MO029CLINICAL CHARACTERISTICS AND PATHOGENIC GENES OF CONGENITAL SOLITARY KIDNEY WITH REPRODUCTIVE SYSTEM MALFORMATION*

Background and Aims Congenital solitary kidney – one category of congenital anomalies of the kidney and urinary tract (CAKUT) may combine with other system malformations such as reproductive, cardiac, skeletal system, and so on. Our study analysed the clinical characteristics among congenital solitary kidney patients and their reproductive system malformations. And further work about probable pathogenic genes was explored. Method The information of CAKUT patients who were indicated by Doppler ultrasound was collected. The clinical and imaging features including reproductive system abnormalities were retrospectively reviewed in patients with congenital solitary kidney. In patients with Mayer-Rokitansky- Küster-Hauser (MRKH) syndrome, a disorder of congenital agenesis of uterus and vagina, whole exome sequencing was performed. Rare variants in CAKUT-related genes were analysed. Trio analysis was conducted to identify de novo mutations. Results We identified 209 patients with congenital solitary kidney from July 20, 2017 to July 19, 2020 among 1160 CAKUT patients in Peking Union Medical College Hospital. There were 152 females. The average age of congenital solitary kidney patients was 35.26±18.42 years when they were diagnosed. 53.2% showed different degrees of proteinuria and hematuria. Serum creatinine elevating was proved 13.1% and 40% in women and men separately. Among 81 females who also had a gynecological ultrasound report, 88.9% combined with genital malformation, oblique vaginal septum syndrome 48.7%, the Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome 22.2%, malformed uterus 23.5%, vaginal atresia and other genital malformation 7%. Congenital heart disease, complete transposition of viscera, and scoliosis were also found in some patients with congenital solitary kidney. Furthermore, based on the whole exome data of 443 patients with MRKH syndrome, seven function-lost mutations were confirmed. And also two De nove mutations (NOTCH2 (NM_024408.3: c.703A>T(p.Thr235Ser), ESRRG (NM_001243512.1:c.-169-8delT)), one homozygous patients with parents heterozygous (NM_133433.3:c.8084C>T(p.Thr2695Me) were identified as possible pathogenic genes caused CAKUT. Conclusion We should be aware of reproductive system malformations in CAKUT patients. Whole exome sequencing may suggest common pathogenic genes between the two kinds of diseases.

De Castro falloplasty of the with penile agenesis

Introduction. Penile agenesis (aphallia) is an extremely rare congenital disorder. At present, about 100 cases of the anomaly have been described around the world. The incidence of this congenital anomaly is estimated to be one case per 2030 million births. One of the most commonly used reconstructive procedures today is the technique proposed by Roberto De Castro in 2007. In this article, we present a clinical case of aphallia in a boy who underwent phalloplasty. Materials and methods. A newborn boy presented with aphallia, combined with abnormal development of both kidneys. At birth, the child had difficult urination through the fistula at the edge of the anus. The meatotomy and urethral dilation were performed on the fifth day of the infant`s life. On day 28 of the child`s life, surgical intervention was performed to remove the left non-functioning kidney and a right cutaneous ureterostomy because of the recurrence of febrile urinary tract infection. At 13 months, the tissue expander was installed above the pubic bone. At 16 months, the child underwent the De Castro phalloplasty technique while in the supine position. Results. The child was examined 3, 6, and 12 months after the surgical treatment. Phalloplasty has had good outcomes as evaluated by parents and surgeons. At present, the boy is under the supervision of urologists, who plan to perform further surgical treatment of the urinary system. Conclusion. Phalloplasty, in the case presented, had a good cosmetic result. In our opinion, it proved to be the correct initial stage of treatment for aphallia, an extremely rare genital malformation.

Genital malformation case

Jacobs reported the following interesting case at the Societ Belge de gyn. e d'obst. July 24, 1892: X .., 24 y., Strong constitution; at 14, pains in the lower abdomen appeared, which, repeating periodically (monthly), intensified and in recent years the patient had to lie in bed for 15 days every month. There was no menstrual bleeding.

