Testicular regression syndrome (TRS) is a cause of nonpalpable testis resulting from prenatal testicular involution. This study aims to describe clinical, ultrasonographic, and laparoscopic characteristics and surgical management of TRS, and to evaluate the necessity of inguinal exploration following laparoscopy. A retrospective descriptive study was conducted on boys <16 years who underwent laparoscopic exploration for unilateral intra-abdominal nonpalpable testes at Vietnam National Children's Hospital between January 2021 and October 2025 and were diagnosed intraoperatively with TRS. Data collected included age, laterality, ultrasonographic findings, laparoscopic features, the decision to perform inguinal exploration, and histopathology of nubbin. Contralateral testicular size was measured by ultrasonography and compared with age-matched normal values, with p < 0.05 considered statistically significant. Forty-three patients were included; median age at surgery was 26 months (range 9-156 months), and 32 cases (74.4%) involved the left side. Ultrasonography yielded false-positive findings in 12 cases (27.9%). Contralateral testicular volume was larger than normal in children <24 months (0.86 ± 0.23 vs. 0.44 ± 0.14 mL; p < 0.001) and 24-60 months (0.90 ± 0.44 vs. 0.57 ± 0.16 mL; p = 0.025), but not in those >60 months (p = 0.263). Spermatic vessels and vas deferens terminated proximal to the ring in 3 cases (7.0%) and traversed the ring in 40 cases (93.0%). Inguinal exploration was performed in 17/43 patients (39.5%), revealing and excising 13 testicular remnants (30.2%). Specimens sent for histopathology showed no testicular or seminiferous tissue. Testicular regression syndrome (TRS) is characterized by left-sided predominance and age-dependent compensatory hypertrophy of the contralateral testis. Ultrasonography is unreliable for diagnosis. While inguinal exploration frequently identifies fibrous remnants containing histological markers of regression, the clinical necessity of routine excision remains debated. We advocate for an individualized management approach that balances the benefits of definitive diagnosis against the low risk of malignancy.

We report two cases of 46,XY siblings with pontocerebellar hypoplasia type 7 (PCH7) and conduct a systematic literature review for genetically confirmed PCH7 cases, focusing on phenotypic characteristics, particularly gonadal parameters, and associated genotypic data. Two 46,XY siblings diagnosed with PCH7 were reviewed. Both exhibited hypoplastic male external genitalia, absent uterus, and cryptorchid testes, confirmed through histological assessments showing dysgenesis. A systematic literature search revealed an additional 26 cases of 46,XY PCH7, with neurological involvement noted in all cases except one. The external genitalia were described as abnormal (17/23); however, few of these were hypoplastic male type on pictorial review. Nonlocalized testes (5/5) and absent uterus (4/7) on ultrasonography, elevated FSH (7/7), and low testosterone (3/3) were observed. Besides a novel variant (p.Ile133Thr) in Indian siblings, a total of 25 variants in TOE1 were identified with no specific genotype-phenotype correlation. Testicular development was defective in all PCH7 patients but was variable, with the predominant phenotypic manifestation being testicular regression syndrome/partial gonadal dysgenesis with Müllerian duct regression (TRS/PGD-MDR).

Testicular Regression Syndrome (TRS) represents a form of cryptorchidism characterised by the absence of testicular tissue with persistence of cord structures. While excision of remnants is routinely advocated due to potential malignant risk from seminiferous tubules (SNTs) or germ cells (GCs), the actual risk remains debated, and no universal consensus exists. We conducted a retrospective review of 262 children with clinically impalpable testes who underwent diagnostic laparoscopy and/or inguinal exploration at a single tertiary centre between 2008 and 2022. Testicular remnants excised were subjected to detailed histopathological examination for seminiferous tubules (SNTs), germ cells (GCs), and features of regression. The median age at surgery was three years, and 83 % of remnants were left-sided. Intra-abdominal remnants were identified in 5 % of patients. Histology demonstrated vas deferens in 86 % and epididymal tissue in 66 % of specimens. SNTs were identified in 10.3 % of cases, while viable GCs were present in only 1.1 %. Calcifications and hemosiderin deposits were seen in 29 %. Intra-abdominal remnants showed significantly higher incidence of SNTs/GCs (62 %) compared to inguinal (10 %) or scrotal (4 %) sites (p < 0.0001). TRS remnants rarely harbour viable GCs, and no invasive malignancy has been reported. Excision is recommended for intra-abdominal remnants, whereas selective management of inguino-scrotal remnants may be appropriate. Larger prospective studies are needed to establish evidence-based guidelines for TRS management.

RNF113A-related disorders are rare X-linked conditions characterized by neurodevelopmental impairment, endocrine abnormalities, and gonadal dysgenesis. To date, this condition has been documented in only a few individuals. We report 46,XY twin siblings with a hemizygous pathogenic RNF113A variant [c.901C > T, p.(Gln301*)], presenting with a remarkably consistent phenotype that includes microcephaly, corpus callosum dysgenesis, intractable epilepsy, subclinical hypothyroidism, microphallus, and bilateral testicular regression syndrome (TRS). Whole-exome sequencing identified a maternally inherited variant consistent with X-linked recessive inheritance. Despite the absence of testicular tissue, both twins had evidence of prenatal androgen exposure. Thyroid dysfunction evolved during infancy. These cases expand the phenotypic spectrum associated with pathogenic RNF113A variant and provide evidence linking this gene to TRS. They further highlight the importance of whole-exome sequencing in evaluating complex 46,XY disorders of sex development with multisystem involvement. RNF113A should be considered in the genetic evaluation of 46,XY disorder of sex development and TRS, particularly when accompanied with multisystem involvement.

<p>Introduction: SEMA3E is a secreted class 3 semaphorin that, in mice, plays roles in neuronal guidance, cardiovascular morphogenesis, angiogenesis, and vascular homeostasis. Adult male mice lacking SEMA3E exhibit reduced testicular size compared to wild-type littermates, indicating a potential role in reproductive function. In humans, heterozygous missense variants in SEMA3E were initially reported to be associated with CHARGE syndrome and hypogonadotropic hypogonadism with anosmia. However, these associations have since been questioned, and the contribution of SEMA3E variants to human disease is unclear. We describe the results of exome sequencing of a 46,XY boy with unexplained bilateral testicular regression syndrome and optic nerve atrophy. Exome sequencing indicates that he carries a heterozygous frameshift variant (c.942del, p.Leu314PheTer11) in the SEMA3E gene. The variant is located within the functional SEMA domain of the protein and is predicted to trigger nonsense-mediated mRNA decay. This is the second reported loss-of-function (LoF) variant in the highly conserved SEMA3E gene. A previously described LoF variant was identified in a child presenting with severe intellectual disability and cognitive regression. LoF SEMA3E variants may be associated with a broad and variable spectrum of clinical phenotypes. </p>.