Gonadal Agenesis Research Articles

Criptorquidismo unilateral abdominal em felino

During embryogenesis, the testes and ovaries form caudally to the kidneys. In males, the testes descend into the intrauterine scrotal sac. The absence of two testes in the scrotal sac after six months of age may indicate conditions such as testicular agenesis or cryptorchidism. In felines, cryptorchidism is rare (1-8%) compared to dogs (7-9%). Diagnosis involves anamnesis, palpation and abdominal ultrasonography, which is crucial in locating the testicle and planning for surgery. This case report describes a one-year-old male cat with unilateral abdominal cryptorchidism, which was successfully resolved through exploratory laparotomy and orchiectomy. The case highlights the importance of ultrasonography for the diagnosis and treatment of this condition.

A RARE CASE OF OVARIAN AGENESIS AND HYPOPLASTIC UTERUS IN A PREPUBERTALGIRL WITH NORMAL 46, XX KARYOTYPE

Delayed onset of puberty and primary amenorrhea pose diagnostic challenges, often associated with diverse etiologies including hypothalamic-pituitary disorders, gonadal dysgenesis, and müllerian duct malformations.Historically, such syndromes have been associated with XY chromosomal components, but rare cases in karyotypically normal females (46, XX) have been reported. Comparisons with similar cases, including atypical forms of Mayer-Rokitansky-Küster-Hauser (MRKH) syndromeare made, highlighting the rarity of this condition. Despite advancements, the genetic basis remains unspecified, underscoring the need for further research. We present a unique case of gonadal agenesis and hypoplastic uterus in a 46,XX individual, without associated organ system anomalies, contributing to primary amenorrhea. Diagnostic evaluations including hormonal assessment, and pelvic MRI confirmed the absence of ovaries and severe hypoplasia of paramesonephric duct (PMND) derivatives. Treatment with 17beta estradiol successfully induced puberty, highlighting the clinical importance of timely intervention. Early detection of such cases is crucial for providing comprehensive support and improving patient outcomes.

A rare case of Zinner syndrome with unilateral testicular agenesis and aberrant course of left common iliac artery

BackgroundZinner syndrome is a rare Wolffian duct anomaly presenting as a triad of unilateral renal agenesis, ipsilateral seminal vesicle cyst and ipsilateral ejaculatory duct obstruction. The condition is due to a developmental anomaly leading to malformation of the mesonephric duct. Magnetic resonance imaging is considered to be the gold standard for the diagnosis of Zinner syndrome. Due to the limited number of cases reported in the literature, the associations of Zinner syndrome are not well established. Case presentationIn this case report, we are presenting a case of a 38-year-old male with dysuria, intermittent pain in the scrotum and lower abdomen and painful ejaculation for the past six months. Imaging findings led to the diagnosis of Zinner syndrome, with unilateral testicular agenesis and an aberrant course of the left common iliac artery.ConclusionsApart from the known associations of Zinner syndrome, testicular agenesis in a patient with Zinner syndrome has not been reported in the literature and is an important addition to the limited literature available.

Update on canine anorchia: A review.

Abnormalities of the external genitals are an important issue in dog breeding because of the unfavourable qualities and characteristics of breeds, resulting in consistent economic losses. Despite their significance, little scientific attention has been given to these problems. Although there are several reviews on cryptorchidism in dogs, none have described anorchia. Testicular agenesis is a rare reproductive disorder with a congenital origin. Moreover, no author has described the diagnostic procedure for making a definitive diagnosis of anorchia in dogs. It is important to have a well-structured diagnostic scheme to help practical veterinarians make a confirmatory diagnosis. This review article aims to provide an update on canine anorchia diagnosis based on the poor research studies published in recent years. We have also contributed to the pathogenesis of this disorder using human medicine studies. Finally, the review includes therapeutic hypotheses that can be expanded in future studies.

Deletion of Wt1 during early gonadogenesis leads to differences of sex development in male and female adult mice.

