22q11.2 Deletion Syndrome: What Pediatricians and Parents Should Know About Identification and Long-Term Care
22q11.2 deletion syndrome, also known as DiGeorge syndrome or velocardiofacial syndrome, is a genetic disorder that may go unrecognized during early infancy despite its relatively common occurrence. Affecting roughly one in every 4,000 live births, this chromosomal condition presents a broad spectrum of symptoms and challenges that can vary significantly between individuals. The variability in the severity and presentation of symptoms means that many children may not receive a timely diagnosis, potentially delaying critical interventions during key stages of development.
The American Academy of Pediatrics (AAP) recently published a clinical report in the August 2025 edition of Pediatrics titled "Health Supervision for Children with 22q11.2 Deletion Syndrome." This report provides detailed guidance to pediatricians aimed at improving the early identification and comprehensive care of children with this complex condition. The report consolidates years of clinical research and expert consensus, offering evidence-based practices that reflect the evolving understanding of this syndrome and its impact on child health.
One of the most challenging aspects of 22q11.2 deletion syndrome is the diverse range of health and developmental issues it can cause. While some children may have only subtle features or mild learning difficulties, others may experience more pronounced symptoms, including congenital heart defects, immune system dysfunctions, endocrine abnormalities, feeding difficulties, and mental health disorders. The syndrome stems from a small missing piece of chromosome 22, specifically the q11.2 region, which is critical to the development of several body systems. Because the deletion can impact different genes and systems, the clinical presentation is highly individualized, complicating efforts to standardize screening and treatment protocols.
The early recognition of 22q11.2 deletion syndrome is vital for ensuring better outcomes. Pediatricians play a pivotal role in identifying early warning signs, such as feeding issues, recurrent infections, delayed speech, low calcium levels leading to seizures, or the presence of characteristic facial features. These features may include low-set ears, a small jaw, hooded eyelids, and a bulbous nasal tip, though not all children will exhibit all or even most of these signs. The variability of presentation necessitates a high degree of clinical suspicion, particularly when multiple systems are involved, and the cause of the child's health issues remains unclear.
In recent years, newborn screening technologies have significantly improved the detection of severe combined immunodeficiency (SCID), a condition that may bring infants with 22q11.2 deletion syndrome to medical attention in the first few days of life. A positive SCID screen, while not diagnostic of 22q11.2 deletion syndrome, can prompt further evaluation that may ultimately lead to a diagnosis. This highlights the importance of integrating genetic testing into the diagnostic pathway when immunodeficiency or other tell-tale symptoms are present.
The majority of children diagnosed with 22q11.2 deletion syndrome are the first in their families to present with the condition, as the deletion often occurs as a de novo event. However, approximately 10% of cases are inherited from an affected parent, making family history a valuable but limited tool in the diagnostic process. Given the potential for inheritance, genetic counseling is strongly recommended for families once a diagnosis is confirmed. Understanding the genetic basis of the disorder empowers families with information regarding recurrence risk in future pregnancies and the possibility that other relatives may be mildly affected without being previously diagnosed.
Early genetic testing plays a crucial role in identifying affected infants and initiating appropriate multidisciplinary care. The AAP report emphasizes the importance of using the most appropriate genetic screening tools, such as chromosomal microarray analysis or FISH (fluorescence in situ hybridization), to detect the 22q11.2 deletion accurately. While prenatal testing can also identify the syndrome, its utility is dependent on clinical suspicion, parental genetic status, or findings during fetal ultrasounds that raise concerns, such as congenital heart anomalies.
Once a diagnosis is confirmed, comprehensive care coordination becomes essential. Children with 22q11.2 deletion syndrome benefit from a collaborative approach involving multiple specialists, including cardiologists, endocrinologists, immunologists, speech and language therapists, developmental pediatricians, and mental health professionals. Congenital heart disease, present in up to 75% of affected individuals, often requires early surgical intervention and ongoing cardiac surveillance. Immune deficiencies, resulting from thymic hypoplasia or aplasia, increase the risk of recurrent infections and require careful immunological monitoring. In some cases, live vaccines may be contraindicated or delayed based on immune status, requiring individualized vaccine schedules.
Feeding and swallowing difficulties are common, especially in infancy and early childhood. These issues may be linked to cleft palate, velopharyngeal insufficiency, or neuromuscular dysfunction, and they can contribute to poor weight gain and growth delays. In such cases, consultation with feeding specialists and nutritionists is vital, and some children may require tube feeding or surgical intervention to correct anatomical defects.
Developmental and behavioral concerns often emerge as the child grows. Mild to moderate intellectual disabilities may be present, and language development is frequently delayed. Children may also exhibit attention-deficit/hyperactivity disorder (ADHD), autism spectrum behaviors, anxiety, or mood disorders. School-age children and adolescents often require special education services or individualized education programs (IEPs) tailored to their specific cognitive and emotional needs. It is also essential to provide families with psychosocial support and access to community resources, as caregiving demands can be intense and ongoing.
Adolescents and young adults with 22q11.2 deletion syndrome may face new challenges, including the emergence of psychiatric illnesses such as schizophrenia or major depression. The risk of psychosis in individuals with this syndrome is significantly higher than in the general population, making early screening and mental health care integral components of long-term management. Transition planning from pediatric to adult care services is critical to ensure continuity of care during this vulnerable period.
In addition to providing clinical recommendations, the AAP report urges pediatricians to communicate effectively with families, offering not only medical guidance but also emotional support and realistic expectations. Parents often experience considerable stress, grief, and anxiety following a diagnosis, and they benefit from empathetic communication, clear explanations of the condition, and referrals to support groups or genetic counseling services. Family-centered care is not only compassionate—it also improves adherence to treatment plans and strengthens the partnership between healthcare providers and caregivers.
Technological advancements and growing awareness have led to improved outcomes for children with 22q11.2 deletion syndrome. Many individuals with the condition can live long, fulfilling lives when provided with timely interventions and consistent, coordinated care. Nevertheless, disparities in access to specialty care, differences in physician awareness, and regional variations in healthcare resources continue to pose barriers. The AAP’s report aims to bridge these gaps by offering a unified framework for best practices, rooted in the latest scientific evidence and shaped by input from clinical experts across disciplines.
Ultimately, the publication of "Health Supervision for Children with 22q11.2 Deletion Syndrome" represents a milestone in pediatric healthcare. It recognizes the complexity of the syndrome and the need for individualized, longitudinal care that evolves with the child's developmental trajectory. By equipping pediatricians with practical tools and clinical insights, the report empowers them to improve outcomes for affected children and their families. As research continues to uncover the genetic mechanisms and phenotypic variability of the syndrome, future updates to these guidelines will likely reflect an even deeper understanding of the condition.
For now, the message is clear: early diagnosis, proactive management, and family-centered care are the cornerstones of effective support for children living with 22q11.2 deletion syndrome. Pediatricians, as the first point of contact for most families, are uniquely positioned to detect warning signs, initiate appropriate testing, and coordinate the comprehensive care that these children need to thrive.