Cuerpos desgener[iz]ados: rescatando las experiencias de personas intersex como usuarias del sistema de salud público Chileno / Corpos desgener[iz]ados: resgatando as experiências de pessoas intersexuais como usuárias do sistema público de saúde chileno / Desgener[iz]ated bodies: rescuing the experiences of intersex people as users of the Chilean public health system

Introducción: La intersexualidad comprende condicionesinfrecuentes donde una persona nace con una anatomíasexual diferente del binario hombre-mujer; esto suponehabitar un cuerpo fuera de lo inteligible y estigmatizado.Históricamente, desde la heteronorma, el modelo biomédicoha buscado normalizarles quirúrgicamente para asignarprecoz y arbitrariamente un sexo-género armónico con lagenitalidad. Desde los Derechos Humanos, estas prácticasson cuestionadas por colectivos Intersex.Materiales y método: Estudio de caso, entre años 2019 y2020; técnica de entrevista en profundidad a dos usuariosadultos de los Policlínicos de Urología y Endocrinología de unhospital público en Santiago, Chile; se utilizó la fenomenologíade Husserl para comprender la experiencia en el sistema desalud de las personas intersex. El análisis de la informaciónse basó en la propuesta de Colaizzi.Resultados: Se reconocieron unidades de significado principalese imbricadas, cuyas esencias permitieron describir el fenómenode: ser niño y habitar el espacio hospitalario, vivir con lacondición actualmente, y la experiencia de utilizar el sistemade salud siendo adulto.Conclusiones: Se identificaron diversas estrategias de agenciatanto en el espacio hospitalario como el cotidiano, medianteun proceso personal y silencioso de aprendizajes sobre lasimplicancias de ser intersexual.(AU)

Introduction: Intersexuality includes extremely rareconditions where a person is born with a sexual anatomydifferent from the male-female binary; this supposesinhabiting a body outside the intelligible, configuringa stigma. Historically and from the heteronorm, thebiomedical model has sought to surgically normalizethem in order to precociously and arbitrarily assigna gender in harmony with genitality. From HumanRights, these practices have been questioned byIntersex groups.Materials and method: During the years 2019 and2020, case studies were carried out through in-depthinterviews with two adult users of the Urology andEndocrinology Polyclinics of a public hospital atSantiago, Chile; Husserl's phenomenology was usedto visualize the phenomenon according to how it isexperienced by the subjects who carry it, using theprocedure described by Colaizzi as an informationanalysis plan.Results: Main and overlapping units of meaning wererecognized, whose essences allowed describing thephenomenon of: being a child and inhabiting thehospital space, currently living with the condition,and the experience of using the health system as anadult, with new and own meanings.Conclusions: Various agency strategies were identifiedboth in the hospital space and in everyday life, througha personal and silent process of learning about theimplications of being intersex.(AU)

Introdução: Intersexo compreende condições rarasem que uma pessoa nasce com uma anatomia sexualdiferente do binário masculino-feminino; Isso significahabitar um corpo fora do que é inteligível e estigmatizado.Historicamente, a partir da heteronormação, o modelobiomédico buscou normalizá-los cirurgicamente paraatribuir precoce e arbitrariamente um sexo-gêneroharmônico com a genitalidade. A partir dos DireitosHumanos, essas práticas são questionadas por gruposintersexuais.Materiais e método: Estudo de caso, entre os anos de2019 e 2020; técnica de entrevista em profundidadecom dois usuários adultos das Policlínicas de Urologiae Endocrinologia de um hospital público de Santiago,Chile; A fenomenologia de Husserl foi utilizada paracompreender a experiência de pessoas intersexuaisno sistema de saúde. A análise das informações foibaseada na proposta de Colaizzi.Resultados: Reconheceram-se unidades de significadoprincipais e sobrepostas, cujas essências permitiramdescrever o fenômeno de: ser criança e habitar oespaço hospitalar, viver atualmente com a condição e aexperiência de usar o sistema de saúde na fase adulta.Conclusões: Foram identificadas várias estratégiasde agenciamento tanto no hospital como na vidaquotidiana, através de um processo pessoal e silenciosode aprendizagem sobre as implicações de ser intersexo.(AU)

Psychological support for individuals with differences of sex development (DSD).