Assessing the role of the WT1 transcription factor (WT1) during early gonad differentiation and its impact on adult sex development has been difficult due to the complete gonadal agenesis and embryonic lethality exhibited by Wt1KO mouse models. Here, we generated Wt1LoxP/GFP;Wt1Cre mice, the first Wt1KO mouse model that reaches adulthood with a dramatically reduced Wt1 expression during early gonadogenesis. Wt1LoxP/GFP;Wt1Cre mice lacked mature gonads and displayed genital tracts containing both male and female genital structures and ambiguous genitalia. We found that WT1 is necessary for the activation of both male and female sex-determining pathways, as embryonic mutant gonads failed to upregulate the expression of the genes specific for each genetic programme. The gonads of Wt1LoxP/GFP;Wt1Cre mice showed a lack of production of Sertoli and pre-granulosa cells and a reduced number of germ cells. NR5A1 and the steroidogenic genes expression was modulated differently in XY and XX Wt1LoxP/GFP;Wt1Cre gonads, explaining the mutant phenotypes. Further studies of the XX Wt1LoxP/GFP;Wt1Cre gonads revealed that deletion of WT1 at an early stage impaired the differentiation of several cell types including somatic cells and the ovarian epithelium. Through the characterisation of this Wt1KO mouse model, we show that the deletion of Wt1 during early gonadogenesis produces dramatic defects in adult sex development.

078 A rare case of Mayer-Rokitansky-Küster-Hauser syndrome associated with bilateral ovarian agenesis in a normal karyotypic female

Objective: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is the second more common cause of primary amenorrhea resulting from congenital absence of the vagina and agenesis or hypoplasia of the Mullerian (paramesonephric) ducts. Patients with MRKH syndrome have normal functioning ovaries with normal 46, XX karyotype and undergo puberty. On the contrary bilateral gonadal agenesis is a rare cause of hypergonadotropic hypogonadism. Combination of these two pathologic entities is sporadically reported in the literature. We present an extremely rare case of primary amenorrhea with MRKH syndrome (U5bC4V4 by ESHRE classification) and coexisting bilateral ovarian agenesis.

ANDROGEN INSENSITIVITY SYNDROME – A CASE REPORT

Background: AIS is one of the most commonly diagnosed XY DSD, with an estimated prevalence of 2:100.000 to 5:100.0001 and an incidence of 1:20.0002 to 1:99.0003. The name testicular feminization syndrome was coined by John McLean Morris of Yale University in 1953. The first description of this syndrome dates back to 1817, as quoted by Morris 4. It is the third most common cause of primary amenorrhea after gonadal dysgenesis and Mullerian agenesis 5.
 Case Report and Discussion: A 15-year-old phenotypic girl was evaluated for primary amenorrhea to find Complete Androgen Insensitivity Syndrome (CAIS) and underwent bilateral orchidectomy with plan for vaginoplasty at AIMSR, Hyderabad.
 Review of Literature: The treatment of AIS is based on the reinforcement sexual identity, gender identity plan and hormone replacement therapy. The prognosis is good, if the testicular tissue is resected at proper time.
 Conclusion: CAIS should be considered as important differential diagnosis in delayed menarche while evaluation for primary amenorrhea and early gonadectomy can avoid gender identity disorder (GID) / psychological issues
 Keywords: CAIS, GID

A Case Report: Challenge in Treatment of a Rare Condition of Gonadal Agenesis and Bipolar Disease

A Case Report: Challenge in Treatment of a Rare Condition of Gonadal Agenesis and Bipolar Disease

Coexistence of Gonadal Dysgenesis and Mullerian Agenesis in a Female with 46 XX Karyotype: A Case Report

Gonadal dysgenesis is a rare genetically heterogeneous disorder characterized by underdeveloped ovaries with consequent, impuberism, primary amenorrhea, and hypergonadotropic hypogonadism. Mullerian agenesis or Mayer‑Rokitansky‑Kuster‑Hauser syndrome is characterized by congenital aplasia of the uterus and the upper part (2/3) of the vagina in a woman with normal development of secondary sexual characteristics and a normal 46 XX karyotype. The association of gonadal dysgenesis and Mayer-Rokitansky-Kuster-Hauser syndrome is very rare and appears to be coincidental. We report a case of a 24-years old woman who presented with primary amenorrhea. The endocrine study revealed hypergonadotrophic hypogonadism. The karyotype was normal, 46,XX. Internal genitalia could not be identified on the pelvic ultrasound and pelvic MRI. There were no other morphological malformations. Keywords: Gonadal dysgenesis; Mayer Rokitansky Kuster Hauser syndrome; Mullerian agenesis; primary amenorrhea; 46,XX.

