SNP Shot: Genomic Insights

Developmental and epileptic encephalopathy type 1 (DEE1) is a seizure disorder marked by infantile spasms, a specific type of seizure. These spasms generally start before a child's first birthday. While variations exist, the most common spasm involves bending at the waist and neck with arms and legs extended, sometimes referred to as a jackknife spasm. These spasms are brief, lasting only seconds, but occur in clusters spanning several minutes, particularly after waking. Although typically absent during sleep, infantile spasms usually cease by age 5, but many affected children subsequently develop other seizure types that persist throughout life.

Infants with DEE1 often exhibit distinct electroencephalogram (EEG) results. An EEG measures the brain's electrical activity. Typically, these individuals display an irregular EEG pattern called hypsarrhythmia, which aids in distinguishing infantile spasms from other seizure types.

Babies with DEE1 experience developmental delays early in life, ceasing normal progress and regressing in acquired skills like sitting, rolling, and babbling. Intellectual disability is also common and often lasts a lifetime.

Inheritance:

DEE1 follows an X-linked recessive inheritance pattern. The ARX gene, responsible for DEE1, resides on the X chromosome, one of the two sex chromosomes. Males, possessing only one X chromosome, require only one altered copy of the ARX gene in each cell to manifest the condition. Females, with two X chromosomes, generally need mutations in both copies for the disorder to develop. However, a single altered copy can sometimes be sufficient in females due to X-inactivation, a process that silences one of the X chromosomes. Early in female embryonic development, one X chromosome is permanently inactivated in somatic cells (non-reproductive cells) to ensure a balanced expression similar to males. Typically, X-inactivation occurs randomly, leading to approximately equal activity of each X chromosome across cells. Skewed X-inactivation occurs when one X chromosome is active in a disproportionate number of cells. Certain ARX gene mutations may be linked to skewed X-inactivation, leading to the inactivation of the X chromosome carrying the normal ARX gene in a majority of the body's cells. This skewed inactivation results in increased expression of the mutated ARX gene, causing DEE1. A defining characteristic of X-linked inheritance is that fathers cannot transmit X-linked traits to their sons.