Reifenstein syndrome

　　How is Reifenstein syndrome caused? The following is a brief description.

　　1. Etiology

　　The etiology of Reifenstein syndrome is the same as that of testicular feminization, caused by point mutation of the AR gene. The mutation mainly occurs in the DNA binding region and androgen binding region, mostly involving the substitution of basic amino acids, such as histidine replacing arginine or methionine replacing valine, etc.

　　2. Pathogenesis

　　These conservative amino acid mutations result in a lesser degree of loss of AR function than testicular feminization, and the clinical manifestations of the patients are relatively mild, only partial androgen resistance.

　　Generally, mutations in the same AR gene will show similar clinical manifestations, but in fact, the same mutation can show different clinical manifestations. For example, the replacement of arginine at position 855 of the androgen-binding domain of the AR gene with histidine results in the clinical manifestation of the syndrome of Reifenstein, while replacement with cysteine or leucine results in testicular feminization, indicating that there are other factors involved in the process of masculinization caused by androgens.

　　The main manifestations of the syndrome of Reifenstein are that the external genitalia can be perineal or scrotal urethral fistula, blind pouch vagina, clitoral hypertrophy, and cryptorchidism. It can also be small penis with partial fusion of the labioscrotal folds or bilobed scrotum, without uterus and fallopian tubes, and incomplete development of epididymis and vas deferens. During puberty, pubic hair, axillary hair, and male breast development appear, with small testes and azoospermia. Pathological histological examination shows that spermatogenesis is停留在 the primary spermatocyte stage, plasma LH and testosterone levels increase, the production rate of testosterone and E2 increases, and the increase in E2 levels is related to the appearance of breast development and other feminization signs during puberty, but the degree of feminization is lighter than that of testicular feminization. There are no other special complications in the syndrome of Reifenstein.

　　The clinical manifestations of the syndrome of Reifenstein are heterogeneous. The external genitalia can be perineal or scrotal urethral fistula, blind pouch vagina, clitoral hypertrophy, and cryptorchidism. It can also be small penis with partial fusion of the labioscrotal folds or bilobed scrotum, without uterus and fallopian tubes, and incomplete development of epididymis and vas deferens. During puberty, pubic hair, axillary hair, and male breast development appear, with small testes and azoospermia. Pathological histological examination shows that spermatogenesis is停留在 the primary spermatocyte stage, plasma LH and testosterone levels increase, the production rate of testosterone and E2 increases, and the increase in E2 levels is related to the appearance of breast development and other feminization signs during puberty, but the degree of feminization is lighter than that of testicular feminization.

　　The clinical manifestations of the syndrome of Reifenstein are similar to those of 5α-reductase 2 deficiency or 17β-HSD3 deficiency, especially in prepubertal patients. The elevation of MIF levels in plasma after the first year of birth and after puberty is androgen resistance syndrome. Fibroblast culture of the genital skin biopsy can evaluate the degree of abnormality in the quantity and quality of androgen receptors, and amino acid sequence analysis of the AR gene can determine the site of mutation.

　　This disease is X-linked recessive inheritance, with no clear preventive information. The key points for postoperative care are as follows:

　　1. After surgery, be careful not to wet the wound when washing your face or taking a bath.

　　2. Pay special attention not to let the baby scratch the wound to prevent infection. In case the wound is torn, apply antiseptic medication in a timely manner.

　　3. Avoid spicy and other刺激性 food.

　　4. Patients undergoing laser treatment should also pay attention to sun protection.

　　5. Let the scab on the wound fall off naturally.

　　6. Avoid sudden forceful massage of the affected limb, etc.

　　7. Avoid prolonged standing.

　　8. Continue to wear elastic stockings to promote venous return in the lower extremities and avoid the formation of post-thrombotic syndrome.

　　9. Keep bowel movements regular, prevent constipation, and increased abdominal pressure during defecation can easily lead to thrombosis detachment.

　　10. Eat more fresh vegetables and fruits, eat less greasy, spicy and other foods, and keep the mood comfortable.

　　11. Quit smoking and drinking.

　　The following is a brief description of the examinations that should be done for Refan syndrome.

　　1. Pathological and histological examination.This examination can show that spermatogenesis is stopped at the primary spermatocyte stage.

　　2. Ultrasound examination.This examination can show whether there is underdevelopment of the uterus and fallopian tubes, epididymis and vas deferens.

　　Dietary principles for Refan syndrome, briefly described as follows: The diet should strive for balance, with at least 50% to 60% of carbohydrates, including vegetables, brown rice, avocados, konjac, seeds, stone fruits, grains, lean meat, fish, yogurt, and raw cheese. High-fiber diets are helpful for internal environmental balance and can be combined with fiber and protein foods (for example, bran cakes with raw cheese or almond jam).

　　The patient's gender orientation is determined by the patient's age and the anatomical function of the external genitalia at the time of diagnosis. From the point of view that most patients only show limited response to exogenous testosterone treatment, it is wise to raise most patients as girls.

　　2. For female gender patients, genital reconstruction involves the removal of testicles, and estrogen replacement therapy is given in adolescence.

　　1. For male gender patients, genital reconstruction can be performed, and the testicles within the labia scrotal fold can be preserved. In adolescence, anabolic androgen replacement therapy is given in doses exceeding physiological levels. Correction of hypospadias, breast augmentation surgery, and orchidopexy for cryptorchidism. Due to small penis size, high doses of testosterone can be administered to promote penile growth and maintain normal sexual function.