SNP Shot: Genomic Insights

Miller-Dieker syndrome is a disorder characterized by lissencephaly, an atypical brain development. Normally, the brain's outer layer (cerebral cortex) has multiple layers with folds and grooves. In individuals with lissencephaly, the brain surface is unusually smooth with fewer folds. These brain abnormalities lead to significant intellectual disability, delayed development, seizures, increased muscle stiffness (spasticity), decreased muscle tone (hypotonia), and difficulty with feeding. Seizures commonly begin before six months of age, sometimes even at birth. Generally, a smoother brain surface correlates with more severe symptoms.

Besides lissencephaly, individuals with Miller-Dieker syndrome often exhibit distinct facial features such as a prominent forehead, a sunken midface (midface hypoplasia), a small upturned nose, low-set and abnormally shaped ears, a small jaw, and a thick upper lip. Some affected individuals experience slower growth compared to other children. In rare cases, individuals may have heart or kidney defects, or an omphalocele (an opening in the abdominal wall) causing abdominal organs to protrude through the navel. Breathing difficulties, which can be life-threatening, are also possible. Sadly, most individuals with Miller-Dieker syndrome do not survive past childhood.

Inheritance:

In most instances, Miller-Dieker syndrome is not inherited. The genetic deletion usually occurs randomly during the formation of egg or sperm cells, or early in fetal development. Therefore, affected individuals typically have no family history of the condition. When Miller-Dieker syndrome *is* inherited, it follows an autosomal dominant pattern because a deletion in one copy of chromosome 17 in each cell is enough to cause the disorder. About 12 percent of individuals with Miller-Dieker syndrome inherit a chromosome abnormality from a parent who is unaffected. These parents carry a balanced translocation, a chromosomal rearrangement where no genetic material is lost or gained. Balanced translocations typically cause no health issues in the parent; however, they can become unbalanced when passed on. Children who inherit an unbalanced translocation can have extra or missing genetic material. Those with Miller-Dieker syndrome who inherit an unbalanced translocation are missing genetic material from the short arm of chromosome 17, leading to the characteristic health problems of the syndrome.