Workstream 1 - ERN eUROGEN

Workstream 1: Rare congenital uro-recto-genital anomalies

Workstream 1 (WS1) focuses on rare congenital uro-recto-genital anomalies. The Expertise Areas (EAs) covered by Workstream 1 are below.

These EAs demand require specific diagnoses and surgical correction, often in both an acute and staged approach in neonatal or childhood stages. Expertise is crucial to prevent costly and harmful secondary surgeries. Multi-disciplinary teams (MDTs) offer life-long care, enhancing post-operative well-being. ERN eUROGEN bridges paediatric and adult care gaps, enhancing outcomes through crossover and workstream transfer from WS1 to WS2. Improved transition ensures lifelong positive outcomes and disease self-management, ensuring continuous care across life stages.

NOTE: ERN eUROGEN and ERN ERNICA, the European Reference Network for rare Inherited and Congenital (digestive and gastrointestinal) Anomalies, overlap in clinical scope for Hirschsprung’s disease and Anorectal Malformations. ERN eUROGEN covers Anorectal Malformations, while ERN ERNICA addresses Hirschsprung’s disease. ERN ERNICA’s coverage for Hirschsprung’s is available on their website.

Leads

WS Lead: Wout Feitz, NL Nijmegen Radboudumc
Clinical Lead: Andrzej Gołębiewski, PL Gdansk MUG
Education Lead: Jorgen Thorup, DK Copenhagen Rigshospitalet
Research Lead: Magdalena Fossum, DK Copenhagen Rigshospitalet

EA 1.1 Complex genital reconstructions (DSDs)

Definition	Differences in sex development (DSD) is a term used to describe a group of congenital conditions in which an individual’s biological sex does not fully align with typical male or female development. DSD can involve differences in chromosomal sex, gonadal sex (the presence of testes or ovaries), hormonal sex (the levels of male or female hormones), or genital sex (the appearance of external genitalia). These variations can result in a wide range of phenotypes, from individuals with typical male or female characteristics to individuals with ambiguous genitalia or atypical reproductive systems. DSD can be caused by genetic mutations, hormonal imbalances, or environmental factors, and the condition may be diagnosed prenatally or at birth. Treatment may involve medical or surgical interventions, depending on the specific condition and the individual’s needs. DSD affects a small percentage of the population and can have significant social and psychological implications for affected individuals and their families.
Conditions & Codes	46,XX disorder of sex development induced by fetal androgens excesss: ORPHAcode 90776 / ICD-10 Code Q99.1 46,XY disorder of sex development: ORPHAcode 98085 / ICD-10 Code Q56.1 Turner syndrome: ORPHAcode 881 / ICD-10 Codes Q96.0, Q96.1, Q96.2, Q96.3, Q96.4, Q96.8, Q96.9 Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency: ORPHAcode 90794 / ICD-10 Code E25.0
EAC, Vice-EAC & ePAG	Expertise Area Coordinator: Katja Wolffenbuttel, NL Rotterdam Erasmus Vice-EAC: Verena Ellerkamp, DE Tübingen UK Patient Representative: Claire Harkin, KSA (UK)
Healthcare Providers	AT Linz Ordensklinikum, DE Munich LMUK, DE Leipzig UK, DE Mannheim UK, DE Tübingen UK, DE Ulm UK, DK Aarhus DNU, DK Copenhagen Rigshospitalet, ES Barcelona Sant Joan, ES Barcelona Vall d’Hebron, ES Madrid La Paz, ES Barcelona Fundació Puigvert, FI Helsinki HUS, FR Paris Necker, FR Paris Robert-Debré, IT Padua AOU, IT Bologna AOU, IT Rome Bambino Gesu, LT Vilnius SK, LV Riga BKU, NL Rotterdam Erasmus, NL Nijmegen Radboudumc, PL Gdansk MUG, PL Krakow USD, SE Stockholm Karolinska, SE Gothenburg Sahlgrenska, SE Uppsala Akademiska
Additional Resources	46, XY Disorders of Sexual Development. Disease InfoSearch page and Genetic and Rare Diseases Information Center page. Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Disease InfoSearch page and Genetic and Rare Diseases Information Center page. Early Genital Surgery in Disorders/Differences of Sex Development: Patients’ Perspectives. This paper by Bennecke et al. (2021) provides data on the views of 415 adult DSD patients on early genital surgery. The results are encouraging and provide powerful arguments both against a total ban on early surgery in children with DSD and also for an individualised approach. Societies for Pediatric Urology (SPU) policy statements. [Please note that these policies collectively summarise the SPU and ESPU position with respect to the evaluation and management of this condition, and represent the views of the SPU and ESPU representatives only.] The SPU Intersex Task Force and SPU Leadership have spent a significant amount of time advocating for both the rights of patients and health care professionals that care for patients with intersex and Congenital Adrenal Hyperplasia (CAH). This work has led to the development of several policy statements: Pediatric Decision Making and Differences of Sex Development: A Societies for Pediatric Urology and American Urological Association Joint Position Statement American Medical Association Code of Ethics policy for Pediatric Decision Making Societies for Pediatric Urology and the European Society for Pediatric Urology Joint Consensus Statement on the Management of Differences in Sexual Development Turner Syndrome. Disease InfoSearch page and Genetic and Rare Diseases Information Center page.