Long-term outcome in a case series of Denys-Drash syndrome.

BackgroundDenys–Drash syndrome (DDS) is a rare disease caused by mutations in exons 8 and 9 of the WT1 gene. It is characterized by the association of early onset steroid-resistant nephrotic syndrome (SRNS), Wilms’ tumour and, in some patients, intersex disorders, with increasing risk of gonadoblastoma. There are few published data concerning the long-term outcome of patients with DDS. The aim of this study was to report our experience. MethodsData were collected from five children (three boys) with confirmed DDS diagnosed from 1996 to 2017. The mean follow-up of these patients was 16 years.ResultsThe patients presented with SRNS and diffuse mesangial sclerosis at renal biopsy. All patients were hypertensive and progressed to end-stage kidney disease, initiating dialysis at a mean age of 28 months. Three patients developed Wilms’ tumour 9 months after the SRNS was identified, which was treated by nephrectomy and chemotherapy. All five patients received kidney transplantation. SRNS did not recur after transplantation in any of the patients and graft survival was similar to that of other kidney transplant recipients in our programme. All three boys had ambiguous genitalia and cryptorchidism but a confirmed male karyotype (46, XY). One girl presented with gonadal agenesis, whereas the other one had normal female ovarian tissue and external genitalia. Both girls had a female karyotype (46, XX). Gonadoblastoma was not observed at any case.ConclusionsEarly DDS recognition in patients with SRNS is crucial due to its low prevalence, the specific treatment approach required and early detection of Wilms’ tumour. Few data are available regarding long-term outcomes.

Ovarian agenesis and Mullerian duct dysgenesis in a karyotypically normal (46, XX) pre-pubertal girl with aberrant cognition: A case report and literature review

Introduction: Phenotypically normal pre-pubertal girl presenting with only a little delay in onset of puberty and emotional lability is seldom thought to be suffering from a serious underlying congenital defect at the outset. Amongst different congenital causes for such presentation, Mayer-Rokitansky-Kuster-Hauser syndrome is scarcely reported so far. This condition usually manifests with primary amenorrhoea and infertility in phenotypically and karyotypically normal 46, XX females. In the atypical form of this syndrome additional congenital malformations involving mostly renal and skeletal systems are noticed along with Mullerian dust dysgenesis. Case description: A 12-year-old girl attended the adolescent clinic with complaints of generalised weakness, inadequate height gains and emotional lability. Initial clinical examination recorded genu valgus and absence of pubertal growth spurt. Subsequently, blood hormonal assay depicted hypergonadotropic hypogonadism state. Bilateral absence of gonads and Mullerian duct anomalies were detected further in an otherwise normal female karyotype (46, XX). No additional structural anomaly noticed. Developmental quotient assessment suggested intellectual disability. Conclusions: A stepwise approach incidentally revealed a rare condition like atypical form of MRKH syndrome where bilateral gonadal agenesis and Mullerian duct dysgenesis were present but without any additional congenital malformations. Assessment of cognitive function in such cases should be sought for. Early detection of such rare case helps in building the emotional support of the family members in advance, long before the time when the patient might eventually present with primary amenorrhoea or infertility.

The spectrum of 45,X/46,XY mosaicism in Taiwanese children: The experience of a single center.

