SNP Shot: Genomic Insights

Phelan-McDermid syndrome, also known as 22q13.3 deletion syndrome, results from the loss of a small piece of genetic material from chromosome 22. This deletion happens near the chromosome's end, at a location called q13.3.

The signs and symptoms of 22q13.3 deletion syndrome are highly variable and can affect numerous parts of the body. Common characteristics include developmental delays, ranging from moderate to severe intellectual disability, low muscle tone (hypotonia), and absent or delayed speech. Some individuals with this syndrome are diagnosed with autism spectrum disorder or display autistic-like traits that impact communication and social interaction, such as limited eye contact, tactile sensitivity, and aggressive behavior. They might also engage in pica, the act of chewing on non-food items like clothing. Less commonly, individuals may experience seizures or a loss of previously acquired skills (developmental regression).

People with 22q13.3 deletion syndrome often have a reduced sensitivity to pain. Furthermore, many experience a decreased ability to sweat, potentially leading to overheating and dehydration. Some individuals may suffer from episodes of recurring vomiting and nausea (cyclic vomiting) and the backflow of stomach acid into the esophagus (gastroesophageal reflux).

Individuals with 22q13.3 deletion syndrome often exhibit distinct facial features, such as a long, narrow head, prominent ears, a pointed chin, drooping eyelids (ptosis), and deep-set eyes. Other physical characteristics can include large and fleshy hands and/or feet, fused second and third toes (syndactyly), and small or abnormal toenails. Accelerated growth can also be observed in some affected individuals.

Inheritance:

In most instances, 22q13.3 deletion syndrome is not inherited. The deletion typically arises as a spontaneous event during the formation of reproductive cells (eggs or sperm) or during early fetal development. Usually, affected individuals have no family history of the disorder, although they are capable of passing the chromosome deletion to their offspring. When 22q13.3 deletion syndrome *is* inherited, it follows an autosomal dominant inheritance pattern. This means a deletion in just one copy of chromosome 22 in each cell is enough to cause the condition. Approximately 15 to 20 percent of individuals with 22q13.3 deletion syndrome inherit a chromosome abnormality from a parent who is not affected. In these cases, the parent carries a balanced translocation, where segments from two different chromosomes have switched places without any net gain or loss of genetic material. Balanced translocations typically do not cause health problems in the carrier. However, these translocations can become unbalanced when passed on to the next generation. Children who inherit an unbalanced translocation may have extra or missing genetic material. Individuals with inherited 22q13.3 deletion syndrome have a missing piece of the long arm of chromosome 22, resulting in the characteristic health problems associated with the syndrome.