Introduction
Mixed gonadal dysgenesis is a type of sexual development disorder that causes the defective or incomplete formation of the gonads (testis or ovary). This occurs due to anomalies or abnormalities of the sex chromosome or genes involved in forming gonads at birth. Therefore, this reproductive system condition is called a congenital developmental disorder. Mixed gonadal dysgenesis leads to the formation of atypical gonads and gets replaced by streak or functionless gonads. The development of the gonads in a person is a genetic process of the X and Y chromosomes in the body that forms the ovary and testis (gonads). Thus, gonadal dysgenesis occurs due to the failure of this genetic process during fetal development.
What Are the Causes of Mixed Gonadal Dysgenesis?
Children with mixed gonadal dysgenesis (MGD) have different cells with different chromosome patterns. For example, a child has a 45, X / 46, XY chromosome pattern in this condition. This difference in chromosome pattern is called mosaicism, and in the case of sex chromosomes, it is known as sex chromosome mosaicism. The 45, X indicates the loss of one sex chromosome, and these chromosome patterns can exist in many different forms. For example, Turner syndrome also has a 45, X/45, X0 pattern.
Mixed gonadal dysgenesis can cause the development of gonads on a different path than the typical one and leads to underdeveloped gonads, also known as dysgenetic gonads or streak gonads. These gonads sometimes do not make sex hormones; other times, they may have ovary or testis tissues present and can make sex hormones. As a result, people born with mixed gonadal genesis have reproductive parts typical for a girl, boy, or both depending on the type and amount of hormones they produce.
Another cause of mixed gonadal dysgenesis can be endocrine disruption, which can lead to sexual developmental disorders and cause gonadal dysgenesis.
What Are the Symptoms of Mixed Gonadal Genesis?
The symptoms of mixed gonadal genesis are as follows:
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Hypogonadotropic hypogonadism is caused by a defect in the hypothalamus or pituitary gland.
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Streak gonads.
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Primary amenorrhea is the absence of periods or menses for up to 15 years, even after developing secondary sexual characteristics and average body growth.
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Failure or inability to develop secondary sexual characters.
How Does Mixed Gonadal Dysgenesis Affect Reproductive Growth?
Mixed gonadal dysgenesis affects reproductive growth in the following ways:
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Vagina - People with mixed gonadal dysgenesis usually have a small vagina and urogenital sinus. The joining of the urine tube and vagina is referred to as urogenital sinus, and it causes a single-hole opening on the outside instead of two holes.
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Genitals - The genitals usually have standard features of both a girl and a body. The penis appears small, whereas the clitoris is large.
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Uterus or Womb - A uterus may or may not be present in people with mixed gonadal dysgenesis.
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Gonads - A person with mixed gonadal dysgenesis can have an underdeveloped gonad or streak on one side and a typical gonad on the other.
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Puberty - The type of hormones produced during puberty is responsible for the changes at this stage. For example, if a person's body has testosterone at puberty, deepening of the voice, genital growth, and facial hair growth occur at puberty.
What Are the Risk Factors Associated With Mixed Gonadal Dysgenesis?
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Low levels of follicle-stimulating hormone (FSH).
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High levels of luteinizing hormone (LH).
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Endocrine disruption.
What Are the Complications Associated With Mixed Gonadal Dysgenesis?
The complications include:
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Infertility or impaired fertility.
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Miscarriage.
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Still babies.
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Ovarian failure.
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Webbed necks.
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Malformed babies.
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Streak gonads.
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Delayed puberty.
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Primary amenorrhoea.
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Ambiguous genitalia.
Which Diseases Are Associated With Mixed Gonadal Dysgenesis?
The diseases associated with mixed gonadal dysgenesis:
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Kidney cancer - Wilm’s syndrome.
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Kidney disease - Denys-Drash syndrome.
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Heart and kidney disorders - Cardiorenal syndrome.
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Partial depletion of the X chromosome.
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Perrault syndrome - Sensorineural hearing loss and XX gonadal dysgenesis.
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Osteoporosis - Decreased bone strength.
How Is Mixed Gonadal Dysgenesis Diagnosed?
Mixed gonadal dysgenesis is diagnosed as follows:
Medical Examination or Testing at Birth: The doctor examines a person and may find undescended testicles. The testicles are present in the groin and not in the scrotum. But during the physical test, the doctor may not feel the presence of an underdeveloped (streak) gonad. Also, the differentiation between a boy and a girl cannot be made by examining the genitals as they don't appear typical.
The medical examination includes the following tests:
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Hormone Level - The blood test checks the type and quantity of hormones produced by gonads in the body.
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Karyotype - This blood test checks a person's X and Y chromosomes and finds out if any mixed pattern of chromosomes is present.
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Laparoscopy - This is a surgical procedure used by healthcare providers to check for the reproductive parts inside the human body with the help of a small camera. The doctor may also extract the body tissues during the process for biopsy testing.
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Pelvic Ultrasound - This imaging or radiological test to check for gonads and the uterus inside a person's body.
How Can We Treat Mixed Gonadal Dysgenesis?
Mixed gonadal dysgenesis can be treated in the following ways:
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Medical Treatment - People born with mixed gonadal dysgenesis are routinely monitored by the healthcare provider for growth, development, and overall health of the body. The hormone levels are also regularly checked for other health conditions, including kidney, hearing, vision, and heart-related problems. In addition, changes in the body due to hormone levels at puberty are also treated. This includes testosterone therapy for the growth of the penis, facial hair growth, and hoarseness of the voice, and estrogen therapy for the development of breasts, strong bones, and sexual characteristics.
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Surgical Treatment - People with mixed gonadal dysgenesis are not often treated surgically at birth. If a person has undescended testicles, they are surgically brought down into the scrotum, and an underdeveloped (streak) gonad is surgically removed to prevent cancer growth in the future. The medical team plans other surgical procedures according to the patient's needs.
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Psychosocial Treatment - Mixed gonadal dysgenesis is a life-long medical condition that often stresses family and the person and affects the patient's overall well-being. Therefore, the healthcare team must address the mental health issues of such patients and their families. This can help the person develop and live a comfortable life with their gender and feel confident about themselves.
Conclusion
In typical cases, 46 chromosomes are present in every individual, each having one “X” and one “Y” chromosome or a pair of two “X” chromosomes. However, this genetic pattern can be disrupted for various reasons during fetal development and can cause gonadal dysgenesis in a person. However, treatment options are available for mixed gonadal dysgenesis, but the manifestations depend upon the condition's cause and severity.