OBJECTIVE: Congenital conditions with atypical development of chromosomal, gonadal, or anatomic sex characteristics are referred to as Differences of Sex Development (DSD). Psychosocial care is recommended to be an integral part of clinical management for individuals with DSD. Few studies have examined the perceived need for, utilization of and the opinions of individuals with DSD regarding psychological support. METHODS: This cross-sectional study was part of a European multicentre study in 14 different medical centres in six countries. In total, 1040 individuals with DSD participated in a patient-reported outcome questionnaire asking about experiences and opinions regarding psychological support in DSD care. RESULTS: A majority of the participants reported that they had not received psychological support, in childhood and/or adolescence (70.6%, n = 692) nor in adulthood (67.9%, n = 661). Need for psychological support in childhood and/or adolescence was reported by 51.3% (n = 503), need for psychological support in adulthood, was reported by 49.5% (n = 482). The majority (80.2%; n = 718) agreed with the statement that people with DSD should always be offered psychological support. According to 78.7% (n = 697) of the participants, parents of children with DSD should always be offered psychological support. CONCLUSION: Our findings support the existing consensus that psychological support should be an integral part of DSD care. The discrepancy between received and perceived need for psychological support suggests that individuals with DSD experience barriers to access mental health care services. Psychosocial and psychological services for children, adolescents and adults should therefore be available and offered throughout the lifespan to individuals with DSD.

46,XX disorder of sex development associated with skin abnormalities due to homozygous R-Spondin 1 loss of function mutation.

A child, who was reared as male, presented in his early childhood to the endocrine clinic with penoscrotal hypospadias which was noticed at birth. On examination, he had both gonads in the scrotal sacs with complete scrotal fusion, rugosities and chordee with a single opening. He had increased palmoplantar skin desquamation. As an initial part of the workup, karyotyping was done, which was 46,XX. To rule out the most common cause of 46,XX disorder of sex development (DSD) in phenotypical males (SRY - Sex Determining Region Y gene - translocation), fluorescent in situ hybridisation for SRY was done, which was negative. Whole exome sequencing revealed a homozygous loss of function mutation in the R-Spondin1 gene. Here we report a rare case of 46,XX DSD with loss of function mutation in the R-Spondin1 gene associated with skin abnormalities.

One-stage surgical case management of a two-year-old Arabian horse affected by male-pseudo hermaphroditism.

A two-year-old Arabian horse presented for abnormal external genitalia and dangerous stallion-like behavior was diagnosed with disorder of sexual development (DSD), also known as intersex/hermaphroditism. Standing 1-stage surgical procedure performed under sedation, and local anesthesia to concurrently eliminate stallion-like behavior, risk of neoplastic transformation of intraabdominal gonads, and to replace ambiguous external genital with a functional, and cosmetically more acceptable anatomy. Step-1) Laparoscopic abdominal exploration and gonadectomy; Step-2) Rudimentary penis resection and perineal urethrostomy. The horse tolerated surgery well (combined surgery time 185 min) with no complications. At macroscopic examination of the gonads, they resembled hypoplastic testis-like tissues. Microscopic examination confirmed presence of seminiferous tubules, Leydig and Sertoli/granulosa cells. Cytogenetic evaluation revealed a 64,XX karyotype, SRY-negative. The stallion-like behavior subsided within days post-operatively. Long-term follow-up revealed the genitoplasty site healed without urine scalding or urethral stricture. The owner satisfaction was excellent and the horse could be used post-surgery as an athlete.

Disorders of Sex Development: Experience at a Tertiary Care Hospital in Bangladesh.

In newborns, it is an emergency to decide the appropriate sex for rearing and eventual prevention associated metabolic disturbances. The birth of a baby with ambiguous genitalia inevitably precipitates a crisis for the baby and its family. This retrospective analysis of hospital data was designed to determine the chromosomal and etiological diagnosis of children presented with suspected disorders of sex development (DSD) according to the newer DSD consensus document. We retrospectively analyzed the available medical records of all patients admitted into the inpatient departments of Dhaka Shishu (Children) Hospital, Dhaka, Bangladesh from January 2014 to December 2019, and all patients with the diagnosis of DSD in the hospital record were initially selected for the study. A total of 60 admitted cases with a disorder of sex development were classified according to the new DSD classification. 46XX DSD were 63.3% (n=38), 46XY DSD were 33.3% (n=20), sex chromosome DSD were 3.3% (n=2). Among 38 cases of 46XX DSD, the most common cause was congenital adrenal hyperplasia (97.0%, n=37), one was 46XX testicular DSD. However, among 46XY DSD cases, partial androgen insensitivity/5α-reductase deficiency (50.0%, n=10) was most common disorder. Other causes of 46XY DSD included congenital adrenal hyperplasia (20.0%, n=4), testosterone synthesis defect (20.0%, n=4), testicular regression syndrome (n=1) and persistent Mullerian duct syndrome (n=1). Sex chromosome disorders are mixed gonadal dysgenesis (n=1), chimeric ovotesticular DSD (n=1). In this study, 46XX DSD was the commonest of all, showing the predominance of congenital adrenal hyperplasia, especially salt-losing type. Early detection and prompt treatment may help reduce mortality and morbidity from these acute life-threatening conditions.

