About 10 percent of kids born with kidney defects have large alterations in their genomes known to be linked with neurodevelopmental delay and mental illness, a new study by Columbia University Medical Center (CUMC) researchers has shown.
The study was published today in the online edition of the American Journal of Human Genetics.
Congenital defects of the kidney and urinary tract account for nearly 25 percent of all birth defects in the US and are present in about 1 in every 200 births. Eventually, an evaluation for genomic alterations will be part of the standard clinical workup. Patients with congenital kidney disease—who are currently lumped into one category—will be placed in subgroups based on their genetic mutations and receive a more precise diagnosis.
"This changes the way we should handle these kids," said 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."
"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," he said. "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."
The current study was the result of a large collaborative effort of CUMC and other medical centers in the US, Italy, Poland, Croatia, Macedonia, and the Czech Republic. It was led by Dr. Gharavi and his colleague Simone Sanna-Cherchi, MD, an associate research scientist in CUMC's Department of Medicine.
Until now, no studies have linked congenital kidney disease with neurodevelopmental disorders.
"If you talk to clinicians, they tell you that some of these kids behave differently," Dr. Sanna-Cherchi said. "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."
About 20 percent of kidney defects caused by large DNA mutations
The mutations discovered by Drs. Gharavi and Sanna-Cherchi and their colleagues belong to a class of mutations called copy number variations (CNVs). CNVs are extra copies or deletions of DNA just large enough to contain several genes. When CNVs are present, the "dose" of the affected genes is either lower or higher than normal, potentially leading to a health disorder.