Information Video

The information video below was produced by ERN eUROGEN in coooperation with Erasmus MC. It was funded by the European Union.

EA 1.2 Bladder exstrophy/epispadias

Definition	Bladder exstrophy is a congenital abnormality in which the bladder is exposed outside of the body, as the pelvic bones and muscles that usually support it do not properly form. This can lead to a variety of associated anomalies, including problems with bladder function and urination, as well as genital and reproductive abnormalities. Bladder exstrophy is a complex condition that may require multiple surgeries and a team approach for comprehensive care.
Conditions & Codes	Bladder exstrophy: ORPHAcode 93930 / ICD-10 Code Q64.1 Exstrophy-epispadias complex: ORPHAcode 322 / ICD-10 Code Q64.1 Agenesis and aplasia of uterine body: ORPHAcode 180142 / ICD-10 Code Q51.0 Cloacal exstrophy: ORPHAcode 93929 / ICD-10 Code Q64.1
EAC, Vice-EAC & ePAG	Expertise Area Coordinator: Alaa El Ghoneimi, FR Paris Robert-Debré Vice-EAC: Gundela Holmdahl, SE Stockholm Karolinska
Healthcare Providers	AT Linz Ordensklinikum, BE Ghent UZ, BE Leuven UZ, CZ Prague VFN, DE Munich LMUK, DE Leipzig UK, DE Mannheim UK, DE Regensburg UK, DE Tübingen UK, DE Ulm UK, DK Aarhus DNU, DK Copenhagen Rigshospitalet, ES Barcelona Sant Joan, ES Madrid La Paz, ES Barcelona Fundació Puigvert, FR Paris Necker, FR Paris Robert-Debré, IT Padua AOU, IT Milan Policlinico, IT Rome Bambino Gesu, LT Vilnius SK, LV Riga BKUS, NL Nijmegen Radboudumc, NL Utrecht UMC, PL Gdansk MUG, SE Stockholm Karolinska, SE Gothenburg Sahlgrenska, SE Uppsala Akademiska
Additional Resources	Association for the Bladder Exstrophy Community. The Association for the Bladder Exstrophy Community (aBEc) is an international support network for patients and families living with bladder exstrophy. Cloacal Exstrophy. Disease Info search page and Genetic and Rare Diseases Information Center page. Exstrophy-Epispadias Complex. Disease InfoSearch page and Genetic and Rare Diseases Information Center page.
Patient Journey (Click here to download as a PDF)	Bladder-Exstrophy-Patient-Journey-October-2020