45,X/46,XY mosaicism is a rare sex chromosome abnormality. Here, we present our experience in the management of 45,X/46,XY Taiwanese children. We enrolled 19 patients from January 1981 to September 2016. The diagnosis of 45,X/46,XY mosaicism was made by karyotyping peripheral blood lymphocytes. All medical records were thoroughly reviewed. Of the 19 patients, 16 were reared as females and 3 as males. The age at diagnosis ranged from 1 month to 15 years and 9 months. Atypical genitalia, short stature, and Turner stigmata were common manifestations. No patient exhibited a cardiac malformation but 29% had renal malformations and 12.5% had autoimmune thyroid disease who developed thyroid dysfunction later. Nine girls with short stature received growth hormone therapy and their height standard deviation score rose from -3.4±1.1 to -1.4±0.9 in adulthood (P<0.01). The gonadal phenotypes included bilateral streak gonads in nine patients, a streak gonad with contralateral gonadal agenesis in one, mixed gonadal dysgenesis in five, bilateral dysgenetic testes in two, and bilateral gonadoblastomas in one. The 45,X/46,XY phenotype varies widely and a high index of suspicion is important to ensure early diagnosis. Cardiac and renal malformations should be screened ultrasonically at diagnosis and thyroid status should be monitored annually. Growth hormone effectively improves adult height in short girls. Prophylactic gonadectomy is indicated for those with intra-abdominal streaks or dysgenetic gonads to prevent the development of a malignancy.

Mullerian Agenesis in One of the Non-Identical Twins: A Case Report and Literature Review

Mullerin agenesis also referred as mullerian aplasia, Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKH) or vaginal agenesis is the congenital anomaly of vertical fusion defect of mullerian system resulting in variable abnormalities of female reproductive tract with normal functioning ovaries. It is second most common cause of primary amenorrhea after gonadal agenesis. The occurrence of mullerian agenesis in twins is very rare. We present the case of one of the non-identical twins, 22 years female, with primary amenorrhea. Her elder twin sister had a normal female reproductive system. In our case, diagnosis was supported by presence of definitive primary amenorrhea with well-developed secondary sexual characteristics. Normal physiological hormonal levels ruled out the ovarian or pituitary pathology. Imaging studies like ultrasonography and magnetic resonance imaging (MRI) provided additional confirmation.

Treatment of impalpable testis - one clinic's experience.

IntroductionUndescended testes are recognised in 1% to 2% of boys during the first year of life, and about 20% of them are impalpable. Ultrasonography (US) may establish the localisation of the testis but the final diagnosis is usually determined laparoscopically.AimTo evaluate long-term results of laparoscopic treatment of boys with impalpable testes and sensitivity of preoperative ultrasound.Material and methodsBetween 2011 and 2015, we operated on 545 boys with undescended testes. Sixty-two of them with 65 impalpable testes were treated laparoscopically – the study group. Mean age was 3.5 years. The study group was divided into 5 groups according to type of treatment. The volume and position of the operated gonad were assessed manually and by ultrasound.ResultsIn group 1 testicular agenesis was observed in 19 patients. In group 2 revision of the inguinal canal revealed testicular agenesis in 7 and atrophy in 4 patients. In group 3 conversion to classic orchiopexy was performed in 10 patients. In group 4 one-stage orchiopexy was performed in 9 patients on 12 testes. In group 5 a two-stage F-S procedure was performed in 13 patients. Ten testes in group 4 had a volume in the normal range (84%) and also 10 testes in group 5 (77%).ConclusionsLaparoscopy in impalpable testes is the procedure of choice and allows definitive management, even when conversion to open procedure is necessary. Sensitivity of preoperative ultrasound is generally about 60% for true intra-abdominal testes, so diagnostic laparoscopy is necessary.

Femoral hypoplasia- unusual facies syndrome: A case report and literature review

The femoral hypoplasia- unusual facies syndrome (FH/ UFS); also known as femoral facial syndrome (FFS), is a rare condition characterized by a variable degree of unilateral or bilateral femoral hypoplasia associated with facial anomalies.The two principal characteristics of this syndrome, micrognathia and shortened femur, can be demonstrated by sonographic (US) imaging in the early stages of pregnancy. This disorder was first discovered by Daentt et al in 1975 and is more common in females. The femoral hypoplasia- unusual facies syndrome is a rarely considered clinical entity that has a strong association with maternal diabetes.This report describes a case of FH/ UFSfollowed in our Physical and Rehabilitation Medicine (PRM) departmentfor proximal bilateral femoral agenesis.Hehad facial dysmorphia, bilateral testicular agenesis with a rare finding like bilateral second toe supraductus.

Novel Heterozygous Genetic Variants in Patients with 46,XY Gonadal Dysgenesis.

