Genetic Testing Found Answers For Some Adults With DEE

What was studied

This study looked at copy number variants, also called CNVs, in 219 adults with developmental and epileptic encephalopathy (DEE) who still did not have a diagnosis. The group included 104 males and 115 females. All underwent array-based comparative genomic hybridization/single nucleotide polymorphism arrays as adults.

The researchers wanted to examine the role of CNVs in the cause of DEE in this adult cohort and help define the most appropriate diagnostic approach in this population, especially because some other genetic tests may be harder to do in adults or may cost more.

What they found

The chromosome array testing identified a causative CNV in 18 of 219 patients, which is 8.2%. Most of these were deletions, and a smaller number were duplications or triplications. Thirteen were responsible for known deletion or microduplication syndromes, and four were deletions involving haploinsufficient genes associated with epilepsy or neurodevelopmental disorders.

The mean age at CMA diagnosis was about 32 years, and the paper reports an average diagnostic delay of about 24 years. Another 46 patients later received a molecular diagnosis through other approaches. The authors report that CMA enabled a genetic diagnosis in 8.2% of these adult DEE patients, especially in those with dysmorphisms, and that the yield rose to 10.4% when excluding patients diagnosed using other methods. In 66.7% of solved cases, the diagnosis had direct implications.

Limits of the evidence

This was not a comparison trial, so it cannot show that this is the best testing strategy for every adult with DEE. The study only included adults who were still undiagnosed, so the results may not apply to all people with DEE. The abstract does not explain in detail what the direct implications were.

Also, most patients did not get a diagnosis from this test alone. Some patients were diagnosed later by other methods, which shows that chromosomal microarray does not find every genetic cause. The abstract does not give full details about symptoms, prior testing, or how broadly the findings apply across different health systems.

For families and caregivers

For families, this study suggests that chromosomal microarray testing can still find a genetic cause in some adults with developmental and epileptic encephalopathy, even after many years without answers. The abstract reports that it was especially helpful in patients with dysmorphisms.

A genetic diagnosis may help explain the condition and sometimes have direct clinical implications. But this study also shows that many people will still need other kinds of genetic testing, and some may remain without a clear answer.

What to watch next

Useful next studies would compare chromosomal microarray directly with exome or genome testing in adults with DEE and describe more clearly how often results have direct clinical implications.

Terms in this summary

developmental and epileptic encephalopathy

A group of severe epilepsy conditions in which seizures and the underlying brain disorder can affect development and daily functioning.

copy number variant

A missing or extra piece of DNA that can sometimes cause health or developmental problems.

chromosomal microarray

A lab test that looks for missing or extra pieces of chromosomes across the genome.

deletion

A type of genetic change where a piece of DNA is missing.

duplication

A type of genetic change where an extra copy of a piece of DNA is present.

triplication

A type of genetic change where there are three copies of a piece of DNA instead of the usual number.

dysmorphisms

Physical features that are different from what is commonly seen and may sometimes point to a genetic syndrome.

molecular diagnosis

A diagnosis made by finding a specific genetic change that explains the condition.