Can Vesicoureteral Reflux be Inherited?

The most common form of urinary tract pathology in the pediatric population is vesicoureteral reflux (VUR). This term denotes the backward flow of urine from the bladder to the ureters, and may be primary or secondary. It is graded on a scale from 1-5, with 5 being the most severe. Signs and symptoms of VUR may vary depending on the age of the child.

Very young infants may be irritable and show failure to thrive, accompanied by lethargy, anorexia, vomiting, diarrhea and fever. Older children may have symptoms of urinary tract infection (UTI) such as burning pain during micturition, increased frequency or urgency, and vague abdominal pain as well as fever.

Diagnosis is based upon suitable tests, including urinalysis, together with imaging and urodynamic studies. Urinalysis is imperative for guiding treatment of the UTI, whereas imaging studies are vital to detect any urinary tract structural abnormalities, and urodynamic analyses are necessary to study how well the urinary system functions. These investigations are important for determining the choice of therapeutic avenue. In mild cases, surveillance alone may be opted for, since VUR tends to resolve spontaneously as the child grows. In other cases, timely medical and/ or surgical therapy may be necessary to prevent serious complications.

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During embryonic development, the formation of an ectopic ureteric bud is implicated in VUR pathogenesis. This causes a short ureter to form, which in turn leads to a failure of the distal ureteric valve that should have formed at the ureterovesical junction (UVJ). There are many genes responsible for the formation of the ureteric buds and the rest of the urinary system, in particular the kidneys and ureters. Mutations in these genes give rise to many congenital syndromes that may present with VUR as one feature.

Familial Inheritance of VUR

A genetic component to VUR is strongly suggested by studies that highlight the well-recognized recurrence of the condition in certain families. Studies show that siblings of affected children have an increased risk of developing VUR themselves. These studies place the increase in risk anywhere between 26% and 50%. However, the risk is difficult to predict, because of the spontaneous resolution that occurs as affected children grow.

Studies show that up to half of all children affected with VUR are from a family with a positive history for VUR. Furthermore, identical and fraternal twins develop concordant primary VUR at a rate of 80% and 35%, respectively. The mode of inheritance of VUR has varying patterns as shown in different studies. Some studies found an autosomal dominant mode, while others identified an autosomal recessive pattern. There are also studies that propose it may be X-linked and there are still others that suggest it is polygenic.

The potential link between VUR and genetic inheritance is still unclear, especially considering that no causative gene has yet been implicated. There are several studies aimed at identifying the culprit gene, but no gene yet studied fits the bill. More research is therefore essential for the elucidation of VUR and its genetic basis. This is of particular importance, because a greater understanding of the heritability of the condition may lead to novel ways of treating those children affected or of preventing its complications.


Further Reading

Last Updated: Feb 27, 2019

Dr. Damien Jonas Wilson

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Dr. Damien Jonas Wilson

Dr. Damien Jonas Wilson is a medical doctor from St. Martin in the Caribbean. He was awarded his Medical Degree (MD) from the University of Zagreb Teaching Hospital. His training in general medicine and surgery compliments his degree in biomolecular engineering (BASc.Eng.) from Utrecht, the Netherlands. During this degree, he completed a dissertation in the field of oncology at the Harvard Medical School/ Massachusetts General Hospital. Dr. Wilson currently works in the UK as a medical practitioner.


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