EA 1.3 Rare urological stone & kidney diseases

Definition	Rare urological stone and kidney diseases refer to a group of conditions affecting the urinary system and kidneys that are relatively uncommon and may be difficult to diagnose and treat. These conditions can include rare types of kidney stones, as well as rare genetic or metabolic disorders that affect kidney function. Treatment for rare urological stone and kidney diseases may involve a combination of medical management, dietary changes, and surgical interventions, depending on the specific condition and the individual’s needs. Due to their rarity, these conditions may require specialized care from healthcare providers with expertise in rare urological and kidney disorders.
Conditions & Codes	Classic homocystinuria, cystine stones: ORPHAcode 394 / ICD-10 Code E72.1 Genetic cystic renal disease: ORPHAcode 93587 / ICD-10 Code Q61.1 Bartter syndrome: ORPHAcode 112 / ICD-10 Code E26.8 Cystinosis: ORPHAcode 213 / ICD-10 Code E72.0 Cystinuria: ORPHAcode 214 / ICD-10 Code E72.0 Dent disease: ORPHAcode 1652 / ICD-10 Code N25.8
EAC & Vice-EAC	Expertise Area Coordinator: vacant Vice-EAC: vacant
Healthcare Providers	AT Linz Ordensklinikum, BE Leuven UZ, DE Munich LMUK, DE Leipzig UK, DE Mannheim UK, DK Copenhagen Rigshospitalet, ES Barcelona Fundació Puigvert, FR Paris Robert-Debré, LV Riga BKUS, NL Nijmegen Radboudumc, PL Gdansk MUG
Additional Resources	Bartter Syndrome. Disease InfoSearch page and Genetic and Rare Diseases Information Center page. Cystinosis. Disease InfoSearch page and Genetic and Rare Diseases Information Center page. Cystinosis Research Foundation. The Cystinosis Research Foundation’s mission is to support bench, clinical and translational research internationally to find better treatments and a cure for cystinosis. Cystinuria. Disease InfoSearch page and Genetic and Rare Diseases Information Center page. Homocystinuria. Disease InfoSearch page and Genetic and Rare Diseases Information Center page. International Cystinuria Foundation Incorporated. The Mission of the International Cystinuria Foundation is to strengthen, educate, and further the general wellbeing of the cystinuric community.

