What is the chance of a 22q deletion occurring?

Incidence of 22q11.2 Deletion Syndrome

22q11.2 deletion syndrome occurs in approximately 1 in 2,000 to 1 in 4,000 live births, making it the most common microdeletion syndrome in humans. 1, 2, 3

Population Prevalence

• The American College of Medical Genetics and Genomics reports the incidence as 1 in 2,000 to 1 in 3,000 live births based on genetic studies 1
• Alternative estimates place the frequency at 1 in 4,000 live births 2
• This represents the most common microdeletion syndrome affecting humans 1

Inheritance Patterns and Recurrence Risk

The majority (85-95%) of cases occur as de novo deletions, meaning they arise spontaneously rather than being inherited from a parent 4, 1

• Only 5-10% of cases are inherited from an affected parent 4, 1
• Among inherited cases, up to 25% of deletions are familial 1
• One large cohort study found 17.2% parental transmission rate, with preferential maternal transmission (10 of 15 cases) 5
• In the Children's Hospital of Philadelphia cohort of 1,421 patients, only 7% of typical deletions were inherited from a parent 3

Recurrence Risk for Affected Individuals

Affected individuals have a 50% chance of transmitting the deletion to each offspring, regardless of whether they are male or female 4, 1, 6

• This 50% recurrence risk applies to all affected individuals due to the autosomal dominant inheritance pattern 4
• Offspring of affected individuals also have an increased risk of congenital heart defects beyond the baseline 50% deletion transmission risk 6
• When neither parent has the deletion (de novo case), there is a small elevated recurrence risk in future pregnancies due to rare germline mosaicism 4

Clinical Implications for Detection

Many adults with 22q11.2 deletion remain undiagnosed, particularly those without typical congenital anomalies or who were born before confirmatory testing became available 4

• The variable phenotype presents significant diagnostic challenges 4
• Many adults are diagnosed only after the birth of an affected child 4
• Some sudden and/or premature deaths in the general population may represent undiagnosed 22q11.2 deletion syndrome 7
• Parental testing should be performed regardless of parental phenotype, as extremely mild clinical features can occur in affected parents 5