DiGeorge/Velocardiofacial Syndrome

Overview
  • DiGeorge and Velocardiofacial Syndrome are both due to deletions of Band 11 on the long-arm of Chromosome 22 (22q11). They were once thought to be distinct diseases but because they share a common genetic etiology are now considered a single pathological entity. Differences in clinical manifestation of this disease appear to be due to different extents of Band 11 deletion. These fascinating entities manifest as syndromes of endocrine, immune, cardiac, and facial skeletal pathology.
Clinical Consequences
  • Overview
    • The basic defect in these diseases is a derangement in the development of the pharyngeal pouches, especially the third and fourth. Consequently, all of the clinical consequences are due to defects in structures derived from these pharyngeal pouches. For any given patient, the spectrum of the disorder may tilt toward a DiGeorge picture or a Velocardiofacial picture, although most patients present with a mixture of symptomology. Below we give the extreme endpoints of the DiGeorge-Velocardiofacial spectrum.
  • DiGeorge Syndrome
    • Developmental defects are more focused on the third and fourth pharyngeal pouches which specifically give rise to the thymus and parathyroid gland. Defective parathyroid gland development leads to hypoparathyroidism and hypocalcemia. Thymic hypoplasia renders T-cell Development highly defective, results in severely reduced numbers of T-cells, and thus impaired Cell-mediated Immunity. This yields an infection susceptibility especially to viral and fungal infections. In most cases, B-cells and Humoral Immunity are relatively intact although in severe T-cell deficiencies even Humoral Immunity is impaired given the role of CD4+ T-cells in Humoral Immunity.
  • Velocardiofacial Syndrome
Mnemonic: CATCH-22
  • C: Congenital Heart Disease
  • A: Abnormal Facies
  • T: Thymic Hypoplasia
  • C: Cleft Palate
  • H: Hypocalcemia due to Hypoparathyroidism
  • 22: Chromosome 22 deletion