OBJECTIVE: To summarize the clinical and genetic characteristics of a child with 46,XX Ovotesticular disorder of sex development (46,XX OTDSD) due to copy number variation of SOX3 gene. METHODS: A 46,XX male patient presented at the Capital Center for Children's Health, Capital Medical University in November 2024 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were taken from the child and his parents and subjected to trio whole-genome sequencing. Skewed X-chromosome inactivation was tested in the child and his mother. A literature review was carried out on 46,XX males associated with mutations of the SOX3 gene. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: SHERLL2025056). RESULTS: The 10-year-old boy presented with hypospadias and cryptorchidism at birth. Chromosome analysis at one year and a half revealed a 46,XX karyotype. Gonadal biopsy showed testicular tissue, while ultrasound at the age of 10 detected ovotesticular tissue. Whole-genome sequencing identified a 660 kb duplication in the Xq27.1 region, which was derived from his mother. X-chromosome inactivation testing showed random inactivation in the child and mild non-random inactivation in the mother. Literature review has found 11 publications involving 15 patients (including our case), among whom 14 had a male social gender. They had primarily presented with hypospadias at birth but had no significant endocrine abnormalities. Most patients had experienced testicular failure after puberty. SOX3 related 46,XX males are mainly caused by de novo duplications, although a few maternal carriers had been discovered. CONCLUSION Duplication of the SOX3 gene probably underlay the pathogenesis is this 46,XX male. Individuals with 46,XX SRY negative male phenotypes should be routinely screened for SOX3 gene variants. Structural variations of the SOX3 gene can lead to complete or partial sex reversal in 46,XX individuals with minimal impact on intellectual and motor development, as well as other endocrine hormones.
Child ; Humans ; Male ; 46, XX Disorders of Sex Development/genetics* ; DNA Copy Number Variations ; Gene Duplication ; Phenotype ; SOXB1 Transcription Factors/genetics*

OBJECTIVE: To investigate the detection patterns, clinical phenotypic characteristics, and differences in diagnostic timeliness of Klinefelter syndrome (KS) across prenatal and postnatal stages, with an aim to provide a basis for optimizing strategies for early screening, diagnosis, and intervention. METHODS: A retrospective study was conducted to analyze data from two phases. The prenatal diagnosis group included 33,302 pregnant women who underwent amniocytic karyotyping due to advanced maternal age, abnormal ultrasound findings, or high-risk non-invasive prenatal testing (NIPT). The postnatal diagnosis group included 52,101 patients who underwent peripheral blood karyotyping due to primary infertility, abnormal external genitalia, or growth and developmental abnormalities. Additionally, medical histories of adult diagnosed patients were reviewed retrospectively to identify early occult symptoms. This study was approved by the Medical Ethics Committee of Chengdu Women's and Children's Central Hospital (Ethics No.: LCYJ-2025-030). RESULTS: In the prenatal group, 96 cases of KS were detected (detection rate 0.29%). The primary indications for referral were NIPT indicating sex chromosome abnormalities (45.83%), advanced maternal age (16.66%), and ultrasound abnormalities (17.70%). In the postnatal group, 128 cases of KS were detected (detection rate 0.25%). Clinical presentations were primarily primary infertility/azoospermia (77.34%), and the patients were predominantly adults (84.40%). Retrospective analysis revealed that adult patients presented with specific physical signs that had been overlooked during childhood. CONCLUSION As KS lacks typical early clinical manifestations, diagnosis is often delayed until adulthood when reproductive needs arise, showing a pattern of "passive detection" and resulting in missed opportunities for optimal intervention. By conducting a comparative analysis of prenatal diagnostic data and postnatal retrospective data, a risk association model linking prenatal screening indications with childhood-specific signs was developed. This study has provided empirical evidence for establishing a multidisciplinary, full life-cycle management system of "screening ~ diagnosis ~ monitoring ~ intervention" helping to shift from "passive detection in adulthood" to "proactive management across the entire life course," and laid a foundation for improving early diagnosis rate and long-term quality of life for patients.
Humans ; Klinefelter Syndrome/genetics* ; Female ; Adult ; Pregnancy ; Retrospective Studies ; Prenatal Diagnosis/methods* ; Male ; Phenotype ; Karyotyping ; Young Adult ; Adolescent ; Middle Aged

