Clinical characteristics of Chinese patients with Herlyn-Werner-Wunderlich syndrome: a multicentric study

BackgroundHerlyn-Werner-Wunderlich syndrome (HWWS), also named as Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome, is a rare female genitourinary malformation disease featured by uterine didelphys, obstructed hemivagina and ipsilateral renal anomaly. In addition to the abnormalities of the reproductive system, it's been reported that HWWS patients can present with other rare extragenital malformations, such as scoliosis, abnormal cardiac development and intestinal malrotation, which might need proper evaluation and intervention by other specialties (1,2). Due to the low incidence of HWWS, previous studies were limited to case reports. There is no clinical study with relative large sample size focusing on the extragenital malformations of HWWS patients so far.ObjectiveTo analyze the proportion of extragenital malformations in a large cohort of Chinese patients with HWWS.MethodsThis is a nationwide multicenter, retrospective study. Patients diagnosed with HWWS and treated at 19 centers from January 2015 to June 2021 were included. HWWS patients with complete medical history records and screening examinations for urinary system, skeletal system, cardiovascular system and other systems were included. Then the prevalence and types of concomitant extragenital malformations were analyzed.This study was approved by the Ethics Committee of Peking Union Medical College Hospital (Project No. ZS-1858).ResultsAmong 307 HWWS patients, a total of 255 patients were included in this study. Among them, 206 patients (80.8%) presented with dysmenorrhea or periodic lower abdominal pain, and 116 patients (45.5%) complained of vaginal bloody/purulent discharge. In terms of combined deformities of skeletal system, 37 cases (14.5%) were combined with congenital or idiopathic scoliosis, 18 cases (7.1%) were combined with lumbar or sacral spina bifida, and a few cases with hip dysplasia and coccyx hypogenesis. As for urinary system, the vast majority (93%) of the patients presented with renal agenesis, other abnormalities such as ectopic ureter orifice, megaureter, ectopic kidney, renal dysplasia, duplication of the collecting system, and extrarenal pelvis can also be observed. As for cardiovascular system, a total of 8 patients (3.2%) had cardiac abnormalities, including redundant anterior leaflets of the mitral valve, bicuspid aortic valve, and atrial septal defect. In addition, 5 patients (2%) had malformations of other systems, including anal atresia, ectopic colon, congenital vaginal-rectal fistula, vaginal-vesical fistula, and congenital strabismus. It's reported that the prevalence of scoliosis is 0.5-1/1000 while that of congenital cadiovascular malformations is 19.93/10,000 live births (3,4). Compared with the existing epidemiological research data, the incidence of scoliosis in HWWS patients was significantly higher than that in the normal population, but there was no significant difference in the incidence of cardiovascular system malformations.ConclusionsPatients with a definite diagnosis of HWWS should complete the evaluation of the urinary system and skeletal system to screen possible developmental abnormalities and provide timely intervention. Herlyn-Werner-Wunderlich syndrome (HWWS), also named as Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome, is a rare female genitourinary malformation disease featured by uterine didelphys, obstructed hemivagina and ipsilateral renal anomaly. In addition to the abnormalities of the reproductive system, it's been reported that HWWS patients can present with other rare extragenital malformations, such as scoliosis, abnormal cardiac development and intestinal malrotation, which might need proper evaluation and intervention by other specialties (1,2). Due to the low incidence of HWWS, previous studies were limited to case reports. There is no clinical study with relative large sample size focusing on the extragenital malformations of HWWS patients so far. To analyze the proportion of extragenital malformations in a large cohort of Chinese patients with HWWS. This is a nationwide multicenter, retrospective study. Patients diagnosed with HWWS and treated at 19 centers from January 2015 to June 2021 were included. HWWS patients with complete medical history records and screening examinations for urinary system, skeletal system, cardiovascular system and other systems were included. Then the prevalence and types of concomitant extragenital malformations were analyzed.This study was approved by the Ethics Committee of Peking Union Medical College Hospital (Project No. ZS-1858). Among 307 HWWS patients, a total of 255 patients were included in this study. Among them, 206 patients (80.8%) presented with dysmenorrhea or periodic lower abdominal pain, and 116 patients (45.5%) complained of vaginal bloody/purulent discharge. In terms of combined deformities of skeletal system, 37 cases (14.5%) were combined with congenital or idiopathic scoliosis, 18 cases (7.1%) were combined with lumbar or sacral spina bifida, and a few cases with hip dysplasia and coccyx hypogenesis. As for urinary system, the vast majority (93%) of the patients presented with renal agenesis, other abnormalities such as ectopic ureter orifice, megaureter, ectopic kidney, renal dysplasia, duplication of the collecting system, and extrarenal pelvis can also be observed. As for cardiovascular system, a total of 8 patients (3.2%) had cardiac abnormalities, including redundant anterior leaflets of the mitral valve, bicuspid aortic valve, and atrial septal defect. In addition, 5 patients (2%) had malformations of other systems, including anal atresia, ectopic colon, congenital vaginal-rectal fistula, vaginal-vesical fistula, and congenital strabismus. It's reported that the prevalence of scoliosis is 0.5-1/1000 while that of congenital cadiovascular malformations is 19.93/10,000 live births (3,4). Compared with the existing epidemiological research data, the incidence of scoliosis in HWWS patients was significantly higher than that in the normal population, but there was no significant difference in the incidence of cardiovascular system malformations. Patients with a definite diagnosis of HWWS should complete the evaluation of the urinary system and skeletal system to screen possible developmental abnormalities and provide timely intervention.