Challenges in the management of Turner syndrome with Y chromosome material: a case report of prophylactic gonadectomy revealing dysgerminoma.

Turner syndrome (TS) patients with Y chromosome material face an increased risk of gonadal germ cell tumors (GCTs). This case report discusses the challenges in decision-making regarding prophylactic gonadectomy, considering the risk of malignancy and the desire to preserve fertility. We report a case of a 12-year-old female with mosaic TS and Y chromosome material who initially presented with short stature and obesity. Karyotype analysis showed a mixed cell line (45X and 46XY). Counseling about the increased risk of developing GCT and preservation of gonadal function was provided, and we decided to delay gonadectomy until the age of 12. Prophylactic bilateral gonadectomy revealed dysgerminoma associated with GB at the age of 12. Fortunately, the patient was asymptomatic, with no additional therapy required due to the early stage of the disease. The case highlights the dilemma in managing TS patients with Y chromosome material, where the risk of GCT varies depending on the type of difference in sex development and gonadal function. The decision to delay gonadectomy reflects the emphasis on preservation of ovarian, although it poses a risk of malignancy. This case underscores the importance of individualized care in TS patients with Y chromosome material, balancing the risk of malignancy against preservation of ovarian. It emphasizes the need for timely and personalized decision-making in prophylactic gonadectomy.

A Risk of Gonadoblastoma in Familial Swyer Syndrome-A Case Report and Literature Review.

A complete gonadal dysgenesis (CGD) with 46,XY karyotype is known as the Swyer syndrome and belongs to the group of 46,XY differences of sex development (DSD). The main problem in patients with Swyer syndrome is the delayed puberty and primary amenorrhea. Moreover, intrabdominal dysgenetic gonads in the patient with genetic material of a Y chromosome may conduce to the development of gonadal tumors, such as gonadoblastoma or germinoma. The management of such patients is based on preventive excision of dysgenetic gonads and long-term hormonal replacement therapy. Sporadic cases are considered more common than familial cases. This paper presents two siblings with Swyer syndrome in whom gonadoblastoma was found. A thorough review of familial CGD with 46,XY DSD in the literature from the last 15 years suggests that the risk of gonadal tumors could be increased in familial compared to sporadic cases (66.6% vs. 15-45%, respectively).

WT1-related disorders: more than Denys-Drash syndrome.

Historically, specific mutations in WT1 gene have been associated with distinct syndromes based on phenotypic characteristics, including Denys-Drash syndrome (DDS), Frasier syndrome (FS), Meacham syndrome, and WAGR syndrome. DDS is classically defined by the triad of steroid-resistant nephrotic syndrome (SRNS) onset in the first year of life, disorders of sex development (DSD), and a predisposition to Wilms tumor (WT). Currently, a paradigm shift acknowledges a diverse spectrum of presentations beyond traditional syndromic definitions. Consequently, the concept of WT1-related disorders becomes more precise. A genotype-phenotype correlation has been established, emphasizing that the location and type of WT1 mutations significantly influence the clinical presentation, the condition severity, and the chronology of patient manifestations. Individuals presenting with persistent proteinuria, with or without nephrotic syndrome, and varying degrees of kidney dysfunction accompanied by genital malformations should prompt suspicion of WT1 mutations. Recent genetic advances enable a more accurate estimation of malignancy risk in these patients, facilitating a conservative nephron-sparing surgery (NSS) approach in select cases, with a focus on preserving residual kidney function and delaying nephrectomies. Other key management strategies include kidney transplantation and addressing DSD and gonadoblastoma. In summary, recent genetic insights underscore the imperative to implement individualized, integrated, and multidisciplinary management strategies for WT1-related disorders. This approach is pivotal in optimizing patient outcomes and addressing the complexities associated with these diverse clinical manifestations.

Elucidating the Cancer Phenotype in Turner Syndrome: A 20-Year Observational Cohort Study.

