{"paper_id":"ba94c0cb-7705-465c-9c86-1a97f79f0912","body_text":"Case report\nChild Kidney Dis 2019;23:124-127\nDOI: https://doi.org/10.3339/jkspn.2019.23.2.124\nISSN 2384-0242 (print)\nISSN 2384-0250 (online)\nHerlyn-Werner-Wunderlich Syndrome with Central \nPrecocious Puberty: A Case Report\nHerlyn-Werner-Wunderlich (HWW) syndrome is a rare congenital anomaly of the \ngenitourinary tract comprising uterus didelphys, obstructed hemivagina, and \nipsilateral renal agenesis. Patients with HWW syndrome usually present symp\n-\ntoms such as dysmenorrhea, abdominal pain, pelvic mass, and purulent vaginal \ndischarge. If not treated at an appropriate time, complications such as infertility, \nendometriosis, pyosalpinx, and subsequent pelvic adhesions may occur. Here, we \nreport a case of HWW syndrome in a 7-year-old-girl who was also diagnosed as \nhaving central precocious puberty. She was brought to the pediatric department \nwith chief complaints of lump in her breast and vaginal discharge. When she was \naround 2 months old, she was confirmed to have a single kidney on ultrasono\n-\ngraphy. We checked her past medical history and diagnosed her as having HWW \nsyndrome based on the results of imaging studies, including abdominal ultraso\n-\nnography and pelvic magnetic resonance imaging. She underwent treatment \nwith gonadotropin-releasing hormone analogue for 2 years. During 24 months of \nfollow-up, she showed no serious problems or complications. If renal anomalies \nare identified immediately after birth or in infancy, further screening tests should \nbe conducted prior to menstruation for determining congenital abnormalities of \nthe reproductive tract and vice versa.\nKey words: HWW syndrome, Central precocious puberty, Renal agenesis, Hemi\n-\nvagina, Uterus didelphys\nJeeho Han, M.D.\nJae Man Lee, M.D.\nGeon Hee Kim, M.D.\nSu Jin Kim, M.D.\nDepartment of Pediatrics, Myongji \nHospital, Hanyang University College \nof Medicine\nCorresponding author:\n \nSu Jin Kim, M.D.\nAddress: Department of Pediatrics, \nMyongji Hospital, Hanyang University \ncollege of Medicine, 55 Hwasu-ro \n14beon-gil, Deogyang-gu, Goyang-si \n10475, Gyeonggi-do, Republic of Korea\nTel: +82-31-810-5114\nFax: +82-31-962-4902\nE-mail: zzzing78@hanmail.net\nReceived: 29 August 2019\nRevised: 15 October 2019\nAccepted: 18 October 2019\nThis is an open-access article distributed \nunder the terms of the Creative Commons \nAttribu tion Non-Commercial License (http:// \ncrea tivecom mons.org/licenses/by-nc/4.0/) \nwhich permits unrestricted non-commercial \nuse, distribution, and reproduction in any \nmedium, provided the original work is \nproperly cited.\nCopyright © 2019 The Korean Society of \nPediatric Nephrology\nIntroduction\nHerlyn-Werner-Wunderlich (HWW) syndrome is a rare congenital ano-\nmaly of the genitourinary tract characterized by the classic triad that includes \nuterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis.\n1)\n  \nPatients with HWW syndrome usually present symptoms such as dysme-\nnorrhea, abdominal pain, pelvic mass, and purulent vaginal discharge\n2)\n.  \nSymptoms usually occur at the age of 12–13 years, immediately after the \nonset of menarche, and most patients are diagnosed from 2 months to 1 year \nafter menarche\n3)\n.  If not treated at an appropriate time, complications such as \ninfertility, endometriosis, pyosalpinx, and subsequent pelvic adhesions can \ndevelop\n4,5)\n. Therefore, diagnosis and treatment of HWW syndrome at an early \nstage are important.\nWe report the case of a 7-year-old girl with central precocious puberty who \nwas early diagnosed as having HWW syndrome through further diagnostic \n\nHan JH, et al. • HWW Syndrome with Central Precocious Puberty\n125\nwww.chikd.org\nassessments.