Diagnostic Tests and Imaging

Confirming a diagnosis of Developmental and Epileptic Encephalopathy 85 (DEE85) is a process of looking both at the “software” of the brain (the genetic code) and its “hardware” (the physical structure). Because this condition is so rare and its physical features can be subtle, specialized tools are required to provide a clear answer.

Genetic Testing: Whole Exome Sequencing (WES) and Panels

While some genetic conditions can be identified by looking at a child’s facial features or growth patterns, DEE85 does not have a single, recognizable “look” (phenotype) that applies to every child ^[1][2]. For this reason, Whole Exome Sequencing (WES) or a targeted epilepsy panel is often required for diagnosis ^[1].

• How it Works: WES does not just look at one gene; it scans all the “exons”—the parts of the DNA that provide instructions for making proteins ^[3].
• Why it’s Preferred: In many cases of epilepsy and developmental delay, WES has a higher “diagnostic yield” (success rate in finding the cause) than smaller, targeted gene panels ^[3][4]. It is particularly effective at finding the various types of SMC1A variants—such as frameshift or nonsense mutations—that cause DEE85 ^[1][5]. Exome testing can sometimes miss copy-number or mosaic variants; if testing is negative or results in a “Variant of Uncertain Significance” (VUS), ask your geneticist about re-testing or periodic data reanalysis.

Brain Imaging: What the MRI Reveals

Once a genetic diagnosis is confirmed, doctors use Magnetic Resonance Imaging (MRI) to look at the physical layout of the brain. While the genetic change is present in every cell, it does not always cause a change you can see on a scan. In fact, in a small study of females with DEE85-causing variants, 62% had a completely normal brain MRI ^[6].

However, approximately 20% of children with DEE85 are found to have Central Nervous System (CNS) malformations ^[1].

Understanding Structural Brain Findings

The “midline” refers to the structures that sit directly in the center of the brain, acting as bridges or anchors between the left and right sides. In DEE85, several specific areas are carefully evaluated by neuroradiologists:

• Corpus Callosum: This is the main “bridge” of nerve fibers connecting the two halves of the brain. Some children with DEE85 have a thin corpus callosum, which can affect how the two sides of the brain communicate ^[6].
• Cerebellum: Located at the back of the brain (posterior fossa), this area controls balance and motor coordination. Reports have noted cerebellar atrophy (thinning or shrinking of this tissue) in some patients ^[6][7].
• Ventricles: These are the paired fluid-filled spaces inside the brain. An MRI may show ventricular enlargement, which has many possible causes and does not automatically mean surrounding brain tissue is damaged ^[6].

Why Imaging Matters

It is important to remember that having a structural brain defect does not change the diagnosis—the diagnosis is defined by the SMC1A variant and the presence of seizures ^[1]. However, knowing if a defect is present helps your care team:

1. Refine the Clinical Picture: It helps explain specific physical challenges, such as difficulties with balance if the cerebellum is involved ^[7].
2. Monitor Progress: A structural finding does not automatically require serial MRIs; follow-up scans should only be performed when your neurologist identifies a specific clinical indication ^[7].
3. Differentiate from Other Conditions: While DEE85 shares a gene with Cornelia de Lange Syndrome (CdLS), the structural brain findings in DEE85 are often more central to the child’s neurological challenges ^[1].

Your child’s MRI report may contain complex terms, but its primary purpose is to help your neurologist see the “map” of your child’s brain as they navigate the path of treatment.