastrointestinal system; four were XY females. The 15 patients had had 31 vaginal procedures, including ileal vaginoplasty, mobilization of perineal skin flaps and split-skin grafting. Three patients required osteotomies to increase pelvic outlet diameter. The commonest complications were stenosis (six patients) and fistula formation (four). Eight patients are now sexually active; the remaining seven have not attempted sexual intercourse. Complications are common and can be major; most patients require many repeat operations to achieve a patent vagina. Unfortunately at present, this is the only option for this group of young women to achieve a functional vagina. Patients with complex congenital anomalies of the reproductive and genital tracts are increasingly surviving into adulthood, and the numbers of these patients is likely to increase in the future.

Twenty-four new cases of WT1 germline mutations and review of the literature: genotype/phenotype correlations for Wilms tumor development.

We report here 24 new Wilms tumor (WT) patients with germline WT1 alterations and a synopsis of our own previously described and literature cases in whom age of tumor-onset, gender, and laterality were known. This combined database contains 282 patients, 117 patients with and 165 without WT1 germline alterations. Using this information we have determined the median age of tumor-onset for patients with (12.5 months) and without WT1 gene alterations (36 months). The earliest onset was in patients with truncation (12 mo, 66 patients), followed by missense mutations (18 mo, 30 patients) and deletions (22 mo, 21 patients). Patients with the two most frequent nonsense mutations R362X and R390X and the Denys-Drash syndrome (DDS) hot spot mutation R394W/Q/L had a very early onset (9, 12, and 18 mo, respectively). The highest number of bilateral tumors was observed in the group of truncation mutations, with a higher percentage of bilateral tumors when truncations occurred in the 5' half of the WT1 gene. In addition to genital tract anomalies (GU), early onset nephrotic syndrome with diffuse mesangial sclerosis and stromal-predominant histology, tumor bilaterality, and early age of onset can now be added to the list of risk factors for carrying a germline WT1 mutation.

Ultrasound of female genital anomalies.

Congenital anomalies of the female genital tract result from müllerian duct anomalies and/or abnormalities of the urogenital sinus or cloaca. Due to the close developmental relationship between the genital and the urinary tracts, association of anomalies in both systems are common. This article reviews the appearance of developmental anomalies of the female urinary and genital tracts and points out common associated malformations to allow an early and complete sonographic assessment of affected infant.

Müllerian anomalies.

The reproductive organs in both males and females consist of gonads, internal ductal structures, and external genitalia. Normal sexual differentiation is dependent on the genetic sex determined by the presence or absence of the Y chromosome at fertilization. Testes develop under the influence of the Y chromosome and ovaries develop when no Y chromosome is present. In the absence of testes and their normal hormonal products, sexual differentiation proceeds along the female pathway, resulting in a normal female phenotype. Anatomic gynecologic anomalies occur when there is failure of normal embryologic ductal development. These anomalies include congenital absence of the vagina as well as defects in lateral and vertical fusion of the Müllerian ducts. Treatment of müllerian anomalies begins with the correct identification of the anomaly and an understanding of the embryologic origin. This includes evaluation for other associated anomalies such as renal or skeletal abnormalities. After correct identification, treatment options include nonsurgical as well as surgical intervention. This chapter serves to review the embryology and development of the reproductive system and to describe common genital tract anomalies. Details of surgical or nonsurgical correction of these anomalies are presented.

Delayed Puberty and Amenorrhea

The ability to diagnose and manage disorders that cause delayed puberty requires a thorough understanding of the physical and hormonal events of puberty. Wide variation exists within normal pubertal maturation, but most adolescent girls in the United States have begun to mature by the age of 13. Delayed puberty, a rare condition in girls, occurs in only approximately 2.5% of the population. Constitutional delay, genetic defects, or hypothalamic-pituitary disorders are common causes. Amenorrhea, often found as a symptom of delayed puberty, may be due to congenital genital tract anomalies, ovarian failure, or chronic anovulation with estrogen presence or with estrogen absence.

Index of Suspicion

Index of Suspicion

Anal atresia, vertebral, genital, and urinary tract anomalies: a primary polytopic developmental field defect identified through an epidemiological analysis of associations.