Sperm function is required for suppressing locomotor activity of C. elegans hermaphrodites.

Sex differences in sex-shared behavior are common across various species. During mating, males transfer sperm and seminal fluid to females, which can affect female behavior. Sperm can be stored in the female reproductive tract for extended periods of time and used to fertilize eggs. However, the role of either sperm or embryo production in regulating female behavior is poorly understood. In the androdioecious nematode C. elegans, hermaphrodites produce both oocytes and sperm, enabling them to self-fertilize or mate with males. Hermaphrodites exhibit less locomotor activity compared to males, indicating sex difference in behavioral regulation. In this study, mutants defective in the sperm production and function were examined to investigate the role of sperm function in the regulation of locomotor behavior. Infertile hermaphrodites exhibited increased locomotor activity, which was suppressed after mating with fertile males. The results suggest that sperm, seminal fluid, or the presence of embryos are detected by hermaphrodites, leading to a reduction in locomotor activity. Additionally, females of closely related gonochoristic species, C. remanei and C. brenneri, exhibited reduced locomotor activity after mating. The regulation of locomotion by sperm function may be an adaptive mechanism that enables hermaphrodites lacking sperm or embryo to search for mates and allow females to cease their search for mates after mating.

[Clinicopathological analysis of gonadal differentiation of sex development disorder].

Objective: To investigate pathological features and differential diagnosis in the gonads with disorder of sex development. Methods: Thirty-six cases of clinically diagnosed hermaphroditism with gonadal biopsy in the Department of Pathology, the Seventh Medical Center of People's Liberation Army General Hospital from April 2007 to July 2021, were collected. All biopsy pathological sections were reviewed, and the gonadal cases with abnormal pathological morphology were screened out. The clinical and imaging data and karyotype of these cases were reviewed. Additional immunohistochemical staining was performed and relevant literature was reviewed. Results: Seven cases of ovotesticular disorder of sex development (OTDSD) were identified, which were characterized by the presence of testicular and ovarian differentiation in the same individual. All patients were under 15 years old and presented with abnormal appearance of external genitalia, and the ratio of male to female was 2∶5. Ultrasonography showed testicular structure in all female patients and cryptorchidism in all male patients. The most common karyotype was 46, XX. One case with undifferentiated gonadal tissue (UGT) and one case with streak gonads were screened out. UGT germ cells were neither in seminiferous tubules nor in follicles, but randomly distributed in an ovarial-type interstitial background, sometimes accompanied by immature sex cords. Streak gonads resembled UGT without germ cells. FOXL2 was positive in granulosa cells, but negative in Sertoli cells. SOX9 expression was opposite. OCT4 was weakly positively/negatively expressed in oocytes and positively expressed in the germ nuclei of UGT. Conclusions: Four differentiation patterns need to be identified in the gonadal biopsy: ovarian differentiation, testicular differentiation, undifferentiated gonadal tissue and streak gonad. The positive expression of SOX9 indicates testicular differentiation, while the positive expression of FOXL2 confirms ovarian differentiation, and the expression of both markers in the same tissue indicates ovotestis differentiation. It is very important to identify UGT, because that has a high probability of developing into gonadoblastoma in the future.

Expanding the phenotype of copy number variations involving NR0B1 (DAX1).

46,XY gonadal dysgenesis (GD) is a disorder of sex development due to incomplete gonadal differentiation into testes, resulting in female to ambiguous external genitalia. Duplications at the Xp21.2 locus involving the NR0B1 (DAX1) gene have previously been associated with 46,XY GD. More recently, a complex structural variant not directly involving NR0B1 has been reported in 46,XY GD illustrating that the mechanism of how copy number variants (CNVs) at Xp21.2 may cause 46,XY gonadal dysgenesis is not yet fully understood. Here, we report on three families in which a duplication involving the NR0B1 gene was detected in the context of prenatal screening. This is the first report of duplications involving NR0B1 in three phenotypically normal males in two families. Fertility problems were present in one adult male carrier. The data reported here from an unbiased screening population broaden the phenotype associated with CNVs involving NR0B1, and this may aid clinicians in counseling and decision making in the prenatal context.

