Are 22q11.2 distal deletions associated with math difficulties?

Area of Science:

• Neurogenetics
• Developmental Pediatrics
• Human Genetics

Background:

• Math difficulties (MD) affect approximately 6% of school-aged children.
• A neurogenetic basis for MD is suspected, with links to genetic syndromes like 22q11.2 deletion syndrome (22q11.2DS).
• The specific contribution of 22q11.2DS to the MD phenotype remains under-investigated.

Purpose of the Study:

• To determine the frequency of 22q11.2DS in school children with MD.
• To characterize a potential new syndrome associated with a specific 22q11.2 deletion.
• To explore the role of 22q11.2DS as a genetic cause of MD.

Main Methods:

• Population-based screening of 1,564 school children for language and math abilities.
• In-depth assessments (intelligence, neuropsychological, math cognition) of 152 selected children (82 with MD, 70 controls).
• MLPA screening for 22q11.2 microdeletion in selected children.

Main Results:

• One child in the MD group presented with a 22q11.2 deletion (LCR22-4 to LCR22-5 interval).
• This child exhibited subtle anomalies, normal intelligence, MD due to number sense deficit, and social interaction difficulties.
• Review of 19 reported cases allowed characterization of 22q11.2 DS (LCR22-4 to LCR22-5) with distinct features, including learning disability and MD in one instance.

Conclusions:

• 22q11.2 deletion syndrome (LCR22-4 to LCR22-5) is identified as a potential genetic cause of math difficulties.
• This specific deletion may represent a distinct syndrome contributing to learning disabilities.
• Further research is warranted to elucidate the genetic underpinnings of MD.