Anal atresia (AA) is observed per se or as part of different Mendelian or chromosomal syndromes, and as part of the VACTERL primary developmental field, CHARGE association, cloacal extrophy, in a mitochondrial cytopathy, and other multiple congenital anomaly patterns. There are only a few studies on the defects associated with AA, and in all of them it was observed that genitourinary defects are most frequent in infants with AA. Here we present the analysis of 28,410 malformed infants to study the frequency of 11 selected congenital defects in infants with AA in relation to their frequency in infants with multiple congenital anomaly patterns without AA. We conclude that the association of AA + spine defects + renal/urinary tract defects + genital defects constitutes a group of defects that tends to be present together in the same child because they are pathogenetically related, and since they are of blastogenetic origin they constitute a primary polytopic developmental field defect.

Development of the fetal uterus between 19 and 38 weeks of gestation: in-utero ultrasonographic measurements.

In-utero assessment of the internal female genitalia is important for determination of fetal gender in fetuses with suspected genital tract anomalies. We therefore measured fetal uterine transverse width and circumference from 19 weeks of gestation until term, using transvaginal and transabdominal high-resolution ultrasound techniques in order to establish nomograms. A prospective, cross-sectional study on 180 normal singleton pregnancies was performed. Data were obtained for 140 normal fetuses. The mean +/- SD uterine width and circumference were 12.9 +/- 4.1 mm (95% confidence interval 12.1-13.7), and 40.2 +/- 12.5 mm (95% confidence interval 37.9-42.5) respectively. Uterine size as a function of gestational age was expressed by the regression equations: uterine width (mm) = 12.9 + 0.7 x gestational age (weeks), and uterine circumference (mm) = 40.2 + 2.1 x gestational age. The correlation coefficients, r = 0.885 and r = 0.888, for uterine width and circumference, by gestational age respectively, were highly statistically significant (P < 0.001). A nomogram of uterine width and circumference per gestational week, and the 95% prediction limits were defined. The present data offer baseline measurements of the fetal uterus that may allow intrauterine assessment of the female genital tract and associated fetal gender.

Unilateral Invasive Adenosquamous Carcinoma of the Cervix in a Uterus Didelphys

Congenital anomalies of the female genital tract are not uncommon but may be missed by a less than careful clinical examination. We describe a case of unilateral invasive adenosquamous carcinoma of the cervix in a uterus didelphys. The diagnosis of didelphys was not made until the patient's surgical consultation. Failure to appreciate the presence of a second cervix may have contributed to a delay in diagnosis and to the late stage at presentation. (J GYNECOL SURG 12:213, 1996)

Congenital genitourinary anomalies. Is there a predilection for multiple primary malignant neoplasms?

A case of simultaneous uterine and renal cell carcinoma in an elderly woman who had a septate vagina, double cervix, uterus didelphys, and a single kidney secondary to contralateral renal agenesis is reported. She was treated for a period of 8 months, first with pelvic irradiation followed by total abdominal hysterectomy and bilateral salpingo-oophorectomy and subsequently with heminephrectomy. Her renal function was normal postoperatively. The patient died of congestive heart failure in June 1990 after being free of carcinoma for approximately 18 years. The authors believe that this is the only case of its kind currently reported in the literature. Four of her family members died of either gastric (n = 3) or lung (n = 1) cancer, and one sister is alive with colon cancer. Only 19 proven cases of this constellation of congenital anomalies have been reported in the literature, and none have been associated with genitourinary (GU) carcinomas. There is a 50% to 70% incidence rate of genital tract anomalies in female patients with unilateral renal agenesis, secondary to the intimate association of the mesonephric and müllerian ducts. It has been suggested that the GU tract is prone to multiple primary malignant neoplasms, and there are families genetically predisposed to the development of large bowel and GU carcinomas. No conclusions can be drawn concerning the development of carcinoma in patients with congenital GU anomalies because of the small number of patients and the lack of follow-up in the literature.

Vaginal Dystocia in a Patient with a Double Uterus and a Longitudinal Vaginal Septum

A case of a breech straddling a vaginal septum requiring urgent division is reported. This case demonstrates some of the obstetric complications associated with congenital genital tract anomalies.

