Zinner and Mayer-Rokitansky-Küster-Hauser syndromes: when unilateral renal agenesis meets genital anomalies

Abstract

Congenital unilateral renal agenesis is a relatively frequent condition at birth diagnosed mostly incidentally. Despite the excellent prognosis, unilateral renal agenesis is associated with an increased risk of other structural abnormalities, including genital malformations. The authors present two cases of asymptomatic adolescents with known congenital unilateral renal agenesis and associated genital malformations solely diagnosed during puberty—a man with Zinner syndrome and a female with Mayer-Rokitansky-Küster-Hauser syndrome.

Background

Zinner (ZS) and Mayer-Rokitansky-Küster-Hauser syndromes (MRKHS) can be asymptomatic until puberty, even though they can compromise reproductive health in adulthood. It is of extreme importance that the children born with unilateral renal agenesis maintain their imaging follow-up until puberty to exclude these anomalies by the time they start to be symptomatic.

Case presentation

Case 1

A 14-year-old man with a prenatal diagnosis of right kidney agenesis and no relevant family history for renal, urinary or genital abnormalities.

During the first 8 years of life, he was evaluated on nephrology consult with normal glomerular filtration rate, no hypertension and no urinary tract infections. By 7 years, pelvic ultrasonography (US) revealed a right mass, a ureterocele, surgically removed at that age.

By 14 years, he was without renal follow-up and his general practice referred him to a paediatric consultation for further evaluation. He was asymptomatic with an unremarkable general examination. He had never experimented any urinary tract infection or prostatitis. He denied any perineal discomfort or pain and he described ejaculation without pain or hematospermia.

Renal and pelvic US confirmed right renal agenesis, a left pyelocalyceal dilatation (12/13 mm) and seminal asymmetries (figure 1). MRI revealed dilatation of the right seminal vesicle ending to a seminal vesicle cyst (figure 2). Zinner syndrome (ZS) was diagnosed.

Figure 1.

Asymmetry of the right seminal vesicles, showing a structure that seems to correspond to the enlarged seminal vesicle measuring about 65 mm of greater longitudinal diameter. These changes are admitted to be in a probable relationship with the known congenital abnormalities that may involve the Wolffian ducts.

Figure 2.

Ectasia of the ejaculatory ducts of the seminal vesicles, conferring a ‘cystic’, polyploid and partially septate morphology to the seminal vesicles. This feature is more evident on the right side, although it is also evident a more discreet left ductal ectasia. These changes extend to the insertion of the drainage ducts of the seminal vesicles in the prostate.

Case 2

A 10-year-old woman with a prenatal diagnosis of right kidney agenesis was referred from her generalist due to uterine malformation suspicion. Family history was negative for infertility, renal, urinary or genital defects.

She was referred to a paediatric nephrologist at the age of 8 months. Full workup was normal, except for the presence of a single left kidney with compensatory hypertrophy. During the first years of life, she had not had urinary tract infections. She maintained a normal glomerular filtration rate, and no hypertension was found. She abandoned follow-up at the age of 2 years old.

By the 10 years of age, she was referred for further evaluation of an incidentally hydrometrocolpos suspicion in a renal and pelvic US, without any associated symptoms or any findings at the physical examination. MRI confirmed single left kidney with multilobular renal excretory cavities, left hemiuterus with normal size and morphology in continuity with one apparent normal cervix and a non-communicated right tubulouterine structure with homogeneous liquid content, suggesting an atrophic right hemiuterus with hematocolpos/hydrocolpos or an atrophic right kidney (figure 3). Laparoscopic exploration was performed: it confirmed bilateral normal ovaries and fallopian tubes, a right parauterine mass non communicating with the vagina and a tiny uterus on the left side communicating with the normal vagina. Parauterine mass was removed and right salpingectomy was performed.

Figure 3.

On the right side of the uterus is identified a tubular structure of homogeneous liquid content, closely related to the right lateral contour of the cervix, isthmus and uterine body. The superior contours are polyploid, which evokes the possibility of excretory renal ectasia, not excluding the possibility of this image correspond to an atrophic and dysmorphic right kidney with ectasia of the excretory system, located in ectopic topography in the pelvic cavity and adjacent to the uterine contour, making a differential diagnosis with hydrometrium and hydrocolpos in the right hemiuterus.

The girl was a 46,XX and she had renal agenesis combined with Müllerian duct anomalies. The diagnosis of an MRKHS type 2 was suspected.

Outcome and follow-up

Both patients presented normal pubertal development for sex and age.

Considering the male case, after multidisciplinary discussion, because of the relatively small size of the cyst and the absence of symptoms, a conservative treatment was decided, with an annual clinical and imaging control until adulthood.

The female patient had menarche at 12 years old (11 months after surgical intervention), she continues asymptomatic at 13 years old, with regular cycles without dysmenorrhoea or menorrhagia, and a clinical and imaging follow-up is performed annually.

