In the periods when radiological devices such as ultrasonography were not in use, whether a pregnant woman’s child would be a girl or a boy would be the most curious issue around the parents and the whole family. The first question asked after birth is a girl? The question of whether he was a man or not was almost second to none in some families.
Today, with the determination of the sex of the child while in the mother’s womb, the first question after birth is actually the question of whether he is healthy or not.
External genital appearance suggests that the baby is a boy, a girl, or somewhere in between. The sexual confusion in the latter case is also called ambigous genitalia or intersex. may require urgent intervention. Since the majority of births in our country are performed by inexperienced people without the supervision of physicians and due to the lack of timely examinations by pediatricians, significant delays in diagnosis may occur, as well as false sexual descriptions and results up to the death of the child.
Families mostly; They tend to define children whose external genitalia look like both sexes with the sexual identity they desire. Most of the parents have no information about this subject. However, determining the exact shape of the child’s gender as soon as possible will prevent problems that may arise in the future and are impossible to repair. It should not be forgotten that their families, being ashamed of the situation in question, prevent the child from seeing even the people around him, and that they can pass the event over.
It should be noted that the number of such children, which is not very rare, reaching the doctor is less than it should be.
In order to better understand the issue of gender confusion, we will briefly touch on normal gender development in the fetus in the womb. However, some words (in terms of terminology) will be given their short meanings.
Fertilization: Fertilization
Chromosome: Structures in the cell nucleus that determine the characteristics and sex of the person.
Chromosomal: Chromosomal
Sperm:Male reproductive cell.
Ovum: The female reproductive cell.
Gene: Structures that determine individual characters located on chromosomes.
Genetics: Genetic, hereditary
Embryonic period: The period from fertilization to birth in the womb.
Ductus-Ductal: (Belonging to the canal-canal)
Wolf duct:Embryonic structure that develops male internal genital structures.
Müller duct: Embryonic structure that can develop female internal genitalia.
Gonad: The embryonic structure that will form the testis or ovary according to the gender of the child during the intrauterine period.
Phallus: The embryonic structure that will form the penis in the male and the clitoris in the female.
Hypospadias: In boys, the opening of the urinary tract, which should normally be opened to the penis head, shows an opening in the lower part of the penis
The normal sexual development of the child (fetus) in the womb:
Sexual differentiation following fertilization of sperm and ovum in the uterus; It occurs as a result of the development of the internal and external genitalia in the male or female direction in intrauterine life. This development occurs in three steps.
Determination of chromosomal and genetic structure during fertilization and gender; Depending on the genetic structure, the gonad develops in the direction of the testis or ovary, and according to the direction of this development, the internal and external genital structures acquire characteristics specific to that genus. There is no distinction between male and female gonads until the fifth week in the embryonic period.
In the fetus, the bipotential gonad begins to differentiate in the direction of the testis (male) at around 5 weeks, and the differentiation in the direction of the ovary (female) is at 12-14. It begins in the third week. Before the embryonic gonad differentiates into testis or ovary, a double ductal (duct) system develops in both sexes. From these internal genital channels, Wolf’s canal provides the formation of male internal genital structures and Müller’s canal provides the formation of female internal genital structures. One of them becomes atrophied according to the state of the sex formed. In the fetus that will become a male, the Wolf duct forms the internal male genital organs, while the Müller duct atrophies.
The outer part of the primitive gonad in the fetus is called the “cortex” and the inner part is called the “medulla”. Also, an embryonic formation called the genital tubercle (genital protrusion) that will enable the development of the external genital organs in both males and females manifests itself.
In addition to the 46+X chromosome, which determines the genetic characteristics of the person from men, there is a Y (sex that determines the male genetic structure) chromosome. .
In females, the chromosome structure is 46+XX. The last pair of chromosomes in both males and females are sex chromosomes.
Development of male sex: In cases where the fetus has genotype (46+XY), testicles and cords (semen-carrying channels) begin to develop from the medullary part of the gonad from the seventh week onwards.
External genital structures in both sexes are the same until the 8th week in the fetus. (Genital protrusion) has the capacity to undergo changes in both sexes.
Hormones released from the testis after the 8th week in the male sex ensure the development of the internal and external genital organs of the fetus. The hormonal effect also causes the brain to be stimulated (in a virilizing direction). migration begins. Generally, both testicles complete their descent into the scrotum before the child is born.