Clinical utility of early rapid genome sequencing in the evaluation of patients with differences of sex development.

Establishing an early and accurate genetic diagnosis among patients with differences of sex development (DSD) is crucial in guiding the complex medical and psychosocial care they require. Genetic testing routinely utilized in clinical practice for this population is predicated upon physical exam findings and biochemical and endocrine profiling. This approach, however, is inefficient and unstandardized. Many patients with DSD, particularly those with 46,XY DSD, never receive a molecular genetic diagnosis. Rapid genome sequencing (rGS) is gaining momentum as a first-tier diagnostic instrument in the evaluation of patients with DSD given its ability to provide greater diagnostic yield and timely results. We present the case of a patient with nonbinary genitalia and systemic findings for whom rGS identified a novel variant of the WT1 gene and resulted in a molecular diagnosis within two weeks of life. This timeframe of diagnosis for syndromic DSD is largely unprecedented at our institution. Rapid GS expedited mobilization of a multidisciplinary medical team; enabled early understanding of clinical trajectory; informed planning of medical and surgical interventions; and guided individualized psychosocial support provided to the family. This case highlights the potential of early rGS in transforming the evaluation and care of patients with DSD.

Disorders of sexual development: structured radiological reporting and practical approach.

Disorders of sexual development (DSD) comprise a complex group of conditions with varied clinical presentations, such as atypical genitalia, non-palpable testes, primary amenorrhea, or infertility. Besides being associated with other congenital anomalies, DSDs bear substantial ethical issues regarding assigning the sex of rearing to the child and future fertility options. Establishing the correct diagnosis is essential for the appropriate management of such cases. Various imaging modalities, such as ultrasonography, genitography, and MRI, when complemented with detailed clinical evaluation and karyotyping, are the key to diagnosing the condition. This article attempts to present a concise approach to various patterns of DSD, which will aid radiologists to solve these diagnostic dilemmas.

A prospective study on disorders of sex development in Duhok city, Kurdistan region, Iraq: Genetic, etiology and clinical presentation.

Disorders of Sexual Development (DSD) encompass all types of intersex cases and have been reported globally. However, in Iraq, studies related to DSD are scanty.  The current single-center prospective study was carried out to find out the frequency, genetic and clinical presentation of different types of DSDs in the sample population of Duhok, Iraq. The sample comprises 40 DSD patients who have been referred to Hivi Pediatric Teaching Hospital in Duhok, Kurdistan region, Iraq, from June 2017 to June 2022. We conducted karyotype-based classification, laparoscopic-based internal organ diagnosis and abdominal ultrasound to diagnose DSDs in the target population. Of the total 40 cases, 19 (47.5%) were males, and 21 (52.5%) were females. Among them, 85 % were diagnosed as peno- scrotal hypospadias, 10% had clitoromegaly and the remaining were diagnosed as under-developed female-like genitalia. The majority of the patients were diagnosed with congenital adrenal hyperplasia (CAH) (55%), 37.5% were Testicular Feminization Syndrome (TFS) and the remaining were rare categories that we did not reach final diagnosis. Laparoscopy was done for 77.5 % of the participants of whom 30% had small uterus and ovaries, 25% had Intra-abdominal testes and the remaining had testes &ovaries, Mullerian Inhibitory Factor (MIF) deficiency and TFS. The study found different types of DSDs in the target population that requires both physical and psychological intervention. Future studies should focus on evaluating DSDs in larger populations and at multi-centers to understand the condition's trajectory in the Iraqi population.

Preimplantation genetic testing and prenatal diagnosis in a family with pseudovaginal perineoscrotal hypospadias: A case report.