Discussion

Congenital unilateral renal agenesis occurs in approximately 1:1300 births and due to its common asymptomatic course is usually diagnosed on the prenatal US as an incidental imaging.^{1 2} It is frequently associated with other abnormalities, including isolated or syndromatic anomalies of the cardiovascular, skeletal, central nervous and urogenital systems.^{1 3} Abnormalities of other organ systems occur in 30%–50% of patients with kidney and urinary tract anomalies and genital anomalies occur in 37%–60% of females and 12% of males with congenital unilateral renal agenesis.^{2 3}

Genital malformations associated with unilateral renal agenesis may be explained from an embryological perspective: the embryonic insult in the ureteral bud responsible for unilateral renal agenesis may also affect the Wolffian duct in males or the Müllerian duct in females, leading to malformations in both systems.²

ZS, first described in 1914 by Zinner, is a rare triad of Müllerian duct abnormality comprising unilateral renal agenesis, ipsilateral seminal vesicle cyst and ejaculatory duct obstruction.^{4 5}

Most patients are asymptomatic until the third or fourth decade of life and often manifest during the period of high sexual or reproductive activity.⁴ In asymptomatic patients, the seminal vesicle cyst is often less than 5 cm and it is discovered incidentally during cross-sectional imaging.⁴ Symptomatic patients can present dysuria (37%), frequency (33%), perineal pain (29%), epididymitis (27%) and painful ejaculation due to pressure of the seminal vesicle cysts.⁵ Later oligozoospermia and even azoospermia may develop, leading to infertility.⁵

Imaging enables accurate diagnosis of this anomaly. On US ipsilateral kidney is absent and the obstructed ejaculatory ducts are seen as anechoic structures in the pelvis. MRI is the modality of choice for precise delineation of the anatomy of the male genital tract and it is excellent for delineation of prostate and seminal vesicles and confirming that the cystic periprostatic structures are indeed within the seminal vesicles.^{4 5} MRI is also helpful for accurate preoperative surgical planning for seminal vesicle cyst excision whose realisation depends on the size and location of the cyst and presence of clinical symptoms.⁴

Surgical treatment of ZS provides an excellent cure and symptomatic relief (100% and 75%, respectively). Infertility resulting from ejaculatory duct obstruction is reversible by surgery and the long-term outcome is excellent.⁵

ZS is considered to be the male equivalent of MRKHS, defined as an aplasia/hypoplasia of the uterus and the upper two-thirds of the vagina in women who have normal development of secondary sexual characteristics and a 46,XX karyotype. The disorder is fairly common in women presenting with primary amenorrhoea (70%–80%).^4–8 If functioning endometrium is present, cyclical abdominal pain may be the presenting symptom. Subfertility and dyspareunia are other rare presentations.⁷

MRKHS affects at least 1 of 4500 women and congenital absence of the upper vagina and uterus is the prime feature of the disease. Since Wolffian and Müllerian ducts are contiguous, Müllerian abnormalities are common in girls with renal agenesis. Septate uterus is relatively common and can be associated with renal agenesis.^{3 6–8}

MRKHS is generally divided into three types: type 1 or typical (isolated symmetrical uterovaginal aplasia or hypoplasia) in 64% of the cases, type 2 or atypical (asymmetrical uterovaginal aplasia or hypoplasia, absence or hypoplasia of one or both fallopian tubes and malformation in the ovaries and/or the renal system) in 24% of the cases and Müllerian duct aplasia, renal dysplasia and cervical somite anomalies syndrome (uterovaginal aplasia or hypoplasia with malformations in skeletal or cardiac systems, muscular weakness and renal anomalies) in 12% of the patients.^{3 7 8}

US is the initial investigation of choice and MRI provides a more sensitive and specific means of diagnosis by allowing an accurate evaluation of the uterine aplasia with clear visualisation of the rudimentary horns and ovaries and is considered the gold standard for diagnosis of mullerian abnormalities.^6–8 Laparoscopic survey is applied in case of doubtful diagnosis after the realisation of non-invasive examinations.⁸ Management includes surgical treatment depending on the spectrum of congenital abnormalities of the vagina and the uterus and psychological support if infertility is a possibility.⁷

The prognosis and impact in fertility and sexual intercourse of women depend on the type of associated abnormalities. If the pain associated with functioning endometrial tissue is present, it can be treated successfully with laparoscopic resection of the abnormal uterus.⁶ When there is an abnormal vagina, plastic vaginal dilators can create a neovagina with high success rates. Laparoscopic vaginoplasty is a second-line option with anatomical and functional success in 98% and 97% of the cases, respectively.⁷ Infertility is one of the most feared complications of MRKHS and as the majority of the cases have preserved ovarian function, in vitro fertilisation should be considered.⁷ Psychological support plays a crucial role in the entire management due to its possible complexity.^6–8

Learning points.

• Unilateral renal agenesis can be associated with genital anomalies.

• Genital malformations associated with unilateral renal agenesis can be silent until puberty and the start of sexual activity and can lead to infertility.

• Children born with unilateral renal agenesis should maintain their imaging follow-up until puberty to exclude these genital anomalies by the time they start to be symptomatic.