Morris syndrome is a hereditary disease characterized by the development of female sexual characteristics in the presence of a male karyotype (XY). The symptoms of this pathology have a wide range of severity – from a phenotypically full-fledged woman to a full-fledged man with a number of intermediate variants, on which the classification of this condition is based. Diagnosis is based on the results of gynecological or urological examination, ultrasound examinations of pelvic organs, karyotype studies and molecular genetic analyses. There is no specific treatment for this disease, a variety of surgical interventions are used to improve the quality of life of patients.
Morris syndrome (testicular feminization syndrome) is a genetic disease that affects individuals with a male karyotype and leads to the development of various female sexual characteristics in them up to complete feminization. Disorders of this type have been recorded for a long time, immediately after the discovery of the chromosomal basis of sex and karyotype studies, but this disease was first described by American gynecologist John Morris in 1953. He studied known at that time (more than 80) patients with male pseudohermaphroditism and identified a number of family cases, which allowed him to define Morris syndrome as an X-linked recessive hereditary disease.
In some sources, this pathology can be found under the name of Morris syndrome. Currently, it has been established that the occurrence of Morris syndrome is approximately 1 case per 20-60 thousand male newborns, but the frequency of carrying the pathological gene among women is unknown. This disease is the cause of almost 20% of cases of male pseudohermaphroditism and causes a significant proportion of all varieties of primary amenorrhea.
Research in the field of modern genetics has revealed the molecular genetic mechanisms of Morris syndrome – these were mutations of the AR gene localized on the X chromosome. The expression product of this gene is a protein receptor for testosterone and its metabolites (mainly dihydrotestosterone), the presence of which ensures the body’s response to male sex hormones. To date, more than 300 different types of AR gene mutations have been identified, leading to testicular feminization syndrome. All of them are recessive in nature, so women (by karyotype) with a homologous X chromosome can only act as a carrier and transmit this disease to their sons with a 50% probability.
Due to violations in the structure of the AR gene, the protein-receptor encoded by it turns out to be defective, depending on the type of mutations, its reaction to the effects of testosterone and similar compounds changes. In the most severe course of Morris syndrome, the receptor becomes completely unable to interact with male sex hormones, so the body’s cells lose sensitivity to them, retaining it to estrogens (mainly estradiol). This leads to the development of the body completely according to the female type in the presence and functioning of the testicles. Some other types of Morris syndrome are caused by maintaining sensitivity to testosterone, but at an extremely low level, which causes a wide range of clinical manifestations. The activity of Sertoli cells that secrete testosterone in any form of Morris syndrome persists and may even be slightly increased.
The extreme form of Morris syndrome has the following pathogenesis – even at the stage of embryonic development, due to the lack of influence of testosterone, due to the insensitivity of the body to it, the formation of female genital organs occurs. A “blind” vagina is formed, the split scrotum becomes large labia, the rudiments of the phallus – the clitoris. At the stage of puberty, there is also a complete lack of cell reaction to testosterone, therefore, with Morris syndrome (full type), body tissues are influenced only by female sex hormones. This circumstance leads to the formation of pronounced secondary sexual characteristics – lush breasts, “model” forms, distribution of adipose tissue according to the female type, a thin voice. However, menstruation and, moreover, the possibility of pregnancy in this case are completely excluded, since patients do not have a uterus and hormonal factors necessary for the menstrual cycle.
Classification and symptoms
Morris syndrome is characterized by an extensive spectrum of manifestations and varieties of the disease, a special classification of this pathology has been developed for their systematization. First of all, all forms of this condition are divided into two groups – complete and incomplete. The full form occurs when the body is completely insensitive to testosterone and is characterized by a full-fledged female phenotype. Usually a healthy girl is born who, at first glance, does not have any developmental abnormalities. With the onset of puberty, such patients often become very beautiful (with a “model appearance”) due to the prevailing influence of estrogens. However, at the same time, they do not have hair loss in the armpits and pubis, menarche does not occur – often it is amenorrhea at the age of 14-16 years that becomes the reason for going to the doctor, where the testicular feminization syndrome is revealed as part of a gynecological study.
The incomplete form of testicular feminization syndrome is characterized by a much more diverse clinical picture. As a rule, the cause of this form of pathology is defects in testosterone receptors, which do not lead to a complete loss of sensitivity, but only to its significant decrease or violation. According to the classification adopted in 1996, there are five main forms or degrees of incomplete Morris syndrome:
- 1st degree (male type) is characterized by a typically male phenotype without any deviations. In extremely rare cases, there may be a high voice and signs of gynecomastia in adolescence. At the same time, the processes of spermatogenesis are almost always disrupted, therefore, male infertility is observed in patients with this type.