Gender Development in the Female Direction:
In the fetus whose genotype is 46+XX, ovaries from the gonad (female ovary)12. It begins to form in the th week. In the following weeks, the internal and external genital organs in the female fetus complete their development in the female direction.
In order to better understand the issue of genital confusion (suspicious genitalia-intersex) in children, we will describe the etiological (reasons) reasons roughly under three headings.
1-Gonadal (primitive germ organ) differentiation
disorders:
a.Mix gonadaldysgenesis (differentiation disorders of gonads towards testis or ovary in fetus)
b . Dysgenetic (impaired) development of gonad despite XX sexual genotype
c. Impaired development of gonad despite XY sexual genotype
d. True hermaphroditism (having both testicles and ovaries in the same person)
2-Female Pseudohermaphroditism (46-XY- despite the male sex chromosome, they show female-like external genitalia
3-Male pseudohermaphroditism (46+XY) Despite the male sex chromosome, they show a female-like external genitalia
The groups briefly classified above under three headings will be briefly evaluated below:
1. Gonadal Differentiation Disorders:
They have an important place among children with suspicious genitalia. One or two gonads (testicle or ovary in the fetus) are dysgenetic (structural disorders). Especially, gonadal disorders in XY structure are different degrees of suspicious external genital anomalies. They are responsible. In most of such suspicious cases, there is asymmetry in the internal and external genital organs. Classically, there is a defect in the structure of one gonad testis and the other gonad (9800). 705)
2-Girl Pseudohermaphroditism:
The genetic structure of these children is (female) 46+XX. Since their gonads do not have testicles, their internal and external genital organs have developed in the female direction. As a result of being under the influence of androgenic (male) hormones during their development in the mother’s womb, their external genital structures show a masculine structure to varying degrees. The masculine change in the external genital structure is related to the amount and duration of androgens that the child is exposed to in the womb. Hyperplasia (excessive growth in the adrenal gland) and excessive secretion of adrenal gland hormones with androgen effect are the main causes. Salt loss occurs in 70-80% of congenital adrenal hyperplasia in children.
Androgenic lesions (male hormone-secreting tumors) seen in the ovaries of girls will also be briefly mentioned under this heading. These rare tumors cause a masculine appearance in the external genital organs of the child in the prepubertal period, enlargement of the clitoris, hair growth, absence of cramps or cessation of menstruation. These types of tumors in the ovary, called “arrhenoblastoma”, can be located by ultrasonography, Computed Tomography (CT) and Magnetic resonance (MR). These usually occur in dysgenetic (genetically damaged) ovaries. It can be seen on one side or both ovaries. In 50% of cases, the tumor can be felt on palpable abdominal examination. If the tumor is bilateral, both ovaries should be removed together with the tumor. If a girl has a Y chromosome in her genetic structure (dyskinetically), both ovaries should be removed. Because the risk of developing a malignant tumor is always quite high in an innocent-looking ovary.
3- Male Pseudohermaphroditism:
Gonads in the fetus in the mother’s womb are testicles and genetically 46+XY male cases. Early diagnosis is very important in determining the sex the child will be raised. Genetically 46+ Although they show an XY structure, there is a partial androgenic (testosterone and some of the adrenal gland hormones) hormone insensitivity. In such fetuses, insensitivity of external genital organs to hormones, anomalies such as micropenis (small penis), undescended testis and hypospadias at varying degrees in children may occur together or alone. Unfortunately, in some cases, the diagnosis may be delayed until the secondary sex characteristics fail to develop during puberty. Despite high androgen levels in these children, their inability to use them causes gynecomastia (breast enlargement) in boys due to the conversion of these hormones to estrogen (female sex hormone).
Again in patients evaluated in this group, insufficiency in the formation of testosterone (biosynthesis) (despite XY-male genetic structure) prevents the development of internal and external genital organs to varying degrees. However, their incidence is very rare.