Introduction: Swyer syndrome (46, XY gonadal dysgenesis) is a rare disorder of sex development, characterized by a phenotypic female with streak gonads and hypergonadotropic hypogonadism. It presents with primary amenorrhea and delayed puberty. Overlapping clinical features with Turner syndrome may cause diagnostic uncertainty, highlighting the role of karyotypic evaluation in diagnosis. Case: A 35-year-old phenotypic female was first evaluated at age 27 during admission for an acute viral illness, when incidental findings of primary amenorrhea, short stature (height 131 cm), webbed neck, pectus excavatum, and absent secondary sexual characteristics raised suspicion of Turner syndrome. She had hypertension, with initial imaging suggesting coarctation of the thoracic aorta. CT angiography showed focal narrowing of the descending aorta; multidisciplinary review favored aortic folding, and she was managed conservatively. Endocrine evaluation demonstrated hypergonadotropic hypogonadism, with markedly elevated follicle-stimulating hormone (FSH 108.6 IU/L) and luteinizing hormone (LH 23.16 IU/L) in the presence of low estradiol levels. Pelvic imaging revealed an atrophic uterus with absence of bilateral ovaries, consistent with gonadal dysgenesis. Karyotypic analysis was performed, demonstrating a 46, XY genotype with confirmed SRY gene presence, establishing the diagnosis of Swyer syndrome. DEXA scan demonstrated osteoporosis, in keeping with prolonged hypogonadism. She was commenced on hormone replacement therapy, resulting in the development of secondary sexual characteristics and regular withdrawal bleeding. She remains under structured multidisciplinary follow-up, with endocrine-led management of hypothyroidism and osteoporosis, alongside cardiology follow-up and gynecological surveillance. Conclusion This case highlights the diagnostic complexity of disorders of sex development with overlapping phenotypes and the need for re-evaluation when clinical progression is atypical. Diagnosis enables hormone replacement therapy for induction of secondary sexual characteristics and preservation of bone health. Integration of clinical, biochemical, and genetic data within a multidisciplinary framework is essential to achieve diagnostic accuracy and optimize outcomes.
Turner Syndrome

Introduction: Steroid cell tumors are rare sex cord-stromal tumors, accounting for <0.1% of ovarian neoplasms. Extraovarian steroid cell tumors are exceptionally rare, often androgensecreting, and pose significant diagnostic challenges. Early recognition is essential to prevent prolonged morbidity from hyperandrogenism. Case: A 60-year-old female, 15 years after total hysterectomy and bilateral salpingo-oophorectomy for a large ovarian mass with massive ascites, presented with deranged liver function tests on routine follow-up. Ultrasonography and computed tomography imaging revealed multiple hypervascular lesions in the liver, retroperitoneum, and peritoneum, suggestive of metastatic disease, with normal-appearing adrenal glands. Biopsy of a liver lesion demonstrated a metastatic neoplasm with morphology and immunoprofile favoring a steroid cell tumor. However, metastasis from the adrenal cortex or an ovarian primary could not be excluded. Given the prior bilateral oophorectomy, metastatic adrenocortical carcinoma was initially suspected, prompting endocrine evaluation. Further history revealed a 1-year history of progressive virilization, including increased facial hair and frontal balding. Hormonal studies demonstrated elevated testosterone (12.2 mmol/L and reference range 0.1–1.42) and dehydroepiandrosterone sulfate (15.9 µmol/L and reference range 0.510–5.560) and the adrenocorticotropic hormone level of 11.7 pmol/L (reference range 1.60–13.9) with suppressed gonadotrophins. Additional workup for catecholamine, cortisol, and aldosterone excess was unremarkable. The discordance between androgen excess and normal adrenal imaging, despite absent ovarian tissue, suggested an extraadrenal androgen-secreting steroid cell tumor. A second histopathology review and multidisciplinary discussion with radiology, gynecologic oncology, and pathology teams were undertaken. As the disease was deemed inoperable, repeat retroperitoneal lesion biopsy confirmed metastatic steroid cell tumor and guided palliative chemotherapy. She was subsequently referred to gynecologic oncology for systemic chemotherapy. Conclusion Extra-adrenal steroid cell tumors, though rare, should be considered in patients with hyperandrogenism long after bilateral oophorectomy, especially when adrenal imaging is normal. Multidisciplinary evaluation and repeat biopsy are often crucial for establishing the diagnosis and guiding treatment.
Hyperandrogenism ; Ovariectomy ; Steroids ; Neoplasms

