Congenital urogenital malformations

Paediatric urology, an orphan specialty

Enuresis, hypospadias, bladder exstrophy, renal ectasia, lithiasis, hydronephrosis ... Greek and Latin terminology for a wide range of paediatric urogenital anomalies and disorders, which are mostly congenital and orphan diseases. The Paediatric Urology Unit of the Fundació Puigvert is a national benchmark in solving these problems.

Bladder exstrophy or open bladder at skin level, with continuous urine leakage, is a congenital anomaly that occurs in one out of every 50,000 births, twice as often in men as in women. It can coexist with epispadias, when the urethra – the tube through which urine from the bladder passes – ends in an opening in the upper part or dorsum of the penis (like an open book) and, in women, when the urethra develops in positions that are higher than usual, i.e. with a bifid clitoris, a shorter vagina and a more anterior location than normal.

Bladder exstrophy, which affects one in every 50,000 births, is one of the congenital genitourinary malformations treated by specialists at the Fundació Puigvert. "We treat more than 1,000 children a year with urogenital diseases. Whenever possible, we perform minimally invasive treatments, such as robotic surgery, pioneering this technique in Spain, or endourological treatment," says Anna Bujons, head of the Paediatric Urology Unit.

"As a monographic centre specialising in Nephrology and Urology, most of the conditions we see in our Unit are congenital disorders of the kidney and urinary tract; we encounter the so-called rare or orphan genitourinary diseases, as well as kidney stones in children, enuresis or other conditions related to the male and female urinary or genital system."

Below are some of these disorders:

• vesicoureteral reflux
• posterior urethral valves
• primary obstructive megaureter
• spina bifida, alterations of sex differentiation
• incontinence, renal ectasia, hydronephrosis
• pyeloureteral junction syndrome
• urethral stricture, renal cysts
• urinary tract infections
• anorectal malformations
• hypospadias

etc.

We are a benchmark centre for the comprehensive care of children suffering from kidney stones (renal lithiasis), who are monitored until adulthood. They require multidisciplinary care for the prevention and recurrence of stones and complications, as well as minimally invasive treatment.

We treat more than 250 paediatric patients a year with kidney stones due to rare metabolic or inherited diseases and we provide comprehensive monitoring (from birth to adulthood) for more than 150 patients with bladder exstrophy from all over the country and more than 200 children with proximal and complex hypospadias.

Urogenital variety

Congenital, structural or functional disorders, such as spina bifida, Down's syndrome or oesophageal atresia, are anatomical, metabolic or genetic alterations that occur in the intrauterine stage due to environmental or genetic factors, deficiencies in nutrient uptake, infections or the consumption of harmful substances, from alcohol to certain drugs. They occur in 3% of births and account for more than 20% of all infant deaths.

The most common and lethal are congenital heart disease (300,000 deaths per year worldwide) and neural tube defects (65,000 deaths).

Congenital anomalies of the urogenital tract (CAKUT) are a group of malformations ranging from mild to life-threatening (approximately 30% of all malformations diagnosed before birth). They affect the kidney, ureters, bladder, urethra, penis, testes and female genitalia (one or more parts) and occur during foetal development of the urinary/genital system.

They are often concomitant to other birth defects outside the kidney and collecting ducts (ureters/bladder/urethra). They are a major cause of kidney failure and transplantation. While some do not cause symptoms and do not require treatment, others need to be treated medically and surgically.

European and national accreditation

In 2022, the European Union approved the incorporation of the Fundació Puigvert into eUROGEN, the European Reference Network for Rare Urogenital Diseases and Complex Conditions requiring highly specialised surgery, and to ERKnet, the European Rare Kidney Diseases Reference Network (ERKnet). This membership has been possible thanks to the experience and supra-specialisation in congenital genitourinary malformations and rare urological tumours, as well as inherited and glomerular kidney diseases.

The Fundació Puigvert thus becomes the only centre in Spain accredited in the network's three work areas. "Being a part of it," Dr Anna Bujons explains, "allows us to work with the best professionals from different fields, hence creating multidisciplinary teams to share our knowledge and develop clinical practice guidelines or support tools for decision-making in highly specific cases."

Moreover, in 2018 the institution had already been designated as a national reference unit (CSUR) by the Ministry of Health for the exstrophy-epispadias complex, i.e. an integrated unit of the Hospital de Sant Pau.

The CSURs are Reference Centres, Services or Units of the National Health System. This category is granted only to healthcare centres which provide care for certain diseases or groups of diseases that are considered rare and which require a high level of specialisation or cutting-edge technology for their prevention, diagnosis or treatment.

It also requires knowledge, experience, a sufficiently high turnaround in applying the technique, technology or procedure being accredited, as well as optimal performance indicators.

On a regional level, the Fundació Puigvert is accredited as an XUEC centre, a network of clinical specialisation units (Xarxa Unitats Especialització Clínica), for the diagnosis and treatment of orphan paediatric kidney diseases.

Exstrophies and hypospadias

Dr Bujons explains that the exstrophy-epispadias complex (EEC) "represents a whole spectrum of genitourinary malformations with different severity levels. Depending on the severity, it can affect the urinary system, locomotor system, pelvis, pelvic floor, abdominal wall, genitals and sometimes the spine and anus."