46,XY gonadal dysgenesis (GD) constitutes a rare group of disorders characterized by the presence of dysfunctional testes in genotypic males. The molecular etiology is not known in about 2 thirds of instances. The aim of this study was to identify the genetic cause in patients with 46,XY gonadal dysgenesis. Based on clinical, cytogenetic, and biochemical screening, 10 patients with 46,XY GD were recruited. Direct sequencing of SRY, NR5A1, SOX9, DAX1, DHH, DMRT1 genes was carried out for molecular analysis. Among 10 patients, 5 were diagnosed with complete gonadal dysgenesis (CGD), 3 with partial gonadal dysgenesis (PGD), and 3 with testicular agenesis. Molecular analysis revealed 12 heterozygous genetic changes, 4 of which were novel. One (c.416T>A) was observed in evolutionary conserved region of DMRT1 gene in a patient with CGD and was found to be probably damaging on in silico analysis. Other 3 were identified in NR5A1 gene (c.990+22 C>A, c.1387+1403T>A and p.131P), but their association with gonadal dysgenesis is not evident from our study. These genetic changes were absent in parents and 50 healthy control samples, which were also studied. With targeted sequencing approach, a molecular diagnosis was made in only one patient with 46,XY GD. The application of new genomic technologies is required for the precise evaluation of these rare genetic defects.

Bilateral proximal femoral agenesis: Case report

The femur aplasia is a congenital developmental defect of the femur often associated with malformations of the pelvis and lower limb. There are all intermediaries between the short femur and vestigial femoral. The total femur absence (agenesis) is rare. We report a case of a child followed in our Physical Medicine Department for proximal bilateral femoral agenesis. This is M.S., a 5 years old child, addressed for a waddling gait and a deformation of the trunk. He is issued from a consanguineous marriage. His mother, 45 years old, diabetic under oral antidiabetic agents with notion of non-switch to insulin treatment at the start of pregnancy. The psychomotor development was normal except for a delay in walking (around the age of 2 years). Clinical examination found a small height (88 cm) and a weight of 23 kg. On spine examination, the occipital axis is diverted to the right with a left small dorsal gibbosity and lumbar lordosis. He also had an unequal length of lower limbs of 1 cm from the right side. Moreover, the child had bilateral testicular agenesis confirmed by ultrasound. The radiological assessment concluded to agenesis of the two femurs and absence of scoliosis. The patient benefited from functional rehabilitation sessions while the surgery was not indicated. Maternal diabetes is known to have teratogenic effects such as heart defects, kidney abnormalities but also femoral agenesis. There are few cases reported in the literature, where the originality of our case.

Description of Clinical and Surgical Aspects of Four Cases of Lip Commissure to Eyelid Transposition for Repair of Eyelid Coloboma in Cats

