DiGeorge Syndrome

What is DiGeorge Syndrome?

DiGeorge syndrome is a genetic condition where a small part of chromosome 22 is missing. A patient with DiGeorge syndrome is missing a segment in one copy of chromosome 22 at a location called q11.2 (22q11.2 deletion syndrome). The deletion can involve many genes that are close together. The signs and symptoms vary depending on the number of genes lost. Depending on the features, some of the subtypes are named CATCH22, velocardiofacial syndrome, Shprintzen syndrome, conotruncal anomaly face syndrome, Sedlackova syndrome, Cayler cardiofacial syndrome or Opitz GBBB syndrome.

About 1 in every 3000 to 4000 children are born with this problem. Although most children acquire this as a new mutation, it can be inherited in an autosomal dominant pattern, meaning any patient who has this deletion has a 50% chance of having a child with the same condition.

What are the common signs and symptoms of DiGeorge Syndrome?

This deletion results in the abnormal development of several body systems and signs and symptoms associated with 22q11.2 deletion syndrome may vary. Some signs and symptoms may be apparent at birth, but others may not appear until later in infancy or early childhood.

What are the common endocrinologic problems?

• Hypoparathyroidism: The parathyroid glands are located adjacent to the thyroid and are 4 small glands that are needed for normal calcium and phosphorus balance. These may not develop properly or may be small. Some children may have problems with regulating blood levels of calcium and phosphorus. This can happen in the newborn period or later. The low levels of calcium in blood may require an endocrinologist to provide calcium supplementation along with a special form of vitamin D. Some patients may only have low calcium levels during stressful periods. Some patients may have deficiencies in the enamel of their teeth. Hypoparathyroidism

• Short stature, failure to thrive, delayed growth, and growth hormone deficiency (especially if there are defects in the midline such as cleft lip and cleft palate). Growth hormone deficiency

• Thyroid disorders: Increased risk of congenital hypothyroidism and autoimmune disorders such as hyperactive or hypoactive thyroid glands (Graves’ disease or hypothyroidism). Congenital Hypothyroidism and Graves’ disease

What are some of the other signs and symptoms observed in children with 22q11.2 deletion syndrome?

• Heart murmur and heart defects
• Immunological issues: the thymus gland may be small or missing, resulting in poor immune function and frequent, severe infections due to abnormal T-cells
• Facial features, such as a small head, underdeveloped chin, low set ears with squared upper ear, wide-set eyes, a narrow groove in the upper lip, a gap in the roof of the mouth (cleft palate) or other problems with the palate
• Skeletal abnormalities, such as scoliosis with or without vertebral anomalies, clubbed feet, extra digits, and craniosynostosis (where the sutures of the skull close too early)
• Delayed development, learning delays or disabilities, behavioral and emotional problems- attention deficit hyperactivity disorder (ADHD) and developmental conditions such as autism spectrum disorders that affect communication and social interaction.

• Other problems: hearing impairment, poor vision, breathing problems, poor kidney function, a decrease in blood platelets (thrombocytopenia), significant feeding difficulties, gastrointestinal problems, and psychiatric disorders.

How is DiGeorge Syndrome treated?

There is no genetic treatment. In severe immune deficiencies, a bone marrow transplantation may be required. However, appropriate medical management can help with associated problems, and early intervention services may be beneficial if initiated in the newborn/early infancy period. This requires the involvement and coordination of different specialists to address the medical and psychosocial aspects.

The low levels of calcium in the blood may require an endocrinologist to provide calcium supplementation along with a special form of vitamin D.  Growth hormone deficiency may require treatment with growth hormone. Similarly, thyroid abnormalities will require evaluation by an endocrinologist and may require treatment with medication.

Children with this condition may need the help of specialists of multiple specialties including Genetics, Endocrinology, Cardiology, Immunology, Ear, Nose and Throat, Gastroenterology, Child Development and Psychology, Audiology, and Orthopedics.

Pediatric Endocrine Society

Section on Endocrinology Patient Education Committee