BACKGROUND/AIM: Turner syndrome confers increased cancer susceptibility; however, large-scale epidemiological evidence is lacking. This study aimed to analyze the incidence and prevalence of various malignancies in patients with Turner syndrome over 20 years of age to inform screening strategies. PATIENTS AND METHODS: We performed a retrospective cohort analysis of 11,502 patients with Turner syndrome from 2000 to 2020 utilizing the TriNetX research network database. The outcomes encompassed the incidence and prevalence of 20 cancers. Stratified analyses were used to evaluate variations in age, sex, and race. RESULTS: Key findings demonstrated markedly elevated risks of breast (1.7%), colon (1.0%), renal (0.4%), gonadoblastoma (0.4%), and other cancers. Significant demographic variations were observed in the incidence of cancers, such as gonadoblastoma, renal, and colon cancer. CONCLUSION: This large real-world study offers novel insights into the spectrum of cancer risk across adulthood in Turner syndrome. Our findings elucidate Turner syndrome's complex cancer phenotype to inform clinical decision-making, prognostication, and tailored screening strategies to ultimately advance patient care.

A rare case of Swyer syndrome from Pakistan in a young girl with primary amenorrhea and 46XY genotype.

Swyer syndrome is a condition where individuals with a 46XY karyotype, typically associated with males, display complete gonadal dysgenesis and lack testicular differentiation. This results from a mutation in the SRY gene, which is essential for testis development. As a consequence, affected individuals who appear phenotypically female have male chromosomes but do not develop functional testes. As a result, there is an absence of testosterone that leads to lack of masculinization and the presence of female genitalia. This article describes a 20-year-old female from Pakistan who exhibited primary amenorrhea. On examination, she possessed a typical female physique but lacked breast growth and axillary hair. She had scant pubic hair with female-type external genitalia. The pelvic imaging showed a underdeveloped uterus, along with small ovaries and fallopian tubes. Her karyotype came out to be 46XY. The examination and radiological results indicated Swyer syndrome. During laparoscopy, the patient's uterus was found to be infantile, while the fallopian tubes were healthy. Streak gonads were also present, and due to the risk of gonadoblastoma, they were surgically removed. Hormone replacement therapy was started to induce pubertal development and optimize bone mineral accumulation.

Gonadoblastoma in Turner syndrome with puberty delay: A case report and literature review.

BACKGROUND: Y chromosome material stands as an independent risk determinant for the onset of gonadoblastoma (GB) and subsequent gonadal germ cell tumours in individuals with Turner syndrome (TS). However, the delayed and underestimated identification of Y chromosome material through karyotyping within primary care settings exacerbates the intricacies of managing these patients over the long term. METHODS: We present a case involving TS accompanied by Y chromosome material, wherein puberty delay and GB were identified during prophylactic gonadectomy. Subsequently, we delve into the literature to explore the GB-related malignancy risk in TS patients with Y chromosome material, the incidence of Y chromosome presence in TS patients using methodologies beyond routine chromosomal testing, and the diagnosis and treatment of puberty delay in TS patients, all based on our case. RESULTS: A spectrum of more sensitive molecular techniques, including polymerase chain reaction (PCR) and fluorescence in situ hybridisation, effectively augments the detection of Y chromosome material alongside karyotyping. In addition to gonadectomy, the implementation of appropriate oestrogen therapy and a holistic, multidisciplinary approach to care can enhance the quality of life, while mitigating the long-term morbidity and mortality risks for TS patients harbouring Y chromosome material. CONCLUSIONS: Beyond gonadectomy, adopting a multifaceted approach the Y chromosome material detection, prompt initiation of puberty, tailored oestrogen therapy, and coordinated multidisciplinary management significantly contributes to the comprehensive health oversight of TS patients with Y chromosome material.

Frasier syndrome: A case report / El síndrome de Frasier, caso clínico

Introduction: Frasier syndrome is a genetic disorder produced by a mutation in intron 9 of the WT1 gene, responsible for renal and genital dysfunctions. Clinical findings: It is characterized by discrepancy between the individual karyotype and the individual phenotype and corticosteroid-resistant nephrotic syndrome due to focal segmental glomerulosclerosis. Patients usually have a female phenotype with a 46 XY karyotype, which increases the risk of gonadoblastoma in 50% of cases. Kidney disease requires kidney transplantation in adulthood. Cardiovascular and bone-derived comorbidities such as hyperlipidaemia and osteopenia/osteoporosis, respectively, are also common. Main diagnoses: Mutations of the WT1 gene can lead to different clinical entities, most notably Denysh-Drash syndrome, Frasier syndrome, or isolated focal segmental glomerulosclerosis. We present a clinical case of a woman who debuted in childhood with difficult-to-control nephrotic syndrome, the lack of pubertal development, primary amenorrhoea and the absence of ovaries on imaging tests in adolescence, alerted to an underlying genetic problem that, after cytogenetic studies, allowed a diagnosis of Frasier syndrome. Therapeutic interventions: It is recommended to remove the gonads due to increased risk of developing gonadoblastoma. Treatment of associated dyslipidaemia and osteopenia is also necessary. Conclusion: Frasier syndrome is an unusual cause of infertility due to gonadal dysgenesis and is associated with kidney problems.(AU)

