The 22q11 deletion syndrome is one of the most common multiple anomaly syndromes in humans and has historically been referred to as Velocardiofacial syndrome, DiGeorge sequence, conotruncal anomalies face syndrome, CATCH 22, and Sedlackova syndrome—different names describing the same disorder. This syndrome has an expansive phenotype with more than 180 clinical features that can involve every organ and system. The syndrome is caused by a microdeletion of chromosome 22 at the q11.2 band. The syndrome has a prevalence of approximately 1 in 2,000 in the United States, although incidence is higher. The majority of patients have a constellation of abnormalities resulting from an embryogenic disruption in the formation of the third and fourth aortic arches. The common clinical features are hypocalcemia, immunodeficiency, dysmorphic facial features, palatal and velopharyngeal dysfunction, renal anomalies, and congenital heart disease (CHD). The DiGeorge variant is characterized by thymic and parathyroid aplasia and/or hypoplasia, cardiovascular defects, and dysmorphic facies. Depending on the extent of the thymic hypoplasia, clinical manifestations can range from frequent upper respiratory tract infections to severe immunodeficiency that can only be corrected with cultured thymic tissue transplant, bone marrow transplant, or peripheral blood transplant.

Congenital heart defects are found in 80% of patients with this syndrome. Most of these patients have conotruncal defects with additional anomalies of the aortic arch, pulmonary arteries, infundibular septum, and semilunar valves. The most common abnormalities include tetralogy of Fallot, pulmonary atresia with ventricular septal defect (VSD), truncus arteriosus, IAA, isolated anomalies of the aortic arch, and VSD. These defects arise during the crucial developmental stages of the truncoconal parts of the heart from the pharyngeal pouch derivatives. Cardiac MRIs are invaluable in defining the cardiac and associated anatomy in detail.

Because of errors of embryogenesis of the third and fourth pharyngeal arches, parathyroid hypoplasia and/or aplasia is common and results in hypocalcemia. This can be transient in neonates or may be permanent requiring calcium and vitamin D supplementation. Because hypocalcemia can be difficult to detect in the neonate, a high index of suspicion is necessary if a neonate exhibits irritability, jitteriness, twitching, seizure activity, failure to thrive,
tachycardia, and hypotension. Stridor (which needs to be differentiated from laryngeal web which is also prevalent in 22q11 deletion syndrome) and carpopedal spasm may also occur. It is important to remember that in patients with this syndrome, hypocalcemia may be precipitated by the stress of surgery and by increased needs during puberty or pregnancy. Chronic hypocalcemia may result in poor dentition that is prone to caries.

The prevalence of thyroid disease is significantly higher in the pediatric population with 22q11 deletion syndrome than in the general pediatric population. Shugar et al. suggest that screening for thyroid disease should be added into the routine medical management of these children.

Patients with this syndrome demonstrate marked variability in their immune system ranging from complete thymic aplasia to reduced T-cell counts and function. The majority of patients (˜75% to 80%) have a decrease in the total number of T cells, whereas 20% have no laboratory evidence of reduced T-cells numbers, and ˜1% of patients have thymic aplasia requiring transplant. Reduced levels of immunoglobulin A (IgA) and immunoglobulin M (IgM) also occur more frequently compared to the general population. In most individuals, the T-cell deficiency undergoes spontaneous improvement, usually by 2 years of age. Nonetheless, almost all patients have a tendency toward infection, particularly of the respiratory tract. As long as there is a working thymus, patients with 22q11 deletion syndrome can be immunized and generate a good antibody response because humoral immunity is usually intact. Autoimmune conditions are found in up to a third of patients, the most common being juvenile chronic arthritis, autoimmune thrombocytopenia, hemolytic anemia, Raynaud phenomena, and autoimmune thyroid disease.