RATIONALE: Pseudovaginal perineoscrotal hypospadias (PPSH) is a rare autosomal recessive disorder of sex development caused by biallelic mutations in SRD5A2. PPSH is characterized by a vaginal-like blind ending perineal opening, penoscrotal hypospadias, and impaired masculinization. PATIENT CONCERNS: We reported preimplantation genetic testing and prenatal diagnosis in a family with PPSH. DIAGNOSIS: Whole-exome sequencing of the family identified 2 SRD5A2 pathogenic variants (c.578A>G and c.607G>A). Haplotype analysis showed that the variants were inherited from the previous generation of this family. INTERVENTIONS: During subsequent in vitro fertilization, preimplantation genetic testing was performed on 9 embryos. One unaffected embryo was transferred, resulting in a singleton pregnancy. OUTCOMES: The prenatal diagnosis at 20 weeks' gestation confirmed the fetus was unaffected. A healthy female infant weighing 3100 g and measuring 50 cm was delivered vaginally at 39+5 weeks of gestation. LESSONS SUBSECTIONS: This case highlights the use of preimplantation genetic testing and prenatal diagnosis to prevent the transmission of PPSH in families at risk. Our approach provides an effective strategy for identification and management of families with autosomal recessive disorders like PPSH.

Sexual antagonism in sequential hermaphrodites.

Females and males may have distinct phenotypic optima, but share essentially the same complement of genes, potentially leading to trade-offs between attaining high fitness through female versus male reproductive success. Such sexual antagonism may be particularly acute in hermaphrodites, where both reproductive strategies are housed within a single individual. While previous models have focused on simultaneous hermaphroditism, we lack theory for how sexual antagonism may play out under sequential hermaphroditism, which has the additional complexities of age-structure. Here, we develop a formal theory of sexual antagonism in sequential hermaphrodites. First, we construct a general theoretical overview of the problem, then consider different types of sexually antagonistic and life-history trade-offs, under different modes of genetic inheritance (autosomal or cytoplasmic), and different forms of sequential hermaphroditism (protogynous, protoandrous or bidirectional). Finally, we provide a concrete illustration of these general patterns by developing a two-stage two-sex model, which yields conditions for both invasion of sexually antagonistic alleles and maintenance of sexually antagonistic polymorphisms.

[Clinical, genetic, and pathological analysis in 165 children with disorders of sex development]. / 165ä¾‹å„¿ç«¥æ€§å‘è‚²å¼‚å¸¸ç–¾ç— çš„ä¸´åºŠã€é—ä¼ å­¦ä¸Žç— ç†å­¦åˆ†æž.

OBJECTIVES: To investigate the clinical phenotypes, genetic characteristics, and pathological features of children with disorders of sex development (DSD). METHODS: A retrospective analysis was conducted on epidemiological, clinical phenotype, chromosomal karyotype, gonadal pathology, and genotype data of 165 hospitalized children with DSD at Children's Hospital of Hebei Province and Tangshan Maternal and Child Health Hospital from August 2008 to December 2022. RESULTS: Among the 165 children with DSD, common presenting symptoms were short stature (62/165, 37.6%), clitoromegaly (33/165, 20.0%), cryptorchidism (28/165, 17.0%), hypospadias (24/165, 14.5%), and skin pigmentation abnormalities/exteriorized pigmented labia majora (19/165, 11.5%). Chromosomal karyotype analysis was performed on 127 cases, revealing 36 cases (28.3%) of 46,XX DSD, 34 cases (26.8%) of 46,XY DSD, and 57 cases (44.9%) of sex chromosome abnormalities. Among the sex chromosome abnormal karyotypes, the 45,X karyotype (11/57, 19%) and 45,X/other karyotype mosaicism (36/57, 63%) were more common. Sixteen children underwent histopathological biopsy of gonadal tissues, resulting in retrieval of 25 gonadal tissues. The gonadal tissue biopsies revealed 3 cases of testes, 3 cases of dysplastic testes, 6 cases of ovaries, 11 cases of ovotestes, and 1 case each of streak gonad and agenesis of gonads. Genetic testing identified pathogenic/likely pathogenic variants in 23 cases (23/36, 64%), including 12 cases of 21-hydroxylase deficiency congenital adrenal hyperplasia caused by CYP21A2 pathogenic variants. CONCLUSIONS: Short stature, clitoromegaly, cryptorchidism, hypospadias, and skin pigmentation abnormalities are common phenotypes in children with DSD. 45,X/other karyotype mosaicism and CYP21A2 compound heterozygous variants are major etiological factors in children with DSD. The most commonly observed gonadal histopathology in children with DSD includes ovotestes, ovaries, and testes/dysgenetic testes.

Sex chromosomes: How to make a hermaphrodite.

The existence of sex chromosomes complicates the evolution of cosexuality (hermaphroditism). Four new genomic studies from haploid-dominant plants show commonalities and differences in mechanisms of the evolution of cosexuality, raising questions about the genetics of sexual dimorphism and the fate of cosexual lineages.

