22q11.2 deletion syndrome, aka DiGeorge syndrome or velocardiofacial syndrome, the chromosomal disorder caused by a small deletion on the long arm of chromosome 22, is one of the most common microdeletion syndromes, and affects multiple organ systems, resulting in a wide spectrum of clinical features that often present in childhood.
Key Features in Pediatrics
Cardiac Anomalies
Congenital heart defects are among the most common early manifestations. These include conotruncal anomalies such as tetralogy of Fallot, truncus arteriosus, interrupted aortic arch, and ventricular septal defects. These cardiac issues may require surgical intervention in infancy or early childhood and often are a key leading to diagnosis.
Immune Deficiency
The deletion frequently affects thymic development, leading to T-cell immunodeficiency. The severity ranges from mild immune dysregulation to severe immunodeficiency. Affected children may present with frequent infections, especially in the first years of life. Newborn screening for T-cell receptor excision circles (TRECs) can help in early detection of immunodeficiency.
Facial Dysmorphism and Palatal Abnormalities
Subtle facial features such as a long face, small chin, hooded eyelids, and low-set ears are common but may go unnoticed. Palatal abnormalities, including cleft palate or velopharyngeal insufficiency, can lead to nasal speech and feeding difficulties, often requiring surgical or speech therapy intervention.
Developmental and Behavioral Challenges
Children with 22q deletion often exhibit developmental delays, particularly in speech and motor skills. Cognitive impairment ranges from borderline to mild intellectual disability, but many children attend mainstream schools with additional support. Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and anxiety disorders are more prevalent in this population. Early intervention with developmental therapies is essential for optimizing outcomes.
Endocrine Issues
Hypocalcemia, due to parathyroid hypoplasia, is another common feature and may cause seizures in the neonatal period. Lifelong monitoring of calcium levels is necessary. Thyroid dysfunction and growth hormone deficiencies are also reported.
Feeding and Gastrointestinal Concerns
Feeding difficulties, gastroesophageal reflux, and failure to thrive are common in infancy and may necessitate specialized feeding interventions. Constipation and gastrointestinal motility issues can persist into childhood.
Hearing and Vision
Hearing loss due to recurrent otitis media or structural abnormalities is common, necessitating audiologic screening. Vision problems such as strabismus or refractive errors may also occur.
Diagnosis and Management
Diagnosis is confirmed via genetic testing, typically using FISH, chromosomal microarray, or MLPA. Multidisciplinary care is crucial, involving cardiology, immunology, endocrinology, speech therapy, developmental pediatrics, and genetics. Regular monitoring and individualized management plans help address the wide range of potential complications.
Long-Term Outlook
With appropriate medical and developmental support, many children with 22q deletion syndrome lead productive lives. However, the variability in presentation means some children face significant medical and developmental challenges. Ongoing research continues to improve understanding of the syndrome and refine management strategies.