Pediatric Endocrinology and Immunology Team at UPMC Children's Collaborate in Dedicated DiGeorge Syndrome Clinic

The Division of Pediatric Endocrinology and Division of Pediatric Allergy and Immunology at UPMC Children's Hospital of Pittsburgh created a dedicated clinic for children with DiGeorge syndrome, also known as 22q11.2 deletion syndrome. The dedicated, multidisciplinary clinic first started seeing patients in December 2024. It brings together pediatric endocrinology, immunology, and nutrition expertise in a single coordinated visit for patients with this complex, multi-system genetic condition.

The Nature of DiGeorge Syndrome

DiGeorge syndrome is the most common autosomal dominant chromosomal deletion condition, though cases of spontaneous 22q11.2 deletion can occur. DiGeorge syndrome is estimated to occur in about one in 4,000 individuals. Advances in genetic testing, particularly in children evaluated for congenital heart disease, has led to more frequent diagnosis in recent years. DiGeorge syndrome typically affects multiple organ systems and can present across a wide spectrum of severity, from mild manifestations identified later in childhood to more severe presentations diagnosed soon after birth. DiGeorge syndrome can, among other complications, affect the thymus and parathyroid gland, lead to congenital heart lesions, cleft palate and other facial manifestations, and difficulties in learning and cognition.

Endocrinology has been at the center of understanding and management of DiGeorge syndrome since the condition was first described in the 1960s by Angelo DiGeorge, MD, a pediatric endocrinologist from Temple University in Philadelphia for whom the condition is named. One of the endocrine complications often seen in patients is hypoparathyroidism. Low parathyroid hormone (PTH) and the hypocalcemia it can produce are the most clinically significant endocrine concerns that patients with DiGeorge syndrome may be exposed to. Hypocalcemia in DiGeorge syndrome can be severe enough to cause cardiac arrhythmias or seizures, and ongoing monitoring is a necessary part of long-term patient care and optimal health outcomes. With thymus involvement often present, patients with DiGeorge syndrome can have varying levels of immune system dysregulation.

Coordinating Care for a Complex Patient Population

The DiGeorge syndrome clinic at UPMC Children’s was created through a collaboration between pediatric endocrinology advanced practice provider, Elizabeth Ranella, CRNP, and Christin Deal, MD, assistant professor of pediatrics, Division of Pediatric Allergy and Immunology.

The dedicated clinic currently runs on a quarterly basis. Along with Ms. Ranella and Dr. Deal, Jillian Willis, RD, a registered dietitian in the Division of Pediatric Endocrinology, also collaborates on patient care in the clinic.

"Bringing together pediatric endocrinology, allergy and immunology, and dietetics in one visit is the right model of care for patients with DiGeorge syndrome. The endocrine piece and the immune piece are both hallmark features of DiGeorge syndrome, and having nutrition built into our multidisciplinary clinic addresses concerns that span both of those areas and really the whole course of the child's care,” Ms. Ranella says.

Having dietetics directly integrated into the clinic structure reflects the prevalence of nutritional complexities patients with DiGeorge syndrome face throughout their developmental years. Feeding difficulties, failure to thrive, and poor weight gain can be common issues in early childhood, particularly if delays in diagnosis occur. At the same time, emerging data suggest that individuals with a 22q11.2 chromosomal deletion carry an increased risk of obesity and type 2 diabetes in adulthood. Recognizing these potential downstream effects are possible allows for more anticipatory guidance for families and patients. From an endocrine standpoint, the three primary areas of longitudinal monitoring in pediatric patients with DiGeorge syndrome are calcium and PTH levels, physical growth patterns and trajectories, and thyroid function. Thyroid disease is known to occur with increased frequency in patients with DiGeorge syndrome and is assessed as part of routine follow-up in the clinic.

"Not every patient needs to see both of us at every visit. Some kids don't have significant immune issues and Dr. Deal may not need to see them until their next vaccine schedule, while others need immunology more urgently. We're able to triage that and coordinate in real time based on each patient's needs,” Ms. Ranella says.

Because of the lack of dedicated clinics nationwide for patients with DiGeorge syndrome (about 21 such clinics currently exist in the United States and one in Canada) many patients travel from significant distances for care.

The UPMC Children’s DiGeorge syndrome clinic works to coordinate same-day appointments with other services when needs are identified in advance. Attention-deficit/hyperactivity disorder, learning disabilities, and behavioral concerns can occur with greater frequency in children with 22q11.2 deletion.

Patient and Family Education and Future Clinic Growth

A dedicated feature of the clinic is expanded time for patient and family education. Compared to some conditions like Down syndrome which is fairly well known and has a robust network of educational offerings, support groups, for families, and the like, similar resources at the same scale do not currently exist for DiGeorge syndrome patients and families making it a somewhat underserved population in this regard.

"We really want families to understand what low calcium feels like, what symptoms to watch for, what to do when their child is sick, and how to use nutrition supplements appropriately,” Ms. Ranella says. “We've developed education materials specifically for the clinic, and having more time to walk through these concerns – like spending focused time on nutrition – with families is valuable. Some of these kids have been followed for years but haven't had a lot of opportunity for that kind of educational visit."

As the clinic continues to grow and mature, the team's goals include expanding the multidisciplinary model to incorporate additional specialty services on a regular basis, potentially including craniofacial and cleft services and behavioral health specialists. A longer-range goal for the program consists of coordinating visits across consecutive days for families traveling long distances, allowing for additional subspecialty appointments in other services to be completed in a single trip.

Dr. Deal also is working toward establishing a patient registry for individuals seen through the clinic, a step that would support longitudinal outcomes tracking and facilitate research collaboration with other DiGeorge syndrome centers around the country.

"There is a lot of interest in building this program and a lot of opportunity to grow it to reach more patients and families in need of specialize care. UPMC Children's is a great institution, and the more we can offer these families in a coordinated way, the better their outcomes will be over time," Ms. Ranella says.

Patient Referrals and Consultations

For patient referrals or consultations, referring providers can email endoreferral@chp.edu.