Introducción: El síndrome de Frasier es un trastorno genético producido por una mutación en el intrón 9 del gen WT1, responsable de disfunciones a nivel renal y genital. Principales síntomas: Se caracteriza por disgenesia gonadal con discrepancia entre cariotipo-fenotipo y síndrome nefrótico resistente a corticoides debido a glomeruloesclerosis focal y segmentaria. Las pacientes presentan habitualmente fenotipo femenino con cariotipo 46 XY, lo que aumenta el riesgo de gonadoblastoma en un 50% de los casos. La enfermedad renal obliga a trasplante renal en la edad adulta. Son habituales también las comorbilidades derivadas a nivel cardiovascular y óseo como hiperlipidemia y osteopenia/osteoporosis, respectivamente. Diagnósticos principales: Las mutaciones del gen WT1 pueden conducir en distintas entidades clínicas entre las que destaca el síndrome de Denys-Drash, el síndrome de Frasier o la glomeruloesclerosis focal y segmentaria aislada. Se presenta un caso clínico de una mujer que debutó en la infancia con síndrome nefrótico de difícil control y que, durante la adolescencia, ante la falta de desarrollo puberal, la amenorrea primaria y la ausencia de ovarios en las pruebas de imagen alertaron de un problema genético subyacente que, tras estudios citogenéticos, permitió el diagnóstico de síndrome de Frasier. Intervenciones terapéuticas: Se recomienda la exéresis de las gónadas debido al riesgo incrementado de gonadoblastoma. El tratamiento de la dislipemia y la osteopenia asociadas también es necesario. Conclusión: El síndrome de Frasier es una causa inusual de infertilidad debido a una disgenesia gonadal y se asocia con problemas a nivel renal.(AU)

Yolk sac tumor and dysgerminoma in the left gonad following gonadoblastoma in the right gonad in a 46,XY DSD with a novel SRY missense mutation: a case report.

BACKGROUND: Approximately 10-15% of 46,XY disorders of sex development (DSDs) have an SRY mutation residing in the high mobility group (HMG) domain. Here, we present a case of 46,XY DSD caused by a novel missense mutation in the HMG region of SRY rapidly progressing to germ cell tumors (GCTs). CASE PRESENTATION: An adolescent female (15 years old) exhibiting primary amenorrhea was later diagnosed as a 46,XY female with bilateral gonadal dysplasia on the basis of peripheral lymphocyte karyotype 46,XY and a novel missense mutation in SRY (c.281 T > G, p.L94R). The novel missense mutation (c.281 T > G, p.L94R) and its adjacent region were conserved. Protein structure analysis showed that the mutant site was located in the middle of the HMG domain, and the mutant protein had a diminished ability to bind to DNA. Imaging examination revealed an adolescent female with a naive uterus. Laparoscopy and initial pathological examination revealed left gonadal dysplasia and right gonadal dysplasia with gonadoblastoma (GB). Right gonadectomy by laparoscopy was performed upon consent from the patient's parents. Less than 1 year postoperatively, the left gonadal gland deteriorated as observed by the findings of a mass in the left adnexal region by pelvic MRI and serum AFP > 1000 ng/ml by serological tests, and then total hysterectomy and adnexal and left gonadectomy by laparoscopy were performed. The GCT stage was classified as stage Ic according to FIGO. At this time, pathologic examination showed that the left gonad had progressed to yolk sac tumor and dysgerminoma. The patient underwent chemotherapy post-operatively but developed type III myelosuppression and tumor recurrence several months later. CONCLUSIONS: The patient initially presented with right gonadoblastoma but chose only right gonadectomy by laparoscopy to preserve the female sex characteristics, which resulted in rapid deterioration of the left gonad and poor treatment outcomes. This case demonstrates the importance of early genetic diagnosis and treatment of 46,XY female DSD.