Introduction: Polycystic ovary syndrome (PCOS) is the most common cause of hyperandrogenism in women of reproductive age. However, several endocrine disorders, particularly Cushing disease (CD), can closely mimic the clinical, biochemical, and radiological features of PCOS. This overlap may lead to misdiagnosis and delayed recognition of hypercortisolism, with significant metabolic and reproductive consequences. Case: We report a 24-year-old female with young-onset diabetes mellitus who was referred for endocrine co-management during admission for recurrent mons pubis and labial abscesses with poorly controlled glycemia. She had a 5-year history of progressive hirsutism, oligomenorrhoea, scalp hair loss, significant weight gain, and insulin resistance, and had previously been labelled as having PCOS during adolescence, with subsequent default of follow-up. On examination, she was obese (body mass index 33 kg/ m²) with plethoric facies, acanthosis nigricans, proximal myopathy, and hirsutism (Ferriman–Gallwey score 10), without overt virilization or acromegalic features. Biochemical evaluation demonstrated severe hyperandrogenism with markedly elevated total testosterone (7.05 nmol/L), suppressed gonadotropins, and adrenocorticotropic hormone (ACTH)-dependent hypercortisolism. Cortisol failed to suppress on low-dose dexamethasone testing, and 24-hour urinary free cortisol was markedly elevated (>4,900 nmol/24 h). Pelvic ultrasonography and computed tomography imaging showed polycystic ovarian morphology without evidence of an ovarian mass. Pituitary magnetic resonance imaging revealed a small right-sided pituitary microadenoma measuring 2.6 × 3.7 mm. Inferior petrosal sinus sampling demonstrated a central-to-peripheral ACTH gradient with adequate prolactin ratios, confirming pituitary CD. Conclusion This case highlights how Cushing disease can closely mimic PCOS, including polycystic ovarian morphology and hyperandrogenism. Progressive symptoms, severe biochemical androgen excess, and marked insulin resistance should prompt evaluation for secondary causes of hyperandrogenism, particularly hypercortisolism, to avoid delayed diagnosis and prolonged morbidity.
Female ; Hyperandrogenism ; Pituitary ACTH Hypersecretion ; Polycystic Ovary Syndrome

Introduction: Short stature and delayed puberty characterize Turner syndrome (TS). The 2024 international clinical practice guidelines recommend growth hormone (GH) for latediagnosed patients if epiphyses remain open. For patients with remaining growth potential, initiating GH alongside low-dose estrogen effectively balances linear growth with the need for timely pubertal induction. Case: A 15-year-old female, born prematurely at 6 months gestation, presented with delayed puberty, primary amenorrhea, and short stature. Examination revealed a height of 122 cm (<5th percentile), weight of 26 kg, with no syndromic facies, and Tanner stage 1. Investigations confirmed hypergonadotropic hypogonadism. Metabolic screening, including thyroid, renal, and liver profile, was normal. Her baseline insulin-like growth factor 1 (IGF-1) was low at 117.5 ng/mL (127.5–541.5). Karyotyping confirmed mosaic TS (45,X/46,Xr). Her skeletal bone age was delayed at 12 years, indicating a viable window for linear growth prior to complete epiphyseal fusion. Subcutaneous GH was initiated at 0.3 mg up titrated to 1.2 mg (0.45 µg/kg) daily over 4 weeks, then 1.35 mg (50 µg/kg) daily at month 5. Low-dose oral estradiol (0.5 mg three times weekly) was introduced for pubertal induction at month 4. After 9 months of combined GH and estrogen therapy, the patient achieved a height increment of 6 cm, reaching 128 cm without an adverse event. To achieve the clinical target of a 10–15 cm increment in the first year, her GH dose was further increased to 1.50 mg (55 µg/kg) daily. She showed an appropriate biochemical response with IGF-1 increased to 40.2 nmol/L (16.4–67.8) with a total height gain of 6 cm over the first 9 months of GH therapy. Conclusion Concomitant GH and estrogen therapy in late-diagnosed TS successfully induced clinically significant height gain. This dual approach maximized the limited window for linear growth, without delaying pubertal induction and compromising patient’s psychosocial well-being.
Turner Syndrome

Introduction: Partial androgen insensitivity syndrome is a rare X-linked 46, XY disorder caused by androgen receptor dysfunction, producing variable genital ambiguity and complex diagnostic challenges in early infancy and childhood. Case: We report a term infant, currently aged 9 months, who was admitted to the Neonatal Intensive Care Unit at birth for glucose-6-phosphate dehydrogenase (G6PD) deficiency and noted to have ambiguous genitalia. The infant had no hypoglycemia, feeding intolerance, or electrolyte disturbances throughout admission. She is the second child of non-consanguineous parents, with no family history of disorders of sex development. Examination of the external genitalia revealed a prominent phallus without erectile tissue with mildly pigmented and rugated labioscrotal folds. There was no labioscrotal fusion. Bilateral gonads were palpable in both labioscrotal folds with one opening seen. Pelvic ultrasonography showed bilateral small testes within the labioscrotal folds, with absence of Müllerian structures. Karyotype analysis confirmed 46, XY genotype. Human chorionic gonadotropin stimulation (HCG) testing at day 7 of life demonstrated normal baseline testosterone 4.9 nmol/L, but minimal testosterone rise 5.4 nmol/L at day 4 post HCG. Normal testosterone to dihydrotestosterone ratio and testosterone to androstenedione ratio excluded defects in androgen synthesis, while normal adrenal steroid profile ruled out congenital adrenal hyperplasia. Gonadotropin-releasing hormone stimulation at 2 months old revealed a peak follicle-stimulating hormone of 8 IU/L and peak LH of 4 IU/L. Anti-Müllerian hormone level was markedly elevated >328 pmol/L (normal 5.5–103 pmol/L). Whole-exome sequencing identified a hemizygous androgen receptor gene variant, p.(Pro818Ala), classified as a variant of uncertain significance with deleterious in silico predictions, consistent with X-linked partial androgen insensitivity syndrome. Conclusion This case highlights the necessity of early, systematic endocrine evaluation integrated with genomic testing in 46, XY DSD to achieve a definitive diagnosis, optimize sex assignment, and guide longitudinal, multidisciplinary management.
Male ; Infant ; Androgen-Insensitivity Syndrome

