Agneta Nordenskjöld Group

Two percent of all newborns have a congenital malformation. The parents often ask why this has happened, how it is treated, if there is a recurrence risk and what will happen in the future. We have over the years studied several different congenital malformations mainly different disorders of sex development, especially hypospadias and congenital adrenal hypertrophy (CAH), with molecular genetic methods, clinical follow-up and national register studies.

The main focus now concerns bladder exstrophy when the child is born with an open urinary bladder. This happens to around three children per year in Sweden. They are operated early with closure of the bladder and pelvis, and will need life-long clinical follow-up. There is evidence for a genetic cause since both familial cases exist, usually sibs and parent-child-pairs, chromosome aberrations are described in association with bladder exstrophy and the concordance rate is higher in monozygotic twins than in dizygotic ones. There is a lack of long-term follow-up studies, apart from in young adults. There is a high risk for these patients to develop urinary bladder cancer at a younger age than expected in the population.

The aim is to understand the molecular background, to explore the long-term consequences of being born with bladder exstrophy including personal experiences and finally to further study the urinary bladder cancer risk.

If a molecular diagnosis is identified, the information about the child to the parents can be improved concerning further follow-up, prognosis and recurrence risk in the family. The long-term-follow up of adults will also result in better information and better health care. Thus, the results can easily directly be implemented in clinical practice.

• Molecular studies on DNA from patients, and trios if possible, by performing chromosomal micro array and whole genome sequencing.
• Clinical follow-up of adults born with bladder exstrophy. PI ass. Prof. Gundela Holmdahl.
• In-depth interviews with adults born with bladder exstrophy.
• Register based studies on a national basis in order to identify different aspects of living with these diagnoses.

Agneta Nordenskjöld, MD, professor pediatric surgery, KI, agneta.nordenskjold@ki.se

Lottie Phillips, MD, lottie.phillips@ki.se

Samara Arkani, MD, samara.arkani@ki.se

Research Council, Stiftelsen Frimurare Barnhuset i Stockholm, Birgitta och Carl-Axel Rydbecks forskningsanslag för pediatrisk forskning, Karolinska institutet, ALF-medel Region Stockholm.