WAGR, Sex Reversal, Bilateral Gonadoblastomas, and Intralobar Nephrogenic Rests: Uncertainties of Pre-Biopsy Chemotherapy in a High Risk Syndrome for Nephroblastoma.

Background: WT1 deletions are associated with nephroblastomas, WT mutations are associated with 46, XY sex reversal. It is unclear why only a few WT1 deletions are associated with sex reversal. Case report. This 46, XY female had a 15.2 MB interstitial deletion of 11p14.1p11.2, which included WT1 and FSHB. No pathogenic abnormalities were identified in 156 other genes associated with disorders of sexual development. Bilateral gonadoblastomas were incidentally diagnosed at 17 months of age at the time of prophylactic gonadectomies. She was treated without biopsy for bilateral nephroblastomas radiologically identified at 18 months of age. Bilateral partial nephrectomies contained treated intralobular nephrogenic rests. Conclusion: It is unclear why WT1 deletions are less associated with 46, XY sex reversal than WT1 mutations. Treating suspected nephroblastomas without biopsy, even in patients with syndromes associated with bilateral nephroblastomas, may still lead to diagnostic and therapeutic uncertainties.

The emerging role of NF2 alterations in new and established subtypes of renal cell carcinoma.

Genomic alterations are increasingly important in the current paradigms for the classification, diagnosis, and treatment of renal cell carcinoma. Biallelic alterations involving NF2 have been identified across several currently recognized subtypes of renal cell carcinoma including clear cell renal cell carcinoma and papillary renal cell carcinoma among others and may be associated with a more aggressive disease course as well as advanced stage at presentation. In addition, emerging evidence suggests the existence of a clinicopathologically distinct subset of renal cell carcinoma cases driven by biallelic loss of NF2 expression. This subset of tumors is morphologically characterized by a constellation of morphologic features including hyalinizing fibrosis, eosinophilic cytology, psammomatous calcifications, and a nested growth pattern. These tumors include the recently described entities of biphasic hyalinizing psammomatous renal cell carcinoma as well as renal cell tumor with sex cord/gonadoblastoma-like features. Despite their oftentimes aggressive behavior, there is some evidence that these tumors may respond favorably to treatment regimens incorporating immune checkpoint inhibitors.

[Gonadoblastoma: Clinicopathological study and literature review of 3 cases].

OBJECTIVE: To investigate the clinical feature, pathological morphology, special histopathological subtype and immunohistochemical characteristic of gonadoblastoma. METHODS: Three patients of gonadoblastoma treated from 2014 to 2020 were enrolled, and the clinical characteristics, histological morphology and immunophenotype were analyzed, and the literatures were also reviewed. RESULT: Three phenotypical females were 14,17 and 27 years old. Case 1 was 46,XX with normal gonadal development. Case 2 was 46,XY and case 3 was chromosomal chimeric type (46, XY 90%/45,X 10%), both with dysgenetic gonads. Microscopically, the morphology of classic type was observed in all cases more or less, manifesting small nests of primitive germ cells and surrounding clustered sex cord-like cells, usually with Call-Exner like bodies and calcification. In additon, the morphology of special subtype can be seen in case 1,exhibiting cord-like tumor cells, which was segmentated by cellular fibrous stroma. Cases 2 and 3 were accompanied by dysgerminoma components. Immunohistochemically,all the primal germ cells were positive for OCT3/4, PLAP and CDll7 , and sexcord-like cells were positive for inhibin, SF-1, SOX9 and FOXL2 . Patients were followed up for 10 years, 6 years and 4 years respectively without recurrence. CONCLUSION: Gonadoblastoma is a rare germ cell-sex cord stromal tumor, which is usually accompanied by gonadal hypoplasia. As a special subtype, dissecting gonadoblastoma will be easily confused with dysgerminoma/seminoma, but the prognosis is better. So we should improve the understanding of this subtype and avoid overdiagnosis.

Gonadoblastoma in a patient with 45,X/46XY mosaicism.

45,X/46,XY mosaicism is a sex development disorder with an estimated incidence of less than 1 in 15,000 live births. Various studies have shown there is an increased risk of germ cell tumours forming in Mosaic Turner syndrome. This includes gonadoblastoma, a clinically benign mixed germ-stromal cell tumour. However, this can later develop into one or several malignant germ cell neoplasms, for which early prophylactic gonadectomy is often recommended in patients with 45,X/46,XY mosaicism. The study presents the case of an 11-year-old patient diagnosed with a Mosaic Turner syndrome karyotype, who underwent prophylactic bilateral gonadectomy.