- 2nd degree (predominantly male type) – this variant of the disease is manifested by more pronounced disorders of virilization and formation of the genitals, although phenotypically patients are men. They often have hypospadias, the development of micropenis or a combination of these signs is possible. Patients with this variant often have gynecomastia and uneven deposition of subcutaneous fat.
- 3rd degree (ambivalent type) – characterized by a pronounced decrease in the penis, which becomes similar to the clitoris. The scrotum is divided so much that its halves resemble large labia, hypospadias, cryptorchidism are often observed. With this type, pelvic enlargement, gynecomastia, and relatively narrow shoulders are also noted.
- 4th degree (predominantly female type) – in this form of testicular feminization syndrome, patients are women according to their phenotypic characteristics, but their clitoris is often hypertrophied, the urogenital sinus forms a short blind vagina. Often, with this variant of the disease, there is such a violation as the fusion of the labia.
- 5th degree (female type) – patients with this form are phenotypically women, practically no signs of virilization are found in them except for a slightly enlarged size of the clitoris. During puberty, it can increase even more, reaching the size of a micropenis.
Patients also often have inguinal hernias due to impaired patency of the testicles through the inguinal canal. Complications of hypospadias can be a variety of inflammatory processes in the urinary system (urethritis, pyelonephritis). Cryptorchidism threatens in the future with malignant degeneration of testicular tissues, which is the most severe complication of this disease.
The main methods of diagnosing this condition are gynecological or urological examination, ultrasound examination, study of hereditary history, molecular genetic analysis and determination of the level of sex hormones. First of all, it is possible to diagnose incomplete forms of testicular feminization syndrome of 2-5 degrees, since disorders in the structure of the genitals are noticeable already at the birth of a child. Upon examination, a neonatologist may suspect the presence of a genetic disease and prescribe additional clarifying studies. The combination of such malformations with normal or even elevated testosterone levels in the blood and cryptorchidism speaks in favor of the presence of testicular feminization syndrome.
The incomplete form of the disease of the 1st degree and the full type of pathology in most cases are determined much later. The reason for the treatment of men (according to their phenotypic characteristics) with Morris syndrome to specialists is often suspicion of infertility. Semen analysis at the same time reveals azoospermia, the patient has a history of cryptorchidism (often eliminated surgically), inguinal hernias. In this case, it is possible to confirm the presence of Morris syndrome only with the help of genetic diagnostics. The full form of the disease is most often diagnosed at the age of 14-15, when girls turn to a specialist due to the lack of menstruation. During gynecological examination, they have a “blind” vagina, closed in the upper third, ultrasound studies reveal the absence of the uterus and its appendages. At the same time, testicles may be detected that are located at various stages of descent into the scrotum – located within the abdominal cavity, inguinal canal, occasionally in the labia.
The concentration of testosterone in testicular feminization syndrome corresponds to the level of a healthy man or even slightly exceeds it. At the same time, the amount of estrogens does not reach the lower level of the norm for girls of the same age. The study of the hereditary history can detect signs of X-linked transmission of the disease. Molecular genetic diagnosis of testicular feminization syndrome is performed by a geneticist using automatic sequencing of the AR gene sequence or other techniques. It is also possible to detect the carrier of the pathological form of the gene in healthy women and prenatal diagnosis of this disease.
Treatment of Morris syndrome of the full type is often limited to simple removal of the testes, followed by hormonal correction (if necessary). This is required for the prevention of seminoma and other forms of malignant degeneration of testicular tissues. Such patients, who have been brought up as girls since childhood, may need psychological help after diagnosis. Therapy of incomplete testicular feminization syndrome is characterized by a large number of plastic surgeries to recreate the usual appearance of the genitals, breasts, and optimal functioning of the urinary system. Patients with any form of this disease are infertile, which also often requires the help of psychologists.
Prognosis and prevention
The prognosis regarding the survival of patients is quite favorable – with a full form of pathology, patients can live a normal life of a woman, while having a male karyotype. Incomplete forms with properly performed surgical correction of disorders and malformations often also do not lead to severe and life-threatening complications. Testicular feminization syndrome is particularly threatened by testicular cancer in the case of cryptorchidism, so it must be eliminated – by removing the testes into the scrotum (with a male phenotype) or by removing the glands (in the case of a female phenotype).
Prevention of Morris syndrome is carried out by genetic detection of the carrier of a pathological gene with a burdened hereditary history and, if confirmed, by prenatal diagnosis of this pathology.