The normal penis length in a newborn baby is 3.6±0.7 cm and the diameter is 1.1±0.2 cm. The penis length below 1.9 cm in a newborn baby is called micropenis. Micropenis is a hormonal disorder in the 14th week of pregnancy. Gonadal hormone deficiency may be due to hypogonadism in the fetus, or it may be idiopathic (with unknown cause) in some cases. The most common cause of penile smallness occurs as a result of insufficient secretion of an enzyme called gonadotropin-releasing factor, which is secreted from the brain and enables the secretion of gonadotropin hormone from the gonad. Rarely, in some babies, growth hormone (Growth hormone) secretion deficiency or testicular failure (Robinow syndrome) is the cause of micropenis. In such children, the cause of micropenis should be revealed by a pediatric surgeon, pediatric urologist and pediatric endocrinologist.
To stimulate the growth of the penis in such children (500 units are given every other day for 4 weeks after the age of 1, in order to make the diagnosis according to the response of the penis to the hormone.) In addition, before puberty, a sufficiently large penis is given. Androgen origin (male hormone) hormone should be used to have them.
4-True Hermaphrotism:
It is the least common intersex (suspicious genitalia) disease. It is epidemic (regional) in African Bantus. It is well developed (development) in these patients. male and female gonads (testicle or ovary) are found together. In this association, the testis or ovary can be found separately, one testis and the other ovotestis (both testis tissue and ovary tissue together in the same gonode) or one ovary and the other ovotestis. According to the type of gonad (sperm and/or ovum-female egg of the related genus), embryonic components that will form the testis in the male and the ovary in the female on the related side, as well as the Wolff duct on the side that will be the testis, and the Müller duct on the side that will be the ovary, and which provide the development of the internal genital organs. develops.
While testicular and ovarian tissues are observed in normal structures, testicular tissue is seen in the center in the ovotestis structure and the ovarian tissue is seen around it. In approximately 80% of these patients, 46+XX chromosome (female) structure and Barr body (mouth in females) There is a positivity in the sample taken from the mucosa, which is seen under the microscope and indicates that the child is in the female genetic structure. In the other 20%, 46+XX or 46+XX/46+XY mosaic chromosome structure and variable Barr body positivity or negativity are detected
The actual cause of hermaphroditism is unknown. It is suggested that it is the result of the fusion of the short arm of the Y chromosome to the X chromosome. The most important criteria in the planning of the treatment to be chosen in this disease are the age at diagnosis and the size of the phallus. In such cases, structures developing from Wolff’s duct (internal genital structures) and testicular tissue should be made. Cliteroplasty to the phallus Labiums are formed by opening the labioscrotal fold. After puberty, a functional female gender identity is gained by vaginoplasty using the large intestine. It is removed, the hypospadia is repaired, if any. In the pubertal period, secondary sex characters are developed by giving external testosterone and a testicular prosthesis is placed.
Approach to Children with Questionable Genital Structure (Intersex)
Such children should be promptly investigated in the following order.
a-Detailed history
b-Physical examination
c-Chromosome analysis
d-Examination of blood biochemistry
a-Detailed history:
a- Detailed family history
It starts with obtaining detailed information about the child’s prenatal period and especially the mother during pregnancy. Conditions such as hormonal deficiencies in individuals), early menopause, osteoporosis, delayed puberty, ammonia, infertility, suspicious genital structure, and whether there are children who have been lost during birth or in the neonatal period (overwork of the adrenal gland accompanying salt loss) should be investigated in detail.
It should also be questioned whether the mother used androgen-containing (male) hormones during pregnancy (it can be used in maternal ovarian or adrenal tumors).
b-Physical Examination
Genital examination should be performed by a physician who is highly experienced in this field.
A newborn with an empty scrotum should not be evaluated as male even if he is male in terms of chromosomal structure and bilateral undescended testicles, without detailed examination.
Congenital adrenal hyperplasia (overwork of the adrenal gland), secretion of (extremely) androgenic (male hormone) due to the insufficiency of the hormone called cortisone, affects the external genital organs of the female fetus (fetus) in a way that takes a masculine appearance. This situation can sometimes mislead even the doctor.
It should be considered as suspicious genitalia with an empty scrotum, small penis (micropenia), and severe hypospadias (opening of the urinary tract to a more distal place instead of the glans penis).
