SNP Shot: Genomic Insights

22q11.2 deletion syndrome, also known by other names, arises from a missing segment of chromosome 22. This deletion occurs at the q11.2 location, situated near the chromosome's center.

The syndrome presents a wide range of signs and symptoms impacting various parts of the body. These features differ significantly, even among family members with the syndrome. Common characteristics include heart defects present at birth, frequent infections due to immune system issues, and distinct facial features. Some individuals have an incompletely closed palate, known as submucosal cleft palate, despite intact tissue coverage. This often manifests as a high-arched palate or a split uvula. Submucosal cleft palate can cause nasal-sounding speech due to air escaping through the nose. Additional problems may include breathing difficulties, kidney abnormalities, low blood calcium (potentially leading to seizures), reduced blood platelets (thrombocytopenia), feeding challenges, gastrointestinal issues, and hearing loss. Skeletal variations are possible, such as mild short stature and, less commonly, spinal bone abnormalities.

Many children with 22q11.2 deletion syndrome experience developmental delays, affecting growth and speech. Some have mild intellectual disability or learning challenges. Older individuals may struggle with reading, math, and problem-solving. Behavioral adaptation can also be difficult, requiring support. These children have a higher likelihood of developing attention-deficit/hyperactivity disorder (ADHD) and conditions like autism spectrum disorder, which affects communication and social interaction.

The diverse range of symptoms led to the initial identification of separate conditions based on specific groupings of features. These conditions were named DiGeorge syndrome, velocardiofacial syndrome (Shprintzen syndrome), and conotruncal anomaly face syndrome. Additionally, some children were diagnosed with forms of Opitz G/BBB syndrome and Cayler cardiofacial syndrome. Once the genetic basis was understood, these were recognized as variations of a single syndrome. The term "22q11.2 deletion syndrome" is now preferred to accurately reflect the underlying genetic cause and avoid confusion.

Inheritance:

22q11.2 deletion syndrome follows an autosomal dominant inheritance pattern. This means that a deletion in just one copy of chromosome 22 is enough to cause the condition. However, most cases occur spontaneously, resulting from a random event during the formation of egg or sperm cells, or early in fetal development. These individuals typically have no family history of the disorder, but can pass it on to their children. Approximately 10% of cases are inherited from a parent with the deletion. In these inherited cases, other family members may also be affected.