EA 1.4 Non-syndromic urogenital tract malformation

Definition	Non-syndromic urogenital tract malformations refer to a group of congenital anomalies affecting the development of the urinary and/or reproductive systems that are not associated with any known genetic syndromes. These malformations can involve various parts of the urinary and/or reproductive tract, such as the kidneys, ureters, bladder, urethra, or genitals, and can present with a range of symptoms and severity levels. Diagnosis of non-syndromic urogenital tract malformations may involve imaging studies, genetic testing, and other diagnostic tests, and treatment may involve medical management, surgical interventions, or a combination of both. The cause of many non-syndromic urogenital tract malformations is not well understood, but may involve a combination of genetic and environmental factors.
Conditions & Codes	Spina bifida: ORPHAcode 823, 268369, 268377, 268748 / ICD-10 Codes Q05.0, Q05.1, Q05.2, Q05.3, Q05.4, Q05.5, Q05.6, Q05.7, Q05.8, Q05.9 Isolated partial vaginal agenesis: ORPHAcode 96269 Septate vagina: ORPHAcode 180154 Vaginal atresia: ORPHAcode 65681 Congenital primary megaureter: ORPHAcode 617 Congenital urachal anomaly: ORPHAcode 435743 Duplication of urethra: ORPHAcode 237 Congenital agenesis of the scrotum: ORPHAcode 495879 Congenital bilateral absence of vas deferens: ORPHAcode 48 Diphallia: ORPHAcode 227 Idiopathic isolated micropenis: ORPHAcode 95707 Penile agenesis: ORPHAcode 49 Penoscrotal transposition: ORPHAcode 2842 Fetal lower urinary tract obstruction: ORPHAcode 435365 Neurogenic bladder dysfunction (Hinman syndrome & Ochoa syndrome): ORPHAcodes 84085, 2704 Caudal regression syndrome: ORPHAcode 3027
EAC & Vice-EAC	Expertise Area Coordinator: Giovanni Mosiello, IT Rome Bambino Gesu Vice-EAC: Kate Abrahamsson, SE Gothenburg Sahlgrenska
Healthcare Providers	AT Linz Ordensklinikum, BE Antwerp UZ, BE Leuven UZ, DE Munich LMUK, DE Leipzig UK, DE Mannheim UK, DE Regensburg UK, DE Tübingen UK, DE Ulm UK, DK Aarhus DNU, DK Copenhagen Rigshospitalet, ES Barcelona Sant Joan, ES Barcelona Vall d’Hebron, ES Madrid La Paz, ES Barcelona Fundació Puigvert, FI Helsinki HUS, FR Paris Necker, FR Paris Robert-Debré, IT Bergamo Papa Giovanni XXIII, IT Padua AOU, IT Turin AOU, IT Milan Policlinico, IT Rome Bambino Gesu, LT Vilnius SK, LV Riga BKUS, NL Rotterdam Erasmus, NL Nijmegen Radboudumc, NL Utrecht UMC, PL Gdansk MUG, PL Krakow USD, SE Stockholm Karolinska, SE Gothenburg Sahlgrenska, SE Lund SUS, SE Uppsala Akademiska
Additional Resources	Caudal Regression Syndrome. Disease InfoSearch page and Genetic and Rare Diseases Information Center page. Congenital Bilateral Aplasia of Vas Deferens. Disease InfoSearch page and Genetic and Rare Diseases Information Center page. Congenital giant megaureter. Disease InfoSearch page and Genetic and Rare Diseases Information Center page. Diphallia. Disease InfoSearch page and Genetic and Rare Diseases Information Center page. Duplication of Urethra. Disease InfoSearch page and Genetic and Rare Diseases Information Center page. International Federation for Spina Bifida and Hydrocephalus. Promotion and protection of the human rights of people with Spina Bifida and Hydrocephalus in accordance with the UN Convention on the Rights of Persons with Disabilities. Ochoa syndrome. Disease InfoSearch page and Genetic and Rare Diseases Information Center page. Penis agenesis. Disease InfoSearch page and Genetic and Rare Diseases Information Center page. Penoscrotal transposition. Disease InfoSearch page and Genetic and Rare Diseases Information Center page. Spina Bifida. Disease InfoSearch page and Genetic and Rare Diseases Information Center page. Vagina, absence of. Disease InfoSearch page and Genetic and Rare Diseases Information Center page.
Patient Journey (Click here to download as a PDF)	Spina Bifida Patient Journey

EA 1.5 Posterior urethral valves

Definition	Posterior urethral valves (PUV) are a congenital abnormality affecting the male urinary tract where there are thin membranes or folds of tissue located in the urethra, the tube that carries urine from the bladder to the outside of the body. These valves can obstruct or partially block the flow of urine out of the bladder, causing urinary tract problems and potentially leading to bladder and kidney damage if left untreated. PUV is typically diagnosed in male infants and may present with symptoms such as a weak urinary stream, urinary tract infections, urinary incontinence, and abdominal distension. Treatment may involve surgical correction of the valves to improve urine flow and prevent complications.
Conditions & Codes	Congenital posterior urethral valves: ORPHAcode 93110 / ICD-10 Code Q64.2
EAC & Vice-EAC	Expertise Area Coordinator: Yazan Rawashdeh, DK Aarhus DNU Vice-EAC: Rafal Chrzan, PL Krakow USD
Healthcare Providers	AT Linz Ordensklinikum, BE Antwerp UZ, BE Leuven UZ, CZ Prague VFN, DE Mannheim UK, DE Regensburg UK, DE Ulm UK, DE Hamburg-Eppendorf UK, DK Aarhus DNU, DK Copenhagen Rigshospitalet, ES Barcelona Sant Joan, ES Barcelona Vall d’Hebron, ES Madrid La Paz, ES Barcelona Fundació Puigvert. FI Helsinki HUS. FR Paris Necker, FR Paris Robert-Debré, IT Bergamo Papa Giovanni XXIII, IT Bologna AOU, IT Milan Policlinico, LT Vilnius SK, LV Riga BKUS, NL Rotterdam Erasmus, NL Nijmegen Radboudumc, NL Utrecht UMC, PL Gdansk MUG, PL Krakow USD, SE Stockholm Karolinska, SE Gothenburg Sahlgrenska, SE Lund SUS, SE Uppsala Akademiska
Additional Resources	Posterior urethral valves. Disease InfoSearch page and Genetic and Rare Diseases Information Center page.