The symmetry of the gonads, that is, both gonads above or below the outer inguinal ring, is very important. Since the pathological mechanism affects both gonads in both male and female pseudohermaphrodites, the gonads are located symmetrically. While the gonads can be felt on both sides in male pseudohermaphrodites, the gonads can be seen in the abdomen in female pseudohermaphrodites. While the gonad is palpable on one side, it is not palpable on the other. According to the asymmetric or symmetrical location of the gonads, the physician is directed towards the true diagnosis.
c-Chromosome Analysis
Genotype (genetic chromosomal sex) can be determined within 48 hours with the (fluorescent in situ hybridization) technique to be performed with DNA probes specific to X and Y sex chromosomes from peripheral lymphocytes. Very rarely, chromosome analysis from other tissues may be required to exclude mosaicism.
Examination of d-Blood Biochemistry
In some cases with genetically 46+XY chromosome structure, masculine development of external genitalia is insufficient. They are referred to as male pseudohermaphrodites. Because of the insufficient development of the external genital organs of these patients with normal testicles; a) Insufficient testosterone production (due to the deficiency of some enzymes necessary for testosterone production) b) Testosterone cannot become active as a result of the deficiency of 5 άreductase enzymes in the target organ (testicle and penis), c) Absence or insufficient receptors in the external genital organs to respond to testosterone are held responsible. .
Although they are usually raised as males, in male pseudo-hermaphrodites, the child’s penis cannot prevent a slightly enlarged clitoris size, and the penile structure is insufficient for erection. For this reason, it would be appropriate, even a necessity, to give a girl identity to such children who were diagnosed as boys and to be brought up in this direction.
In congenital adrenal hyperplasia (excessive secretion of hormones by the adrenal gland), however, androgenic (masculine) intermediates, which are highly increased as a result of insufficient enzyme for cortisone synthesis, affect the external genitalia of the female fetus in a masculine appearance. The appearance can range from clitoris enlargement alone to the development of a male penis with a normal urinary tract opening at the tip. In this type, which is most common in suspicious genitalia, the blood biochemistry should be examined immediately and it should be determined whether it is a salt-losing type. In the salt-losing type, medical treatment should be started quickly.
All female pseudohermaphrodites should be reared as females. These are normal female patients with fertility characteristics.
Mixed gonadal dysgenesis (impaired development of the gonad) cases also have insufficient masculine development in the external genitalia.
The patient’s child’s sex chromosome genotype shows mosaicism (abnormal) as 46+XY /45+XO. Often, there is a dysgenetic testis (pathologically) on the one hand, and an abnormal (pathologically-structured) ovary on the other. Since the external genitalia are generally in the form of a girl, there is no mistake in being raised in terms of the gender of the patient. Rarely, in some cases, babies can be raised as boys because the phallus (primitive genitalia) is large.
After taking the necessary samples for chromosome and blood chemistry examinations in children with suspicious genitalia, various radiological examinations should be performed in order to define the current anatomical structure in detail. The presence of uterus and/or gonads should be determined by pelvic ultrasonography. A brief idea can be obtained about the presence of testis. If there is, endoscopy (cystoureteroscopy) should definitely be performed to understand the connection site. Laparoscopy or laparotomy (by looking with an instrument or surgically opening the abdomen) can be performed for understanding the internal genital structure and for gonad biopsies if necessary.
Treatment
The child whose gender is suspected should be examined by a specialist physician after birth and his/her gender should be determined with the tests he/she deems appropriate. It should be done by a team of geneticists, child psychologists, and child endocrinologists.
The secret of success in both medical and surgical treatment depends on diagnosis as early as possible. If the child has suspicious genitalia, gender identity and name should not be given. Gender identity should be determined between 3-6 months. In some rare cases, as a medical necessity It should also be kept in mind that the child may grow up under a different sexual identity other than his or her genetic gender (original gender). It is inevitable for the child to encounter sexual confusion and psychological problems that cannot be compensated and treated in later ages. It should be kept in mind that such problems can lead people to commit suicide.
Suspicious genitalia is a disease after all, and the family does not need to be ashamed of it and hide the child. As I mentioned above, most of them can be treated with medication, but in some cases with the addition of minor surgical interventions to the medication.
The biggest mistake in this regard; It is the giving of the sexual identity attributed to the child in the direction of the sexual expectation of the family or by the inexperienced physician or other health personnel in a situation where there is a doubt about the sexual identity following the birth of the child.
In the treatment part; By mentioning medical and surgical treatment and their techniques, I do not intend to confuse the readers’ minds further on this already complex issue.