\nCase report\nA 2 months old female baby was brought to the pediatric \nemergency department of our hospital, with cough as the \nsingle chief complaint. She had no fever, and was in good \noverall condition. In her past history, she had been healthy \nat birth, with a gestational age of 38 weeks and with a birth \nweight of 2,760 g. Also abnormal findings were not observed \nduring prenatal examinations. Laboratory investigation \nconducted by our hospital confirmed increased levels of \ntransaminases (aspartate aminotransferase, 395 IU/L and \nalanine aminotransferase, 198 IU/L), and abdominal ultra\n-\nsonography was performed for further evaluation, which \nrevealed left kidney agenesis and right kidney compensa\n-\ntory hypertrophy. No remarkable findings from the liver \nand spleen were observed. She was diagnosed with bron\n-\nchitis, reactive hepatitis and left kidney agenesis, and the \nprogress was improved after 5 days of conservative mana\n-\ngement. The need for regular outpatient follow-up was dis-\ncussed with her parents, but they did not comply. Since she \nhad not visited the hospital for a long time, further exami\n-\nnations including Dimercaptosuccinic acid (DMSA) scan \nand Voiding cystourethrography (VCUG) were not con\n-\nducted.\n7 years after the first visit, she revisited the pediatric de-\npartment with a chief complaint of lump in her breast and \nvaginal discharge. On physical examination, her height was \n130.4 cm (90th percentile) and her weight was 34.3 kg (75–\n90th percentile). Her mother’s and father’s heights were 163 \nand 183 cm, respectively. Her breast development was \nTanner stage II on sexual maturity rating, and her bone age \nshowed 10 years old using the standards of Greulich-Pyle \nmethod, which is advanced compared to chronological age. \nA gonadotropin-releasing hormone (GnRH) (gonadorelin \n100 μg, Relefact LH-RH, LG chem, Seoul, Korea ) stimula\n-\ntion test was done. Laboratory examinations revealed the \nfollowing values: luteinizing hormone (LH) peak, 42.2 \nmIU/mL; follicle-stimulating hormone (FSH) peak, 16.8 \nmIU/mL; and serum estradiol (E2) level, 47.70 pg/mL. No \nother laboratory results could be attributed to central pre\n-\ncocious puberty.\nIn general, pelvic ultrasound is not necessarily required \nfor central precocious puberty patients, but follow-up pelvic \nultrasound was performed for differential diagnosis due to \npreviously diagnosed left kidney agenesis and increased \nestradiol levels. As a result, we identified left renal agenesis \nwith left hemivaginal obstruction, separated vaginal canal, \nand cystic dilatation (Fig. 1). Subsequent magnetic reso\n-\nnance imaging (MRI) revealed a uterus didelphys and ob-\nstructive hemivagina with hydrocolpos (Fig. 2). On the \nbasis of the results of the imaging study for further evalua\n-\ntion, we diagnosed her as having HWW syndrome.\nShe underwent treatment with GnRH analogue with leu-\nA B \nC \nFig 1. Ultrasonography scan of a 7-year-old girl on August 2017, demonstrating the absence of \nthe left kidney (A) and separated vaginal canal (B). The pelvic ultrasonography scan shows cystic \ndilatation of the left vagina (2.13×0.80 cm) (C), and Mullerian duct anomaly is suspected.\n\n126\nChild Kidney Dis • 2019;23:124-127 www.chikd.org\nprorelin acetate 90 μg/kg subcutaneously every 28 days \nfrom August 2017 to July 2019 at our hospital. In an interim \ntest conducted after 6 months of treatment, her LH level \nmeasured 45 min after follow-up GnRH stimulation was \n2.3 mIU/mL (The LH peak level identified in the initial \nGnRH stimulation test was 42.2 mIU/mL). In July 2019, \nwhen the GnRH analogue treatment was terminated, she \nhad an estimated bone age of 12 years, estimated using the \nGreulich and Pyle method and her chronological age was \n10years and 10months. At the end of the GnRH treatment, \nher height was 152.6 cm (90th percentile). Her height velo\n-\ncity was maintained at approximately 5 cm per year during \nthe GnRH analogue treatment. During 24 months of fol\n-\nlow-up, no serious problems or complications arose with \nthe patient.\nWe explained to her parents that HWW syndrome usu\n-\nally presents with dysmenorrhea, pelvic pain, or pelvic \nmass after menstruation and recommended consultation \nfor surgical treatment before menarche.