Gonadal Y-chromosome mosaicism with 45, X Turner syndrome complicated with bilateral HCG-secreting gonadoblastoma.

We report a rare case of bilateral HCG-secreting gonadoblastomas (Gb) in a 5.25-year-old girl of 45, X Turner syndrome (TS) with gonadal Y chromosome mosaicism. The clinical data were summarized, and the literatures were reviewed. The patient had enlarged breasts for 2 years and 3 months, with elevated ß-HCG of blood found for 8 months. The level of ß-HCG of cerebrospinal fluid, cranial MRI, chest and abdominal CT, and pelvic MRI were normal. After surgical gonad exploration, biopsy and excision, gonad venous blood hormone examination and SRY gene detection of gonad tissue, the diagnosis was confirmed as HCG-secreting Gb (bilateral) and TS (45, X) with gonad Y chromosome mosaicism. The patient received 4 courses of chemotherapy, and regular outpatient follow-up. At 9 months after gonadectomy, there was no clinical, laboratory, or radiological evidence of recurrence. We reported a nonclassical case of 45, X Turner syndrome (TS) with gonadal Y chromosome mosaicism, who presented with breast development as the first manifestation and then virilization due to bilateral HCG-secreting gonadoblastomas. Detection of serum ß-HCG and AFP is requisite for the diagnosis of precocious puberty, karyotyping is important for virilizing phenotypic female, and virilization in Turner syndrome implies the existence of Y chromosome(substance) (peripheral blood or tissue mosaicism) and the occurrence of gonadal tumors.

Characteristics and karyotype analysis of a patient with turner syndrome complicated with multiple-site tumors: A case report.

Turner syndrome (TS) is a congenital chromosomal abnormality that affects approximately 1 in 2,500 people. Both in China and abroad, few studies exist on the incidence of tumors in patients with TS. Most reported cases are complicated with gonadal germ cell tumors, and extragonadal tumors are rare, with the latter not yet being reported in China. Through chromosome karyotype analysis and surgical exploration, a pediatric patent was diagnosed with TS complicated with gonadoblastoma and adrenal neuroblastoma. The patient was short in stature and had a facial deformity. After admission, adrenal computed tomography was conducted, and a right adrenal mass was identified as a neurogenic tumor. After surgical resection and gonadal exploration, the pathological results revealed left gonadoblastoma, right gonadal stromal cell hyperplasia, and ganglion neuroblastoma (mixed type) in the right adrenal gland. Pediatric patients with TS have an increased likelihood of developing neuroblastoma and adrenal-related tumors, and changes in adrenal hormone levels and clinical manifestations are often not obvious when combined with adrenal-related tumors. To avoid missed diagnosis and delayed treatment, screening for adrenal tumors is therefore recommended for patients with TS before the initiation of growth hormone treatment.

Consensus guide on prophylactic gonadectomy in different sex development.

The risk of suffering from gonadal germ cell tumors (GCT) is increased in some patients with different sexual development (DSD), mainly in those with Y chromosome material. This risk, however, varies considerably depending on a multitude of factors that make the decision for prophylactic gonadectomy extremely difficult. In order to make informed recommendations on the convenience of this procedure in cases where there is potential for malignancy, this consensus guide evaluates the latest clinical evidence, which is generally low, and updates the existing knowledge in this field.

The Mysteries of Primary Amenorrhea: Swyer Syndrome.

Swyer syndrome is a hereditary condition seen in a few patients who present with primary amenorrhea, characterized by 46 XY and the presence of female internal genital tract and bilateral streak gonads in a female phenotype. A 25-year-old lady presented with primary amenorrhea. After the evaluation, she was diagnosed with Swyer syndrome due to a mutation in the SRY gene, leading to failure of testicular development. The clinical presentation was that of a female phenotype with no secondary sexual characteristics. On physical examination, she had a female phenotype with a short vagina and no secondary sexual characteristics. The MRI revealed a hypoplastic uterus with both fallopian tubes but with streak gonads. The patient's genotype was found to be 46 XY after genetic testing. The streak gonads were removed laparoscopically due to the future risk of gonadoblastoma, and the patient was given hormone replacement therapy (HRT). The patient started menstruating after six months of HRT and has been developing secondary sexual characteristics (Tanner stage II) till now.