A Case Reported With 46, XX Testicular Disorders Of Sexual Development And Its Possible Association With Dysembryoplastic Neuroepithelial Tumour.

The main factor determining differentiation of bipotential gonads into testes or ovaries is the presence or absence of SRY (sex-determining region on Y chromosome) gene. De la Chapelle syndrome is a chromosomal anomaly with chromosomal makeup of a female (46, XX) and phenotypic presentation of a male. Previously known as XX sex reversal, it is now called 46, XX testicular disorders of sexual development (DSD). Although rare, it presents as a major chromosomal anomaly, with SRY gene crossover proposed as an underlying aetiology in most patients. We report the case of a 25-year-old male who presented with infertility and was diagnosed with De 46, XX testicular DSD. He has a previous history of resected dysembryoplastic neuroepithelial tumour (DNT). The differential diagnosis of 46, XX DSD and possible association/coincidental finding of DNT have been discussed. Karyotyping should be a part of the workup for every patient who presents with infertility and has azoospermia and hypergonadotropic hypogonadism.

Serum steroid metabolite profiling by LC-MS/MS in two phenotypic male patients with HSD17B3 deficiency: Implications for hormonal diagnosis.

Although 17ß-hydroxysteroid dehydrogenase type 3 (HSD17B3) deficiency is diagnosed when a testosterone/androstenedione (T/A-dione) ratio after human chorionic gonadotropin (hCG) stimulation is below 0.8, this cut-off value is primarily based on hormonal data measured by conventional immunoassay (IA) in patients with feminized or ambiguous genitalia. We examined two 46,XY Japanese patients with undermasculinized genitalia including hypospadias (patient 1 and patient 2). Endocrine studies by IA showed well increased serum T value after hCG stimulation (2.91 ng/mL) and a high T/A-dione ratio (4.04) in patient 1 at 2 weeks of age and sufficiently elevated basal serum T value (2.60 ng/mL) in patient 2 at 1.5 months of age. Despite such partial androgen insensitivity syndrome-like findings, whole exome sequencing identified biallelic ″pathogenic″ or ″likely pathogenic″ variants in HSD17B3 (c .188 C>T:p.(Ala63Val) and c .194 C>T:p.(Ser65Leu) in patient 1, and c.139 A>G:p.(Met47Val) and c.672 + 1 G>A in patient 2) (NM_000197.2), and functional analysis revealed reduced HSD17B3 activities of the missense variants (∼ 43% for p.Met47Val, ∼ 14% for p.Ala63Val, and ∼ 0% for p.Ser65Leu). Thus, we investigated hCG-stimulated serum steroid metabolite profiles by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in patient 1 at 7 months of age and in patient 2 at 11 months of age as well as in five control males with idiopathic micropenis aged 1 - 8 years, and found markedly high T/A-dione ratios (12.3 in patient 1 and 5.4 in patient 2) which were, however, obviously lower than those in the control boys (25.3 - 56.1) and sufficiently increased T values comparable to those of control males. The elevated T/A-dione ratios are considered be due to the residual HSD17B3 function and the measurement by LC-MS/MS. Thus, it is recommended to establish the cut-off value for the T/A-dione ratio according to the phenotypic sex reflecting the residual function and the measurement method.

A Rare Case of Precocious Puberty in a Child with a Novel GATA-4 Gene Mutation: Implications for Disorders of Sex Development (DSD) and Review of the Literature.

BACKGROUND: Disorders/Differences of sex development (DSD) are often due to disruptions of the genetic programs that regulate gonad development. The GATA-4 gene, located on chromosome 8p23.1, encodes GATA-binding protein 4 (GATA-4), a transcription factor that is essential for cardiac and gonadal development and sexual differentiation. CASE DESCRIPTION: A child with a history of micropenis and cryptorchidism. At 8 years of age, he came under our observation for an increase in sexual pubic hair (pubarche). The laboratory parameters and the GnRH test suggested a central precocious puberty (CPP). Treatment with GnRH analogs was started, and we decided to perform genetic tests for DSD. The NGS genetic investigation showed a novel and heterozygous variant in the GATA-4 gene. DISCUSSION: In the literature, 26 cases with 46,XY DSD due to the GATA4 gene were reported. CONCLUSION: The novel variant in the GATA-4 gene of our patient was not previously associated with DSD. This is the first case of a DSD due to a GATA-4 mutation that develops precocious puberty. Precocious puberty could be associated with DSD and considered a prelude to hypogonadism in some cases.