Background: Eyelid coloboma or eyelid agenesis is the most common congenital disease in cats. It can affect both the upper and the lower lids and is commonly bilateral. This congenital defect has been reported in several breeds, such as Persian and Domestic Short-Haired Cat. Generally, this defect results in inversion of the colobomatous eyelid, which can cause trichiasis and inflammatory keratitis and corneal ulceration. The only effective treatment is blepharoplasty. This paper describes the clinical and surgical aspects of four patients treated by lip commissure to eyelid transposition for the repair of eyelid coloboma using the technique described in 2010. Results of this procedure have never been reported in Brazil. Cases: Seven eyes of four cats presenting eyelid coloboma affecting up to two thirds of the eyelid were evaluated in this study. Two of the four cats were males and two were females; their average age was 3 years. All patients were admitted at the same institution, and the main issues were purulent discharge and impaired vision. Diagnosis was based on physical and ophthalmic examination. Non-ulcerative keratitis was present in all cases. Corneal ulcer was diagnosed in three patients by the fluorescein dye test. In two cats, a corneo-conjunctival dermoid was found at the temporal-dorsal region of one eye, and measured approximately 0.3 mm; and the other two exhibited microphthalmia in one eye. No abnormalities were seen in the anterior chamber, lens, and vitreous. One of the cats exhibited retinal detachment, and one exhibited testicular agenesis, both of the abnormalities diagnosed by ultrasound. Complete blood count and biochemical tests were performed in all patients before general anesthesia for the corrective procedure. Before surgery, eyes with ulcerative and non-ulcerative keratitis were treated with topical antibiotics and lacrimommimetics. In the 7 eyes, lip commissure to eyelid transposition technique was used for correction of the colobomatous defect. The procedure consisted of a mucocutaneous flap that simulates a natural eyelid. Corneo-conjunctival dermoids were also removed at the same time by superfcial keratectomy. In the postoperative period, all patients received oral non-steroidal antiinflammatory drug and an antibiotic, as well as cleansing of the surgical wound. All patients exhibited improvement of corneal abnormalities following one week of the procedure. However, three cats had suture dehiscence on the lip commissure, which healed by secondary intention after a week. Two weeks after surgery, superfcial necrosis was observed at the tip of the edge of the transplanted flap, in all cats. In order to promote healing, the necrotic edges were debrided at the time of sutures removal, 10 to 15 days after surgeries; at this time, both lip commissure and eyelid wound had already healed. Facial distortion was presente owing to skin overlapping on the site of the flap. All patients had their ability to blink restored, and there was absence of trichiasis on the flap. However, three cats had thichiasis caused by retraction of the pre-existing eyelid at the medial canthus. Discussion: Good functional and esthetic results were achieved, similarly to those previously described, which allows us to consider that this technique is appropriate for eyelid reconstruction in eyelid coloboma or agenesis cases. Nevertheless, this procedure can have some complications, such as suture dehiscence, facial deformity, superfcial necrosis of the edges of the flap, and trichiasis of the pre-existing eyelid of the medial canthus. To overcome these issues, authors suggest removal of the skin under the flap to decrease facial distortion, and removal of the whole pre-existing eyelid, in order to avoid trichiasis caused by retraction of this tissue. Keywords: blepharoplasty, congenital defect, eyelid, feline.

Sexual infantilism in a normal karotypic female related to ovarian agenesis associated with Mullerian agenesis – Case report

Purpose: To describe an unusual case of Mullerian agenesis associated with gonadal agenesis and thus sexual infantilism. Materials and Methods: Pelvic magnetic resonance imaging (MRI) and sonography were performed and MRI of the kidneys. Pelvic sonography and serum follicle stimulating hormone (FSH) were also obtained. Results: The only pelvic organ that this 15-year-old girl had was the distal portion of the vaginal canal. The kidneys were normal. Conclusions: This case suggests that at least in some cases some possible viral damaging process may lead to damage to both the ovaries and the Mullerian system. If there was a problem with the anti-Mullerian hormone (AMH), the kidney may be affected. Furthermore, AMH has nothing to do with the ovaries and a chance association of these two entities though possible, seems less likely than a common factor causing both problems.

46,XY disorder of sex development and developmental delay associated with a novel 9q33.3 microdeletion encompassing NR5A1

Steroidogenic factor 1 (SF1) is a nuclear receptor encoded by the NR5A1 gene. SF1 affects both sexual and adrenal development through the regulation of target gene expression. Genotypic male and female SF1 knockout mice have adrenal and gonadal agenesis with persistent Müllerian structures and early lethality. There have been several reports of NR5A1 mutations in individuals with 46,XY complete gonadal dysgenesis (CGD) or other disorders of sex development (DSD) with or without an adrenal phenotype. To date microdeletions involving NR5A1 have been reported in only two patients with DSDs.We report a novel microdeletion encompassing NR5A1 in a patient with 46,XY DSD and developmental delay. The phenotypically female patient initially presented with mild developmental delay and dysmorphisms. Chromosome analysis revealed a 46,XY karyotype. A 1.54 Mb microdeletion of chromosome 9q33.3 including NR5A1 was detected by array CGH and confirmed by FISH. Normal maternal FISH results indicated that this was most likely a de novo event. Since most NR5A1 mutations have been ascertained through gonadal or adrenal abnormalities, the additional findings of developmental delay and minor facial dysmorphisms are possibly related to haploinsufficiency of other genes within the 1.54 Mb deleted region. This report further confirms the role of NR5A1 deletions in 46,XY DSD and reinforces the utility of aCGH in the work up of DSDs of unclear etiology.