EA 1.6 Posterior hypospadias

Definition	Hypospadias is a congenital abnormality of the male external genitalia where the urethral opening is located on the underside of the penis instead of the tip. Posterior hypospadias specifically refers to a form of hypospadias where the urethral opening is located closer to the scrotum, closer to the base of the penis, or in the perineum (the area between the scrotum and anus). In posterior hypospadias, the degree of abnormality is more severe than in other forms of hypospadias, and surgical correction may be necessary to improve urination, sexual function, and cosmetic appearance. The condition is typically diagnosed soon after birth and may be associated with other birth defects or genetic syndromes.
Conditions & Codes	Non-syndromic posterior hypospadias: ORPHAcode 95706 / ICD-10 Codes Q54.0, Q54.1, Q54.2, Q54.3, Q54.4, Q54.8, Q54.9
EAC & Vice-EAC	Expertise Area Coordinator: Magdalena Fossum, DK Copenhagen Rigshospitalet Vice-EAC: Alessandro Morlacco, IT Padua AOU
Healthcare Providers	AT Linz Ordensklinikum, BE Antwerp UZ, BE Leuven UZ, CZ Prague VFN, DE Mannheim UK, DE Regensburg UK, DE Tübingen UK, DE Ulm UK, DE Hamburg-Eppendorf UK, DK Aarhus DNU, DK Copenhagen Rigshospitalet, ES Barcelona Sant Joan, ES Barcelona Vall d’Hebron, ES Madrid La Paz, ES Barcelona Fundació Puigvert, FI Helsinki HUS, FR Paris Robert-Debré, IT Bergamo Papa Giovanni XXIII, IT Padua AOU, IT Bologna AOU, IT Milan Policlinico, IT Rome Bambino Gesu, LT Vilnius SK, LV Riga BKUS, NL Nijmegen Radboudumc, NL Utrecht UMC, PL Gdansk MUG, PL Krakow USD, SE Stockholm Karolinska, SE Gothenburg Sahlgrenska, SE Lund SUS, SE Uppsala Akademiska
Additional Resources	Hypospadias. Disease InfoSearch page and Genetic and Rare Diseases Information Center page.