Neck masses can originate from a congenital anatomic anomaly, neoplasm, or infection. In the first category are branchial and thyroglossal duct cysts and failed thymic descents. In the embryo, branchial cysts arise from the thymic stalk or the pharyngeal pouch and may be present at birth or develop later. They lie beneath the sternocleidomastoid muscle and may bulge out from its anterior border. The branchial cysts can become infected and enlarge to the extent that they compress the airway or upper esophagus. Thyroglossal duct cysts are spherical, midline masses that may extend back to the base of the tongue and may represent all of the thyroid tissue that the neonate has. In the embryo, the thymus gland arises high in the neck and descends into the anterior mediastinum. If there is any interruption of this caudad movement, the thymus can appear as a soft, compressible mass anywhere along the anterior border of the sternocleidomastoid muscle.

Infectious masses can be due to tuberculosis, Kawasaki disease, Epstein-Barr viral infection, cellulitic facial infections (Ludwig angina), and subacute regional lymphadenitis (catscratch disease).

Neoplastic masses in the cervical region can be teratomas, hemangiomas, neurofibromas, lymphomas, goiters, or cystic hygromas. Teratomas are firm, midline masses arising adjacent to the thyroid isthmus. Hemangiomas may be extensive, consequently compressing vital structures. Neurofibromas may arise individually or as a consequence of neurofibromatosis (von Recklinghausen disease) and can be very large. Goiters are enlarged thyroid glands that may present a hypothyroid, hyperthyroid, or euthyroid state.

Cystic hygroma is a developmental malformation of the lymphatic system found most often in the posterior triangle of the neck and axilla of children. They are divided into suprahyoid and subhyoid masses. They are compressible masses that are most often found in infants younger than 1 year and can intermittently enlarge. Suprahyoid masses can be extremely difficult to manage because of the associated obstructive symptoms, feeding difficulties, and potential for infection, which further can compromise airway patency. Complete surgical removal of these masses is often impossible. Repeat debulking is sometimes the only treatment. Facial paresis is always a potential risk of the resection. The mortality of a prenatally diagnosed cystic hygroma with obstructing features exceeds 20% following delivery. Therefore, intubation of the neonate during delivery while maintaining uninterrupted maternal-fetal circulation until the airway is secured (ex utero intrapartum treatment [EXIT] procedure) has been performed to prevent the fatal consequences of immediate postnatal airway obstruction. Bleomycin or derivatives of Streptococcus pyogenes have been used as sclerosing agents with favorable results.

An IAA anomaly is extremely rare and represents approximately 1% of CHD. In IAA, there is complete aorta atresia somewhere along its arch, which is usually associated with a VSD and other complex cardiovascular anomalies. This defect is categorized into three types depending on where the atresia occurs. Left untreated, it is uniformly lethal within 1 week of life as a result of closure of the ductus arteriosus. In type A (43%), the aorta is interrupted between the left subclavian artery and the aortic isthmus. In type B (the most common, 57%), the interruption lies between the left common carotid and the left subclavian arteries. With type C (least common type, <1%), the arch is interrupted between the innominate and the left common carotid arteries. Forty percent to 50% of patients with IAA have the 22q11.2 deletion, which is usually associated with a more proximal location of the arch interruption (type C or type B).

IAA is a neonatal medical emergency. It warrants immediate infusion of prostaglandin E₁ (PGE₁) to maintain ductal patency as well as stabilizing coexisting CHF. Due to the discontinuity between the descending aorta and the arch, blood flow to the descending aorta and its tributaries cannot occur unless the ductus arteriosus stays open. After medical stabilization, surgical correction should occur as soon as possible because the median age of death in untreated IAA with associated cardiac anomalies is 10 days. The cause of death is usually a combination of greatly increased left-to-right shunt with increased pulmonary blood flow, which results in biventricular failure, pulmonary edema, ductal stenosis, the sequelae of renal failure, and metabolic acidosis. Pulse oximetry will reveal normal saturation in the right arm, with a decreased saturation in the lower extremities. If there is inadequate perfusion to the lower body because of ductal closure, death quickly ensues from the combination of increased left-to-right shunt with increased pulmonary blood flow via the VSD, biventricular CHF, pulmonary edema, renal insufficiency, severe metabolic acidosis, and shock. Symptoms of ductal closure include tachypnea, lethargy, and poor feeding. A transthoracic echocardiography is diagnostic.