According to the Ministry of Health, the CSURs of the National Health System must cover the whole of Spain and attend to all patients on equal terms.

Furthermore, they must provide multidisciplinary care: healthcare, support for diagnostic confirmation, definition of therapeutic and follow-up strategies and consultancy for the clinical units that treat these patients.

On the other hand, they must guarantee continuity of care at different stages of the patient's life (child-adult) and between care levels, and undertake to assess the results and provide training to other professionals.

Another disorder which is most frequently treated by Dr Bujons' team is hypospadias, a birth defect in which the urethra, the tube through which urine exits, has not formed properly and whose end is in a different place than usual, such as at the base of the penis or above the testicles.

It is associated with penile curvature and foreskin defects.

It occurs in 18 out of every 10,000 births and is caused by several factors: genetics, hormonal disorders, environmental factors, such as pesticides, low birth weight, very young or older first-time mothers. Some are diagnosed in prenatal ultrasounds, but they are generally observed during the physical examination of newborns.

Sex anomalies

Less common – one in every 2,000 live newborns – are disorders of sex development, congenital conditions involving abnormal development of chromosomal (genetic), gonadal (ovarian or testicular) or anatomical (genital) sex. This alteration is almost always caused by genetic issues, with up to 40 genes known to be involved in its occurrence, apart from the maternal or environmental factors that can cause it.

Diagnosis can be performed prenatally (in ultrasounds or genetic tests), when the baby is born by observing alterations in the genitalia and during puberty due to the absence of menstruation or a delay in the physical changes that kickstart adolescence. The karyotype test – a blood test that establishes the baby's genetic sex –, hormone analyses and abdominal ultrasounds determine the baby's internal genital organs.

Its care requires a multidisciplinary team – geneticists, neonatologists, endocrinologists, paediatric urologists, gynaecologists, psychologists, ethicists and social workers –, as this disease has not only obvious physical alterations, but also social, family and ethical implications that need to be considered.

For correct gender assignment, parents receive advice from the whole team. If hormonal reasons for the alterations are identified, the relevant medical treatment will be given. As for surgical management, the current trend is not to perform mutilating surgeries, but only those strictly necessary until the patient can participate in the decision-making process.

Enuresis and urinary incontinence

One of the most common enquiries at the paediatric urology unit of the Fundació Puigvert is linked to functional voiding disorders and nocturnal bedwetting or enuresis. Enuresis affects 16% of 5-year-olds, 10% of 6-year-olds and 7.5% of 10-year-olds in Spain. After the age of 15, the problem persists in 1 to 3% of the population.

Involuntary urination is more frequent in boys from the age of five and during sleep. It is often underdiagnosed, but with early detection, appropriate treatment and motivation, it is relatively easy to solve.

 "Bedwetting at an age when a child should have voluntary control over urination is not normal and does not always resolve spontaneously," says Dr Bujons.

"Early diagnosis and choosing the right treatment are key to prevent the problem from developing into more serious future implications."

The risk of bedwetting is 5 to 7 times higher among children with an enuretic parent and about eleven times higher if both parents were enuretic, i.e. there is a clear inherited factor. However, it may be multifactorial, and its causes need to be researched.

European training centre

The Fundació Puigvert has been certified by the European Academy of Paediatric Urology (EBPU) to carry out the European specialisation training programme in paediatric urology. The programme is carried out under the direction of Dr Bujons and lasts two years. In Spain, there are only three centres with this accreditation.

Last year, the Paediatric Urology Unit of the Fundació Puigvert joined the list of services accredited by the European Board of Urology (EBU) for training specialists and researchers in the different urological subspecialties. The EBU has also granted the same accreditation for the pathologies of urothelial, prostate and renal cancer, renal transplantation, kidney stones and female urology as well as incontinence, which are taken care of at the Fundació Puigvert.

Research and innovation

The paediatric urology unit also undertakes research, development and innovation activities. They are key for the unit's development and for generating and incorporating new knowledge to address the health challenges of paediatric patients.

Together with the growing progress in genetic diagnosis research, which has advanced the detection of many pathologies of this kind,

Dr Bujons mentions her team's participation in tissue engineering projects applied to neobladders and neourethras, using stem cells with the aim of advancing and applying them to patients with bladder or urethral malformations or diseases.

What is more, the technological advances and innovations that have been incorporated, such as robots in paediatric urology, have allowed our patients to access a groundbreaking and cutting-edge service with the aim of obtaining the highest success rate in surgical procedures.

The new development of high-power lasers and smaller instruments is highly effective and safer for patients.

The ultimate aim is to be able to tackle any paediatric urogenital issue through careful reconstruction, minimum surgical invasiveness and maximum tissue preservation, which the experts at the Fundació Puigvert are closer to achieving on a daily basis.

 [BTA1]- Member of the paediatric board group of the European Association of Urology (EWPU-EAU)

- Member of the educational committee of the European Society of Paediatric Urology (ESPU)

- Member of the board of the Ibero-American Association of Paediatric Urology

- Member of the board of the endourology section – ESUT of the European Association of Urology (EAU)

- Member of the Association of European Academic Urologists (AAEU)