The Imperforate Hymen: A Culturally Oriented Surgical Approach

ABSTRACT Virginity is considered very highly in the Islamic and Arabic culture. It denotes chastity and a good upbringing. Because of this, a family with a girl afflicted with imperforate hymen is ...

Müllerian Anomalies and Renal Agenesis: Autosomal Dominant Urogenital Adysplasia

We report two families in which mullerian anomalies or renal agenesis appeared to be caused by an autosomal dominant gene that produces unilateral or bilateral renal agenesis and a spectrum of mullerian anomalies. This single gene disorder may account for the high incidence of mullerian anomalies observed in females with bilateral renal agenesis and the increased frequency of renal anomalies in patients with mullerian malformations. The range of mullerian anomalies in this disorder includes bicornuate uterus, uterus didelphys, Rokitansky- Kuster -Hauser syndrome (vaginal atresia with or without absence of the uterus), and total mullerian aplasia. Gene expression is not sex limited. Affected males can have bilateral or unilateral renal agenesis, and possibly may have unilateral or bilateral absence of the vas deferens or seminal vesicles. We suggest that autosomal dominant urogenital adysplasia is common, but underdiagnosed because of the deceptive variability in gene expression. In addition, reduced gene penetrance and reduced biologic fitness from lethal renal anomalies or genital tract anomalies may obscure the autosomal dominant nature of this disorder in most families.

The genital tract in female children with imperforate anus

A retrospective study was undertaken to determine the type and frequency of genital tract anomalies that occur in female children with imperforate anus. The functional outcome and optimal management of the genital tract anomalies were also studied. Primary vaginal anomalies occurred in 22 of 72 patients assessed, and uterine anomalies occurred in 18 of 51 patients assessed. For 17 patients, who were 13 years of age or older, information was available on genital tract function. Of these 17 patients, five had severe vaginal scarring. A previous vaginoplasty or cloacal abnormality was a predictor of poor vaginal function. It is suggested that vaginoplasty, in cases in which it is possible, be delayed until puberty.

Müllerian anomalies and renal agenesis:Autosomal dominant urogenital adysplasia

We report two families in which müllerian anomalies or renal agenesis appeared to be caused by an autosomal dominant gene that produces unilateral or bilateral renal agenesis and a spectrum of müllerian anomalies. This single gene disorder may account for the high incidence of müllerian anomalies observed in females with bilateral renal agenesis and the increased frequency of renal anomalies in patients with müllerian malformations. The range of müllerian anomalies in this disorder includes bicornuate uterus, uterus didelphys, Rokitansky- Kuster -Hauser syndrome (vaginal atresia with or without absence of the uterus), and total müllerian aplasia. Gene expression is not sex limited. Affected males can have bilateral or unilateral renal agenesis, and possibly may have unilateral or bilateral absence of the vas deferens or seminal vesicles. We suggest that autosomal dominant urogenital adysplasia is common, but underdiagnosed because of the deceptive variability in gene expression. In addition, reduced gene penetrance and reduced biologic fitness from lethal renal anomalies or genital tract anomalies may obscure the autosomal dominant nature of this disorder in most families.

Upper genital tract abnormalities and pregnancy outcome in diethylstilbestrol-exposed progeny

Previous studies have suggested that there is an association between genital tract abnormalities and pregnancy outcome in women exposed to diethylstilbestrol (DES) in utero. In a collaborative study, 676 DES-exposed women had hysterosalpingographic examinations, and the findings were related to the outcome of pregnancy in 327 of these women. The findings revealed that (1) there is a considerable variation of frequency of different types of upper genital tract anomalies in women from different sources and with different motivations for enrollment in the study, (2) the presence of structural cervical changes and vaginal epithelial changes are markers for the likelihood of abnormalities in the uterine fundus, (3) women with upper genital tract abnormalities have increased odds for poor pregnancy outcome as compared to women with normal hysterosalpingographic findings, and (4) although some abnormalities were most often or consistently associated with poor pregnancy outcome, no specific changes could be related to specific types of pregnancy outcomes.

Some experiences in the diagnosis and treatment of congenital anomalies of the female genital tract

Some experiences in the diagnosis and treatment of congenital anomalies of the female genital tract