New mutation is linked with rare juvenile Batten disease: Case report
Boy in Gaza was only 'fifth known case' of CLN14, researchers said
A new mutation in the KCTD7 gene was identified in a boy as the cause of CLN14 disease, a rare form of infantile-onset Batten disease.
The report, “A novel pathogenic variant in the KCTD7 gene in a patient with neuronal ceroid lipofuscinosis (CLN14): a case report and review of the literature,” was published in BMC Neurology. The study’s researchers called the boy’s case only the “fifth known case of CLN14 in the literature.”
Batten disease refers to a group of inherited, rare neurological conditions marked by the toxic buildup of lipofuscin inside cells, which is particularly damaging to the brain. The disease is caused by a genetic defect, or mutation, in one of 14 genes — CLN1 through CLN14 — that result in several different types of it.
CLN14 disease is an extremely rare type of Batten disease, with only four cases described in the literature. It’s caused by mutations affecting both alleles, or gene copies, of the KCTD7 gene, which provides instructions for producing a protein widely found in the brain where it regulates the flow of potassium across cell membranes.
CLN14 is characterized by myoclonic seizures, that is, brief, uncontrollable jerks of a muscle, before age 2 and vision loss.
New gene mutation
Here, researchers at the Islamic University of Gaza, in the Gaza Strip, described what they called the “fifth case in the literature with the CLN14 subtype” due to a novel mutation in the KCTD7 gene.
The boy was born from first-degree cousins through a normal vaginal delivery. However, at 9 months he wasn’t able to sit unsupported and by his first birthday he began having myoclonic seizures, with abnormal jerks in the extremities, trunk, and eyes.
His physical skills, such as sitting up and crawling, also started to regress, and were accompanied by a decline in verbal communication and social interactions, and by facial changes, such as low-set ears. A neurological exam revealed low muscle tone and brisk reflexes. Blood work was normal, as were a brain CT scan and an MRI scan.
When the boy was 18 months, he had his first episode of generalized tonic-clonic seizures, which involve both stiffening and twitching phases of muscle activity. His motor and cognitive development also regressed further, as he couldn’t maintain balance and was unable to recognize familiar faces. His social interactions were impaired.
An MRI scan showed signs of mild brain wasting. An electroencephalogram, which measures the brain’s electrical activity, showed signs of a higher seizure risk. The generalized tonic-clonic seizures became more frequent and didn’t respond to treatment.
Genetic testing showed a new mutation in KCTD7, establishing a diagnosis of CLN14 disease. Both parents were carriers of the mutation in their CLN14 gene copies.
By his second birthday, the boy continued to have generalized tonic-clonic seizures despite intensive treatment with anti-seizure medications. Neurological exams showed worsening muscle tone and reflexes. He died at age 3 from status epilepticus, which is marked by either a single seizure that lasts longer than five minutes, or many seizures occurring close together without the patient recovering consciousness between them, and pneumonia.
“Improving accessibility and affordability of genetic testing will likely uncover more [Batten disease] cases and further expand the disease’s genotypic and phenotypic [gene profile and observable characteristics] spectrum,” the researchers wrote.
About the Author
