Mutations present in children born with kidney defects are known to cause neurodevelopmental delay or mental illness, according to new research appearing in the American Journal of Human Genetics.

Around 10 percent of kids with kidney defects have these mutations in their genomes, also known to be associated with mental illness and neurodevelopmental delay.

Congenital urinary tract and kidney defects make up about 25 percent of all birth defects in the United States and are found in one in every 200 births.

At last, an analysis for genomic alterations will be included in standard clinical workup. Patients who have congenital kidney disorder, presently included in one group, will be put into subcategories according to their genetic mutations, resulting in a more specific diagnosis.

Kidney specialist Ali Gharavi, MD, associate professor of medicine at CUMC, associate director of the Division of Nephrology, and an internist and nephrologist at NewYork-Presbyterian Hospital says:

“If a physician sees a child with a kidney malformation, that is a warning sign that the child has a genomic disorder that should be looked at immediately because of the risk of neurodevelopmental delay or mental illness later in life. This is a major opportunity for personalizing medical care. As we learn which therapies work best for each subgroup, the underlying genetic defect of the patient will dictate what approach to take.”

This study was a broad collaboration of CUMC and other medical centers worldwide. Up until this point, no studies have successfully connected congenital kidney disease with neurodevelopmental disorders.

Simone Sanna-Cherchi, MD, an associate research scientist in CUMC’s Department of Medicine explains:

“If you talk to clinicians, they tell you that some of these kids behave differently. There has been a general assumption, though, that behavioral or cognitive issues in children with chronic illnesses such as kidney disease stem from the child’s difficulty in coping with the illness. Our study suggests that in some cases, neurodevelopmental issues may be attributable to an underlying genomic disorder, not the kidney disease.”

Nearly 20 percent of kidney defects come from big DNA mutations. The mutations identified by Drs. Gharavi and Sanna-Cherchi and their team, are in a class of mutations known as copy number variations (CNVs).

CNVs are DNA surplus copies or deletions only big enough to contain several genes. When CNVs are there, the “dose” of the impacted genes is either lower or higher than normal, possibly resulting in a health disorder.

Before successful techniques for identifying CNVs were developed, scientists believed that CNVs lead only a few health disorders. Now, tens of thousands of different CNVs have been found and linked to many disorders such as autism, Parkinson’s disease, and schizophrenia.

In order to examine CNVs’ involvement in congenital kidney defects, the researchers scanned the genomes of 522 participants with small and malformed kidneys. Around 17 percent of the patients had a CNV that looked to play a part in their kidney disorder.

In previous research of children with already discovered CNVs, many of the CNVs had been connected to developmental delays or mental illness. In this study, one in ten children had a CNV connected to mental illness or developmental delays.

Although they are uncertain why kidney malformations and neurodevelopment are occasionally connected, it is conceivable that the same genes that take part in kidney development are also involved in brain development, the authors suggest.

Congenital kidney disease could include hundreds of different genes. The exploration for CNVs in congenital kidney disease also shows that the genes contributing to the disease are much greater in number than predicted.

Dr. Gharavi said, “We thought we were going to find a few CNVs shared by many patients, but instead we found that virtually every patient with a CNV has a unique one. Virtually every patient has a unique condition that could not be diagnosed by a standard clinical evaluation.”

Drawing from their conclusions, the authors hypothesize that there could be hundreds of different genes that can cause a congenital kidney malformation.

Written by Kelly Fitzgerald