BACKGROUND

Polycystic ovarian syndrome (PCOS) is a common gynecologic endocrine disorder affecting between 2.2% and 26% of the population. It is typically characterized by hirsutism and signs of ovulatory dysfunction. Hirsutism is defined as the presence of excess body or facial terminal hair growth in females, following a male-like pattern. It is diagnosed using visual assessment methods, such as the modified Ferriman–Gallwey (mFG) scoring system, and biochemical tests, including measurements of total testosterone (tT) and the free androgen index (FAI).

The general objective of the study is to identify the correlation of visual scoring with the biochemical evaluation of hirsutism. Specific objectives include (1) to describe the visual and biochemical scores of hirsutism in PCOS patients and (2) to determine a cutoff score for the visual scoring of hirsutism among Filipinos.

This is a cross-sectional study done in a tertiary hospital. Ethical approval was obtained for this study. Patients who satisfied the inclusion criteria were included in the study. Age, height, weight, body mass index (BMI), and OB score were noted. Visual scoring for hirsutism using the mFG scoring system was performed. Blood extraction was done for testosterone and sex hormone-binding globulin tests. FAI was then computed and correlated with the mFG scores.

A total of 52 patients were identified. A positive correlation is noted between the mFG with testosterone and FAI. A positive correlation was also noted between the BMI with testosterone and FAI. An mFG value of >4 is an acceptable cutoff for Filipinos.

The study showed as the mFG score increases, FAI and tT levels also increase. It was also noted that as BMI increases, the FAI and tT levels are also expected to increase. It can also be concluded that a lower mFG cutoff value, >4, is applicable for Filipinos.

BACKGROUND

Turner syndrome (TS) is the most common sex chromosomal abnormality in females resulting from a missing X chromosomal material. This in turn results in a range of clinical manifestations. This study aimed to provide the data on the cases of TS confirmed via chromosomal analysis in a cytogenetics laboratory in the Philippines as well as the role of genetic counseling.

A review of the karyotyping results of the Cytogenetics Laboratory, Institute of Human Genetics, National Institutes of Health, University of the Philippine Manila from 1991 to 2020.

TS accounted for 2.64% of all the samples received from 1991 to 2020. For 30 years, the most common karyotype in TS was the classical TS or the standard monosomy 45, X noted in 195 patients or 37.69% of all patients diagnosed with TS. Mosaicism with a normal female karyotype was noted in 50 patients (9.62%). For the TS variants, the most common is isochromosome Xq seen in 125 patients (24.04%). This is followed by TS with marker chromosome in 55 patients (10.58%) and ring X chromosome in 23 patients (4.42%). Deletion Xp and deletion Xq were noted in 22 patients (4.23%) and 20 patients (3.85%), respectively.

From this study, it can be noted that chromosomal analysis or standard karyotyping is a vital and useful diagnostic tool in TS. The information obtained from it may be useful in clinical decision-making of families and healthcare providers. Its importance in providing adequate genetic counseling cannot be overemphasized.

This report details the case of a 24-year-old Filipino individual born with ambiguous genitalia, assigned female at birth, and raised as such. Around the age of 13, the patient began to develop secondary male characteristics. Medical assessment was postponed until the onset of abdominal pain led the patient to seek consultation. Cytogenetic testing revealed a sex chromosome disorder of sexual development with a mosaic karyotype of 45,X/45,X,del(X)(q13). Imaging, surgical exploration, and histopathologic evaluation confirmed that a pelvoabdominal mass originated from the left ovary and was a mixed germ cell tumor containing yolk sac tumor and mature teratoma components. At presentation, the patient also reported symptoms consistent with gender dysphoria. This case highlights the wide phenotypic variability of mosaic Turner syndrome and reinforces the importance of accurate neonatal sex assignment in individuals with DSD. It further emphasizes the need for healthcare providers to remain vigilant for such presentations to enable prompt, tailored, and comprehensive management.