New QRICH1 Gene Change Linked To Ververi-Brady Syndrome

What was studied

This paper described one infant boy with Ververi-Brady syndrome who presented with infantile epileptic spasms syndrome. He was 5 months and 22 days old when he was admitted to a children's hospital after 10 days of intermittent nodding episodes. The doctors reviewed his clinical features, which included facial dysmorphism, global developmental delay, and epileptic spasms.

The team also looked for a genetic cause by testing the child and both parents with trio whole-exome sequencing, then confirmed the finding with Sanger sequencing. They also reviewed earlier published reports about QRICH1 gene variants and Ververi-Brady syndrome to compare this child's symptoms with other known cases.

What they found

The study identified a novel de novo pathogenic variant in the QRICH1 gene in this child. "De novo" means the variant was not found in either parent and appears to have arisen in the child.

In this case, treatment with ACTH and vigabatrin was followed by seizure freedom, EEG improvement, and developmental gains. In the authors' literature review of 46 patients total, common features reported in QRICH1-related Ververi-Brady syndrome included developmental delay, hypotonia, facial dysmorphism, autism spectrum disorder, epilepsy, and scoliosis.

Limits of the evidence

This was mainly a single case report, so it cannot show what usually happens for all children with QRICH1-related Ververi-Brady syndrome or establish that the treatment will work the same way in others. The improvement seen after ACTH and vigabatrin was in one child only.

The literature review summarized previously reported cases, but those reports may differ in quality and detail. Because the condition is rare and only a limited number of patients have been described, there is still uncertainty about the full range of symptoms, long-term outcomes, and treatment responses for seizures in this syndrome.

For families and caregivers

For families, this report suggests that QRICH1-related Ververi-Brady syndrome can occur with infantile epileptic spasms syndrome, in addition to developmental and physical features. It also shows that genetic testing may help identify an explanation for a baby's spasms and developmental delay.

The report may offer some cautious hope because the child's seizures stopped after treatment and his development improved, but this is only one case. Families should not assume the same course for every child with this rare condition.

What to watch next

More reported children with QRICH1-related epileptic spasms and longer follow-up on seizure control and development would help clarify the clinical spectrum and outcomes.

Terms in this summary

Ververi-Brady syndrome

A rare genetic condition linked to variants in the QRICH1 gene, often involving developmental delay and other physical or neurologic features.

infantile epileptic spasms syndrome

An epilepsy syndrome in babies that causes repeated spasms and is typically associated with abnormal EEG findings.

de novo

A genetic change that is new in the child and was not found in either parent.

trio whole-exome sequencing

A genetic test that looks at many genes in a child and both parents to help find the cause of a condition.

frameshift variant

A type of DNA change that shifts how the gene's code is read, often leading to an altered protein.

ACTH

A medicine sometimes used to treat infantile spasms.

vigabatrin

An anti-seizure medicine often used for infantile spasms.

EEG

A test that records the brain's electrical activity.