Gender confusion during embryonic development can lead to abnormalities in the gonads and external genitalia at birth, known as hermaphroditism. The sex of the child at the time of delivery is very sensitive to the parents, and failure to make a “boy” or “girl” determination at birth, and failure to technically manage it later, can have profound and long-lasting negative effects on both parents and child I. Classification of gender anomalies (a) Hypogonadal differentiation syndrome – chromosomal abnormalities Because of sex chromosomal abnormalities, hypogonadal differentiation can occur, and these patients are characterized by the presence of bilateral striated gonads, the impact of both gonads can be unequal, or both are absent or asymmetrical. Chromosomal abnormalities can lead to true gonadal hypogonadism, mixed gonadal hypogonadism and true hermaphroditic syndromes. (ii) Androgen excess syndrome Hypermasculinity in women can be due to congenital adrenal hyperplasia syndrome or adrenogenital syndrome, the so-called female pseudohypergynosis. To prevent early abortions, progestational preparations can produce manifestations similar to those of exogenous androgens. 21-hydroxylase gene deficiency (95%) is the main cause of adrenogenital syndrome. If the child is raised as a boy, the diagnosis is often easily missed. If the child is raised as a girl, an early diagnosis can be made with severe androgenesis of the external genitalia and contradiction of the 46,XX karyotype. These malformations can even be fatal if misdiagnosed, as hyperkalemia and hyponatremia due to salt and glucocorticoid deficiency can cause cardiac arrhythmias and/or severe dehydration. In the individual presentation the patient has a markedly enlarged clitoris and overdeveloped scrotum-like labia, presenting a male-like appearance. The gender assignment of such patients should be female. (iii) Androgen deficiency syndrome Children with male chromosomes may have male pseudohermaphroditism syndrome due to androgen deficiency, an abnormality caused by a deficiency in the production of testosterone due to an enzyme deficiency in the metabolic conversion of cholesterol to testosterone. Androgen receptors may be mildly or completely deficient (incomplete feminization of male pseudohermaphroditism, type 1). Mild cases may be raised as boys; in more severe cases of variant, combined with testicular feminization, assignment to the female sex should be mandatory as appropriate. II. Clinical diagnosis When a newborn is born with ambiguous external genitalia in appearance, it is important to make a quick gender determination and screen accurately so that the emotional impact on the family can be minimized, otherwise, subsequent changes will be very painful. Identification of the type of defect can be made quickly by two screening criteria: first, the presence of symmetrical or asymmetrical gonads, and second, the presence of chromatin or X chromosomes (Barr vesicles), or the lack of fluorescence at the end of the long arm of the Y chromosome. Once the main types have been correctly determined, the particular pathological etiology can be determined in a meticulous plan. Symmetry of the gonads is determined by the relative position of one testicle to the other, both above or below the external ring opening. If the gonads are symmetrical, although both are located above or below the inguinal canal, they may be abnormal on an etiologic basis, and a biochemical defect will affect both gonads. In female pseudohermaphroditism and in most cases of true hermaphroditism, there is more than one X chromosome (Barr microsomes) in the karyotype and inactive X chromosomes can be found in the nucleus. Conversely, no Barr microsomes are found in the chromosomes of patients with male pseudohermaphroditism and mixed gonadal hypogonadism, and detection of Barr microsomes can serve as a screening test. In addition, analysis of the distal end of the long arm of the Y chromosome by a labeling method (not by Barr vesicles) has resulted in negative fluorescence detection of the Y chromosome in patients with female pseudohermaphroditism and true hermaphroditism. This test has now been replaced by PCR analysis with Y-specific probes such as SRY, which allows for a differential diagnosis within 24 hours of birth with an accuracy of 80-90%. Laboratory tests include buccal mucosal smears for Barr microsomes, Y chromosome fluorometry, PCR with Y-specific probes, and also blood cell cultures for karyotype analysis. Serum tests for electrolytes include sodium and potassium, glucose, sex hormone levels, 17-hydroxyprogesterone before and after stimulation with HCG, testosterone, dihydrotestosterone, and MIS. molecular probes are now available for detection of deletions of 5α-reductase, SRY, MIS, MIS receptor, 21-hydroxylase, and P450 enzymes or for detection of single base pair mutations. Ultrasound of the pelvis and perineum may reveal the presence of Mullerian structures, and further radiographic studies may be performed if necessary. Careful use of sinus cavity radiographs with a rigid adapter placed at the perineal opening can reveal anatomic abnormalities of the urogenital sinuses and accurately depict the vaginal access to the urethra. Further cystography can be performed for a complete evaluation. Treatment Female perineal reconstruction Female perineal reconstruction is used for female pseudohermaphroditism with karyotype 46,XX or for adrenogenital syndromes with significant masculinization during embryogenesis, as well as for those syndromes with insufficient masculinization with karyotype 46,XY including mixed gonadal hypogonadism, true hermaphroditism, and male pseudohermaphroditism. Female perineal reconstruction includes clitoral reduction to preserve clitoral sensitivity and erectile function, transformation of the scrotum into a thinner and longer labia majora, flap transfer to form the labia minora, and vaginoplasty. The more masculine the infant, the more the vagina enters the urethra proximally to build a common urogenital sinus, and in severe cases the vagina may enter the proximal end of the external urethral sphincter, requiring a higher level of skill for repair. Reconstruction of the male perineum This nonmasculine appearance can be due to an enzyme deficiency resulting in insufficient testosterone production, abnormal testosterone receptors, or a complete or incomplete conversion of testosterone to dihydrotestosterone due to a 5α-reductase deficiency. In these patients, the perineum is combined with a severely recurved micropenis, the urethra usually opens at the penile-scrotal junction, the scrotum is severely divided, and the foreskin covers the dorsal aspect of the penis like an overgrown turban. Since many of these children have a small penis, they are treated with testosterone before surgical repair is performed. The first correction is due to the downward curvature of the penis. Since it is necessary to release all the fibrous scar from the ventral side up to the cavernous split, which usually causes bleeding, such children with hypospadias and micropenis should undergo staged surgery to prevent the new urethra from soaking in the hematoma. Scrotal splitting is usually combined with penile scrotal transposition, where the scrotum is located above the dorsal aspect of the penis. If it is more severe, the scrotal skin needs to be transferred to the underside. This repair needs to be delayed because the blood supply to the dorsal flap can be impaired if the procedure is performed too early. Some cases of true hermaphroditism and mixed gonadal hypoplasia have a mullerian duct that connects to the prostatic capsule. If urine is backed up into the Mullerian structures, recurrent urinary tract infections and/or epididymitis may result, requiring removal of the Mullerian structures but careful separation along the course of the vas deferens to protect the vas deferens. The entrance to the vas deferens can be palpated on the side of the seminiferous tubules. If the testis is in the abdominal cavity, a testicular fixation is required to adequately separate the spermatic cord so that it has sufficient length to reach the scrotum. If the testis is absent, a testicular prosthesis should be implanted early to prevent scrotal atrophy. The preserved gonads are placed in the appropriate part of the scrotum, but must be followed up to be alert for cancer.