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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.

ORPHAcodes & ICD-10 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

• Expertise Area Coordinator: Katja Wolffenbuttel, Erasmus University Medical Center, Rotterdam (NL)
• Vice-Expertise Area Coordinator: Verena Ellerkamp, Universitätsklinikum Tübingen (DE)

ePAG Advocate / Patient Representative

• Claire Harkin, Klinefelter’s Syndrome Association (UK)

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. 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, which include:

1. Pediatric Decision Making and Differences of Sex Development: A Societies for Pediatric Urology and American Urological Association Joint Position Statement
2. American Medical Association Code of Ethics policy for Pediatric Decision Making
3. Societies for Pediatric Urology and the European Society for Pediatric Urology Joint Consensus Statement on the Management of Differences in Sexual Development

[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.]

Turner Syndrome. Disease InfoSearch page and Genetic and Rare Diseases Information Center page.

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.

ORPHAcodes & ICD-10 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

• Expertise Area Coordinator: Alaa El Ghoneimi, Hôpital Universitaire Robert-Debré, Paris (FR)
• Vice-Expertise Area Coordinator: Gundela Holmdahl, Karolinska Universitetssjukhuset, Stockholm (SE)

ePAG Advocate / Patient Representative

• Steven Leusenkamp, Patiëntenvereniging voor Blaasextrofie Nederland (NL)

Patient Journey

Click here to download as PDF

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.

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.

ORPHAcodes & ICD-10 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: (position open)
• Vice-Expertise Area Coordinator: (position open)

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.

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.

ORPHAcodes & ICD-10 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, Ospedale Pediatricio Bambino Gesù, Rome (IT)
• Vice-Expertise Area Coordinator: Kate Abrahamsson, Sahlgrenska Universitetssjukhuset, Göteborg (SE)

Patient Journey

Click here to download as PDF.

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.

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.

ORPHAcodes & ICD-10 Codes

• Congenital posterior urethral valves:
  ORPHAcode 93110 / ICD-10 Code Q64.2

EAC & Vice-EAC

• Expertise Area Coordinator: Yazan Rawashdeh, Aarhus Universitetshospital (DK)
• Vice-Expertise Area Coordinator: Rafal Chrzan, Uniwersytecki Szpital Dziecięcy w Krakowie (PL)

Additional Resources

Posterior urethral valves. Disease InfoSearch page and Genetic and Rare Diseases Information Center page.

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.

ORPHAcodes & ICD-10 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, Rigshospitalet, Copenhagen (DK)
• Vice-Expertise Area Coordinator: Alessandro Morlacco, Azienda Ospedaliera-Università di Padova (IT)

Additional Resources

Hypospadias. Disease InfoSearch page and Genetic and Rare Diseases Information Center page.

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.

ORPHAcodes & ICD-10 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

• Expertise Area Coordinator: Ivo de Blaauw, Radboud University Medical Center, Nijmegen (NL)
• Vice-Expertise Area Coordinator: Martin Lacher, Universitätsklinikum Leipzig (DE)

ePAG Advocates / Patient Representatives

• Dalia Aminoff, Associazione Italiana per le Malformazioni Anorettali (IT)
• Nicole Schwarzer, Selbsthilfeorganisation für Menschen mit Anorektalfehlbildungen eV, SoMA e.V. (DE)
• Kate Tyler, TOFS (UK)

Patient Journey

Click here to download as pdf

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.

VACTERL/VATER association. Disease InfoSearch page and Genetic and Rare Diseases Information Center page.