SUN-LB12 Prenatal Trenbolone Exposure and External Genital Malformation: A Case Report

Background Trenbolone is a synthetic anabolic steroid used for muscle growth in livestock. Human use is not FDA approved. The active metabolite, 17β trenbolone is 3 times more potent an androgen than testosterone propionate. Prenatal trenbolone exposure in rats results in female offspring with external genital malformations including an increased anogenital distance (AGD). We now report a case of prenatal trenbolone exposure in humans. Clinical Case A 10 hour old baby delivered vaginally at 37 6/7 weeks of gestation with a birth weight of 3615 grams was admitted to the NICU for concern of ambiguous genitalia. Baby was born to 30 year old G6P3 mother who was HIV positive and adequately treated with Triumeq. She had irregular cycles prior to conception and pregnancy recognized at 14 weeks. Unlike her previous pregnancies, during this pregnancy she had acne and mildly increased facial hair. Prenatal cell-free DNA screening was 46XX and ultrasound showed female genitalia. The 9 year old half-sister and 5 year old brother are healthy. No family history of early neonatal deaths. On arrival blood glucose was 55 mg/dL (45-90). On exam baby had no obvious facial dysmorphic features or midline defects. Hand creases were normal and no extremity edema was noted. Genitalia appeared symmetrical and, showed prominent soft tissue of clitoris without corpus enlargement. No gonads were palpable in the groin or labioscrotal folds. Significant posterior labioscrotal fusion was noted. Anogenital ratio was 0.8 (normal <0.5). A single orifice at the base of the clitoral hood was noted, consistent with likely urogenital sinus. Additional history provided by mother included her disclosure of use of 200 mg of IM trenbolone weekly for 5 weeks, for muscle building, prior to her knowledge of being pregnant. Multidisciplinary care included pediatric endocrinology, genetics, pediatric urology, and pediatric infectious disease. Labs at 24 hours of life: Sodium - 139 mmol/L (131-144), Potassium - 5.3 mmol/L (3.2-5.7), Serum glucose - 75 mg/dL (45-90), Random cortisol - 34.1 mcg/dL (1.0-10.0), 17 hydroxyprogesterone - 124 ng/dL (<460), CAH diagnostic panel - normal with exception of elevation in Progesterone - 3400 ng/dL (5-53), Newborn screening - normal, Chromosomal analysis - 46,XX and absent SRY, Ultrasound pelvis - normal Müllerian structures and bilateral intra-abdominal gonads present. Baby was hemodynamically stable, voided well, gained weight by discharge on DOL 4. Baby was stable on follow-up in endocrinology clinic on DOL 10. Surgical repair of anatomic malformation to be performed at 6 months of age by urology team. Conclusion To our knowledge, this is the first report of virilization of female offspring following human prenatal exposure to trenbolone. Women must be cautioned that trenbolone poses risks of external genital malformation to the developing fetus.

Psychosexual Outcome of Men with Non-Corrected Hypospadias

Objective: Hypospadias is a common penile malformation, in which the urethral opening is on the underside of the penis. It is usually surgically corrected in early childhood. Severe types of hypospadias are corrected to solve functional problems. Mild types are mainly operated to achieve a better cosmetic result under the assumption that surgery improves psychosexual adjustment and quality of life. However, data on the outcome of non-operated men is scarce and therefore, this assumption is not evidence based. This study compares psychosexual outcome of men with non-corrected hypospadias to men without a genital malformation. Design and Method: In an ongoing cross-sectional survey, 21 men with noncorrected hypospadias (mean age: 48.71 years, SD: 10.33) and a control group of 21 age matched, non-affected men (mean age: 48.05 years, SD: 9.72) were asked to answer a penile self-perception score (PPS) and a questionnaire regarding their psychosexual adjustment. Results: Men with non-corrected hypospadias and controls reported the same level of sexual satisfaction and number of sexual partners. Men with non-corrected hypospadias were neither more often ashamed nor more often bothered because of their penile appearance. However, they had significantly less positive PPS. Conclusions: Although men with non-corrected hypospadias had an impaired penile self-perception, they were neither ashamed nor bothered due to their penile appearance and they reported the same level of sexual satisfaction as non-affected men. These results suggest that there is a subgroup of men with non-severe types of hypospadias, who do not suffer if left without surgical correction for their hypospadias in childhood.