\nDiscussion\nThis is a case in which HWW syndrome was diagnosed \nthrough further imaging studies conducted for a patient \nwith central precocious puberty. In general, Mullerian ano\n-\nmalies have not been associated with central precocious \npuberty. However, if diagnosis is delayed in such cases as \nthis patient, blood reflux into the abdominal cavity may \nresult in endometriosis and may lead to pelvic adhesions \nand increased risk of abortion or infertility. Therefore, poss\n-\nibilities of genitourinary disease should be checked through \nhistory-taking of kidney anomalies and medical exami -\nnations. Pelvic ultrasonography can be used to identify \nchanges in the uterus, including autonomic follicular cysts, \novarian or adrenal tumors, and other genitourinary ano\n-\nmalies\n6)\n. For newborns, ultrasonography plays an impor-\ntant role in identifying Mullerian structures; however, ute-\nrine abnormalities are difficult to assess because of the \nsmall size and tubular shape of the uterus\n7)\n. Thus, it is worth \nconsidering that patients with an anomaly in the kidney \nundergo follow up ultrasonography test before the onset of \nmenstruation to detect undiscovered genitourinary dis\n-\neases such as HWW syndrome.\nIn our case, the patient had no follow-up visit within 7- \nyears after diagnosis of ipsilateral renal agenesis. However, \nthe occurrence of symptoms associated with central preco\n-\ncious puberty led to her visit in our hospital. As a result, an \nearly diagnosis of HWW syndrome was possible through \nfurther examinations after checking her past medical his\n-\ntory. Through GnRH analogue treatment, we were able to \nreduce the possibilities of complications associated with \nHWW syndrome such as dysmenorrhea, endometriosis, \npyosalpinx from early menstruation at the same time, along \nwith the treatment of central precocious puberty. If renal \nanomalies are identified, further screening tests should be \nconducted prior to menstruation for determining conge\n-\nnital abnormalities of the reproductive tract and vice versa. \nFunding\nThis research did not receive any specific grant from \nfunding agencies in the public, commercial, or not-for-\nprofit sectors.\nA \nB \nFig. 2. Magnetic resonance imaging (T2-weighted image) scans \nsuggesting Herlyn-Werner-Wunderlich syndrome. The axial \nimage shows uterus didelphys (arrow) (A). The other axial image \nshows obstructive hemivagina with hydrocolpos (arrow) (B). \n\nHan JH, et al. • HWW Syndrome with Central Precocious Puberty\n127\nwww.chikd.org\nConflict of interest\nThe Author declare that there is no conflict of interest.\nORCID iDs\nJeeho Han https://orcid.org/0000-0002-5388-0836\nJae Man Lee https://orcid.org/0000-0003-4518-9559\nGeon Hee Kim https://orcid.org/0000-0003-4955-6512\nSu Jin Kim https://orcid.org/0000-0003-0893-0512\nPatient consent\nThe study was approved by the institutional review board \n(IRB), and the consent was waived due to the nature of the \nretrospective study [IRB No. MJH 2019-06-012].\nReferences\n1. Orazi C, Lucchetti MC, Schingo PM, Marchetti P , Ferro F. Herlyn­\nWerner­Wunderlich syndrome: uterus didelphys, blind hemiva­\ngina and ipsilateral renal agenesis. Sonographic and MR findings \nin 11 cases. Pediatr Radiol 2007;37:657­65.\n2. Gholoum S, Puligandla PS, Hui T, Su W, Quiros E, Laberge JM. \nManagement and outcome of patients with combined vaginal \nseptum, bifid uterus, and ipsilateral renal agenesis (Herlyn ­\nWerner­Wunderlich syndrome). J Pediatr Surg 2006;41:987­92.\n3. Smith NA, Laufer MR. Obstructed hemivagina and ipsilateral \nrenal anomaly (OHVIRA) syndrome: management and followup. \nFertil Steril 2007;87:918­22.\n4. Wu TH, Wu TT, Ng YY, Ng SC, Su PH, Chen JY, et al. Herlyn­Werner­\nWunderlich syndrome consisting of uterine didelphys, obstruc\n­\nted hemivagina and ipsilateral renal agenesis in a newborn. \nPediatr Neonatol 2012;53: 68­71.\n5. Zurawin RK, Dietrich JE, Heard MJ, Edwards CL. Didelphic uterus \nand obstructed hemivagina with renal agenesis: case report and \nreview of the literature. J Pediatr Adol Gynecol 2004;17:37­41.\n6. Ziereisen, F., Guissard, G., Damry, N., and Avni, E. F. Sonographic \nimaging of the paediatric female pelvis. Eur Radiol 2005;15:1296­\n309.\n7 . Jiwon M. Lee. Herlyn ­Werner­Wunderlich Syndrome: A Mini ­\nreview. Child Kidney Dis 2018;22:12­6.","source_license":"CC0","license_restricted":false}