Chapter 216: DiGeorge Syndrome

Patient Story

A newborn infant is noted to have micrognathia, a bulbous nasal tip, a crumpled ear helix (Figure 216-1), hooded eyes, a high arched palate, and a submucosal cleft palate. She was diagnosed prenatally with Tetralogy of Fallot. Tetany due to hypocalcemia is noted in the first 48 hours of life and requires treatment. A chest x-ray obtained is notable for absence of a thymic shadow (Figure 216-2). Immunologic laboratory data reveal CD3+ T cells are <500/mm³. Chromosomal analysis is sent and reveals a deletion of chromosome 22q11.2. She undergoes surgical repair of her heart lesion at one week of age, and requires close follow-up of her cardiac, immunological, and metabolic problems.

Introduction

DiGeorge Syndrome (DGS), also known as 22.q11 deletion syndrome, or velocardiofacial syndrome (VCFS), describes patients with a distinct clinical phenotype. Patients classically present with a triad of conotruncal cardiac anomalies, hypoplastic thymus, and hypocalcemia. However, there is a wide variation in phenotypic presentations.

Synonyms

• Velocardiofacial syndrome (VCFS).

• Chromosome 22q11.2 deletion syndrome (22qDS).

• Congenital Thymic hypoplasia/aplasia.

• Conotruncal Anomaly Face syndrome.

• Shprintzen syndrome.

• Strong syndrome.

Epidemiology

• DGS is the most common microdeletion syndrome.

• Population studies in the US have found an incidence of approximately 1:3,000 to 1:6,000 births.¹

• This incidence may be increasing due to affected parents having their own children, and the incidence may be underestimated because of under diagnosis of patients with mild phenotypic features, particularly in African Americans.²

• DGS has an equal distribution in males and females, races, and geographic location.³

• The syndrome typically presents in infancy but diagnosis may be delayed in patients with partial DGS and mild phenotypes.

Etiology and Pathophysiology

• The features associated with DGS result from dysmorphogenesis of the 3rd and 4th pharyngeal pouches during embryogenesis, leading to thymus or parathyroid gland hypoplasia or aplasia. Related anomalies involve structures forming around the same time, including the great vessels, esophagus, uvula, heart, facial, and ear anomalies.⁴

• The most common genetic deletion is a hemizygous microdeletion from chromosome 22q11.2.³ The size of the deletion does not appear to correlate with the ...