EA 1.7 Urorectal/anorectal malformations

Definition	Urorectal/anorectal malformations refer to a group of congenital anomalies affecting the development of the urinary and/or digestive systems, resulting in abnormalities in the way urine and faeces are eliminated from the body. These malformations can involve various parts of the urinary and/or digestive tract, such as the bladder, urethra, genital organs, rectum, and anus. Urorectal/anorectal malformations are typically diagnosed soon after birth and may require surgical intervention to correct. The severity and specific type of urorectal malformation can vary widely, and some cases may be associated with other birth defects or genetic syndromes.
Conditions & Codes	Non-syndromic anorectal malformation: ORPHAcode 557 / ICD-10 Code Q42.0, Q42.1, Q42.2, Q42.3 with perineal fistula: ORPHAcode 600952 with rectourethral fistula, unknown type: ORPHAcode 600961 with rectourethral fistula, bulbar type: ORPHAcode 600966 with rectourethral fistula, prostatic type: ORPHAcode 600975 with rectovesical fistula: ORPHAcode 600984 with vestibular fistula: ORPHAcode 600993 without fistula: ORPHAcode 601002 with anal stenosis: ORPHAcode 601008 with pouch colon: ORPHAcode 601013 with rectal atresia: ORPHAcode 601018 with rectal stenosis: ORPHAcode 601023 with rectovaginal fistula: ORPHAcode 601028 with H-type fistula: ORPHAcode 601033 Non-syndromic cloacal malformation: ORPHAcode 600998 Anal fistula: ORPHAcode 228113 / ICD-10 Code K60.3 VACTERL/VATER association: ORPHAcode 887 / ICD-10 Code Q87.2
EAC, Vice-EAC & ePAGs	Expertise Area Coordinator: Ivo de Blaauw, NL Nijmegen Radboudumc Vice-EAC: Martin Lacher, DE Leipzig UK Patient Representatives: Dalia Aminoff, AIMAR, Nicole Schwarzer, SoMA e.V., Kate Tyler, TOFS
Healthcare Providers	BE Antwerp UZ, BE Leuven UZ, DE Berlin Charité, DE Munich LMUK, DE Bremen-Mitte Klinik, DE Leipzig UK, DE Mannheim UK, DE Aachen UK, DK Aarhus DNU, DK Copenhagen Rigshospitalet, ES Barcelona Sant Joan, ES Madrid La Paz, ES Barcelona Fundació Puigvert, FI Helsinki HUS, FR Paris Necker, IT Bergamo Papa Giovanni XXIII, IT Padua AOU, IT Bologna AOU, IT Milan Policlinico, IT Rome Bambino Gesu, LT Vilnius SK, LV Riga BKUS, NL Amsterdam AMC, NL Groningen UMC, NL Rotterdam Erasmus, NL Nijmegen Radboudumc, PL Gdansk MUG, PL Krakow USD, SE Stockholm Karolinska, SE Gothenburg Sahlgrenska, SE Lund SUS
Additional Resources	Anorectal Malformations. Disease InfoSearch page and Genetic and Rare Diseases Information Center page. ARM-Net. The ARM-Net Consortium is a group of professionals and patient representatives that aim to exchange data and knowledge to improve clinical care and to perform research on congenital anorectal malformations. Sexual Support for Anorectal Malformations & Hirschsprung’s Disease. A website available in English and Dutch, developed in close collaboration with patients and specialist practitioners in the Netherlands for patients, their parents, healthcare professionals, and other relations. TOFS. Working towards a world in which those born with OA/TOF and VACTERL live long and healthy lives, unconstrained by the impact of being born with these conditions. Joe’s IA/ARM Story. Joe shares his story of being an adult born with IA/ARM. (Spring 2023 edition of TOFS Chew Magazine) Shaun’s OA/TOF Story. Shaun shares his story of being an adult born with OA/TOF and VACTERL symptoms. (+ article in Spring 2023 edition of TOFS Chew Magazine) Max’s Trust Annual Conference – Report by Kate Tyler (Winter 2022 edition of TOFS Chew Magazine) VACTERL/VATER association. Disease InfoSearch page and Genetic and Rare Diseases Information Center page.
Patient Journey (Click here to download as a pdf)	ARM-Patient-Journey

General Resources

EAU Paediatric Urology Guidelines. The European Association of Urology (EAU) Paediatric Urology Guidelines Panel has prepared these guidelines with the aim of increasing the quality of care for children with urological conditions.
EAU Congenital Malformation in the Urinary Tract Patient Information. The European Association of Urology (EAU) Patient Office provides reliable patient information on urology conditions and urology health.
ESPU Parent and Patient Information System. An online e-book containing information on the most common genitourinary disorders in children.
Pull-thru Network, Inc. The Pull-thru Network is an international volunteer-based organisation dedicated to providing education, information, support and advocacy for those individuals, and the families of those individuals, who are affected by any congenital anorectal, colorectal or urogenital disorder and any of the variety of related diagnoses.