A rare case of ovarian gonadoblastoma flourishing into malignant mixed germ cell tumour with review of literature.

Gonadoblastoma is an extremely rare neoplasm of the ovary showing admixture of germ cells and sex cord cells. It may be associated with gonadal dysgenesis. Gonadoblastoma cells may give rise to individual germ cell tumours or mixed germ cell tumours with variable tumour components. Very few cases of ovarian gonadoblastoma admixed with malignant germ cell tumours have been recorded worldwide. Because of the rareness of the tumour, a component of gonadoblastoma might be overlooked on microscopic examination. Here we report a rare case of ovarian gonadoblastoma giving rise to an admixture of immature teratoma and dysgerminoma. We discuss microscopic features, immunohistochemistry findings and review of literature.

Dissecting Gonadoblastoma of the Ovary Coexistent with an Atypical Endometriotic Cyst: Incidental Detection in Cystectomy Specimen of a Woman with 46,XX Karyotype.

Dissecting gonadoblastoma (DGB) of the ovary, a recently described terminology, defines a unique distribution of neoplastic germ cells. Here, we report a case of incidental DGB coexistent with an atypical endometriotic cyst occurring in a 23-year-old woman. The ovarian cyst was lined by endometrial-like glands and stroma. Some glands displayed nuclear enlargement and hyperchromasia, and abundant eosinophilic cytoplasm with occasional intracytoplasmic hemosiderin and mucin vacuoles. The neoplastic germ cells resembled those of ovarian dysgerminoma and were diffusely distributed within the ovarian stroma, which was stretched around the wall of the endometriotic cyst. These cells were arranged in nests and cords, possessing clear cytoplasm and centrally located round nuclei with prominent nucleoli and occasional mitoses. Chromosomal analysis revealed a 46,XX karyotype. We describe the clinical, histological, immunophenotypical, and genetic features of ovarian DGB incidentally detected in the ovarian cystectomy specimen of a woman with normal female karyotype.

Adnexal Torsion Due to Borderline Mucinous Tumor of the Gonad in a Prepubertal Girl with Mixed Gonadal Dysgenesis (45,X/46,XY) and a Turner Phenotype.

BACKGROUND: Turner syndrome (TS) is a sex chromosome condition characterized by complete or partial loss of the X chromosome. Patients with mixed gonadal dysgenesis (45,X/46,XY) and a Turner phenotype are predisposed to gonadoblastoma with malignant transformation. CASE: We present the case of a TS patient with 45,X/46,XY with 2 episodes of left adnexal torsion (AT). Biopsies during detorsion showed benign mucinous cystadenoma. Pathology following bilateral gonadectomy revealed a left gonad with mucinous borderline tumor and right gonad with gonadoblastoma, both of which have malignant potential. SUMMARY AND CONCLUSION: Gonadectomy is recommended in XY gonadal dysgenesis to decrease risk of malignant transformation from gonadoblastoma. Although rare in pediatric patients, ovarian malignancies have been identified among AT cases. To our knowledge, we present the first case of AT due to borderline ovarian mucinous tumor of the ovary and contralateral gonadoblastoma in a patient with mixed gonadal dysgenesis (45,X/46,XY) and a Turner phenotype.

Early Bilateral Gonadoblastoma in a Patient with Mixed Gonadal Dysgenesis (Karyotype 45,X/46,XY): Case Report and Review of Literature.

Background: Mixed gonadal dysgenesis is a rare congenital and challenging condition, characterized mainly by 45,X/46,XY karyotype mosaicism, asymmetrical gonadal development and various internal and external genital anatomy. Because of frequent disorder of genital development and a higher risk of germ cell neoplasia, management of these patients is complex and requires multidisciplinary approach. Case: We present a 45,X/46,XY mixed gonadal dysgenesis patient diagnosed with gonadoblastoma in both gonads after bilateral gonadectomy at 1 year of age. Conclusions: Because of high risk for malignant transformation, gonadectomy of a streak-like gonad and biopsy with orchidopexy or gonadectomy of a dysgenetic testicle is recommended at an early age.