DiGeorge Syndrome in Adults: Cardiac, Endocrine, and Neuropsychiatric Aspects

DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a genetic condition affecting multiple body systems. While often diagnosed in childhood, many adults live with its effects, sometimes without realizing they have the disorder. The condition can significantly impact the heart, endocrine system, and mental health.

Recognizing these complications in adulthood is essential for improving long-term outcomes. Understanding the syndrome’s effects can help individuals seek appropriate medical care and support.

Cardiac Involvement

Congenital heart defects are among the most serious manifestations of DiGeorge syndrome in adults. Common anomalies include tetralogy of Fallot, interrupted aortic arch, and truncus arteriosus, which can lead to heart failure, arrhythmias, and aortic dilation. While many individuals undergo corrective surgery in childhood, residual defects and progressive cardiovascular changes necessitate ongoing surveillance.

Adults with repaired tetralogy of Fallot often develop right ventricular dysfunction and pulmonary valve insufficiency, sometimes requiring reintervention. A 2021 review in Circulation found that up to 50% of adults with repaired congenital heart disease experience arrhythmias, including atrial fibrillation and ventricular tachycardia, increasing the risk of stroke and sudden cardiac events. Regular electrocardiographic monitoring and, in some cases, antiarrhythmic therapy or implantable cardioverter-defibrillators (ICDs) are often necessary.

Vascular abnormalities such as aortic root dilation and aneurysm formation also present concerns. A study in The Journal of the American College of Cardiology found that adults with 22q11.2 deletion syndrome have a higher prevalence of aortic enlargement, even without significant congenital heart disease. Routine imaging via echocardiography or cardiac MRI is recommended to monitor for progressive dilation, with blood pressure management using beta-blockers or angiotensin receptor blockers to reduce stress on the aortic wall.

Beyond structural and vascular abnormalities, functional impairments like reduced myocardial contractility and diastolic dysfunction have been reported. A 2022 meta-analysis in The Lancet indicated that adults with congenital heart disease related to 22q11.2 deletion syndrome have a higher prevalence of heart failure. Management typically includes guideline-directed medical therapy with ACE inhibitors, diuretics, and, in severe cases, heart transplantation.

Endocrine Factors

Hormonal dysregulation is common in DiGeorge syndrome, often due to congenital defects in the parathyroid glands. Hypoparathyroidism leads to impaired calcium homeostasis, resulting in chronic hypocalcemia. Symptoms such as muscle cramps, tetany, paresthesia, and seizures can occur if calcium levels are not maintained. A study in The Journal of Clinical Endocrinology & Metabolism found that up to 60% of adults with 22q11.2 deletion syndrome exhibit some degree of parathyroid dysfunction, requiring lifelong monitoring and supplementation with calcium and active vitamin D analogs.

Thyroid abnormalities, particularly hypothyroidism, are also common. While some cases are congenital, others develop later in life, possibly due to autoimmune thyroiditis. A 2022 study in Thyroid found that approximately 30% of adults with DiGeorge syndrome had subclinical or overt hypothyroidism, contributing to fatigue, weight gain, and cognitive impairment. Regular screening with serum TSH and free T4 measurements is recommended, with levothyroxine replacement initiated as needed.

Glucose metabolism disturbances, including type 2 diabetes and insulin resistance, are more prevalent in adults with DiGeorge syndrome. Contributing factors may include altered pancreatic development, obesity, and antipsychotic medications. A population-based study in Diabetes Care found a 2.5-fold increased risk of diabetes in adults with 22q11.2 deletion syndrome. Routine glucose monitoring and lifestyle modifications are key, with pharmacologic interventions like metformin or GLP-1 receptor agonists considered for persistent hyperglycemia.

Growth hormone deficiency, though more commonly identified in childhood, can persist or emerge later, contributing to reduced bone density, increased adiposity, and diminished muscle mass. A 2021 review in The Journal of Clinical Endocrinology & Metabolism found that untreated growth hormone deficiency in adults with DiGeorge syndrome was linked to lower bone mineral density and increased fracture risk. DEXA scans are recommended to assess bone health, with bisphosphonates or recombinant growth hormone therapy considered in select cases.

Neuropsychiatric Components

Cognitive and psychiatric challenges are common in adults with DiGeorge syndrome, often affecting intellectual ability, executive function, and mood. Many individuals struggle with working memory, attention, and problem-solving, impacting daily functioning and employment. Neuroimaging studies have identified structural brain differences, including reduced volume in the prefrontal cortex and hippocampus, which correlate with difficulties in adaptive functioning.

Schizophrenia is one of the most well-documented psychiatric associations, affecting up to 30% of individuals with 22q11.2 deletion syndrome. Functional MRI studies suggest altered connectivity in the default mode network, contributing to psychotic symptoms. Antipsychotic medications are commonly prescribed, though individuals with this genetic condition often exhibit heightened sensitivity to side effects. Second-generation antipsychotics such as aripiprazole or lurasidone are preferred due to their lower dopamine blockade.

Anxiety and depression are also common, often exacerbated by social difficulties and the stress of managing multiple medical conditions. A longitudinal study in The American Journal of Psychiatry found that over 50% of adults with DiGeorge syndrome experience generalized anxiety disorder or major depressive disorder. Cognitive-behavioral therapy (CBT), particularly when adapted for cognitive impairments, has shown promise. SSRIs may be beneficial, though careful monitoring is required due to potential side effects.

Screening And Diagnosis In Adults

Many adults with DiGeorge syndrome remain undiagnosed, as their symptoms may be mild or attributed to other conditions. Definitive diagnosis requires molecular testing, yet this is not routinely performed in adults unless clinical suspicion arises. A delayed diagnosis can lead to years of unexplained health issues, particularly for individuals with isolated features such as psychiatric symptoms, endocrine dysfunction, or congenital heart disease.

A targeted screening approach includes a thorough clinical evaluation and personal and family history. Adults with unexplained congenital heart anomalies, recurrent hypocalcemia, or neurodevelopmental conditions should be considered for genetic testing. Fluorescence in situ hybridization (FISH) was historically the standard diagnostic method, but chromosomal microarray analysis and next-generation sequencing now provide more sensitive detection. Genetic counseling is recommended, as individuals with DiGeorge syndrome have a 50% chance of passing the deletion to their offspring.

Community And Social Resources

Navigating adulthood with DiGeorge syndrome presents challenges in healthcare, employment, and social relationships. Many adults require ongoing medical supervision, yet access to specialized care can be inconsistent. Transitioning from pediatric to adult healthcare services is often difficult, as fewer providers are familiar with the syndrome’s complexities. Advocacy organizations such as the 22q Family Foundation and the International 22q11.2 Foundation help connect individuals with knowledgeable healthcare professionals, provide educational resources, and foster peer support networks.

Social integration and occupational opportunities significantly influence quality of life. Many adults with DiGeorge syndrome experience difficulties with executive function and social cognition, affecting workplace performance and independent living. Vocational training programs tailored to individuals with cognitive challenges can enhance job readiness, while supported employment initiatives provide accommodations for success in the workforce. Social support groups offer structured environments for developing interpersonal skills and building confidence. In some cases, assisted living arrangements or community-based services may be beneficial for individuals requiring additional support. Accessing these resources early in adulthood can improve long-term stability and overall well-being.