DiGeorge Syndrome: Pathogenesis and Clinical Findings

DiGeorge Syndrome: Pathogenesis and clinical findings
Authors: Danielle Lynch Reviewers: Meghan Jackson, Sean Doherty Yan Yu*, Luis Murguia Favela* * MD at time of publication
Note: *TBX1 is most strongly associated with the signs of DiGeorge syndrome, however 30-40 genes reside in the deleted region (e.g. DGCR8 & COMT), though their role is less well understood.
• PA-VSD – pulmonary atresia
with ventricular septal defect
• TBX1 – T-box Protein 1
• VSD – ventricular septal defect
Heterozygous deletion at chromosomal region 22q11.2
The region’s main gene product, TBX1*, exhibits haploinsufficiency: even a heterozygote for this gene product, producing half the normal quantities of TBX1, is insufficient to produce a normal phenotype
Abnormal pharyngeal arch development
Hypoplastic / aplastic thymus ↓ T cells
Craniofacial malformations (e.g. tracheomalacia, horizontal Eustachian tubes, cleft palate)
Impaired ear and sinus drainage
Abnormal conotruncus development
Heart defects
(e.g. interrupted aortic arch, tetralogy of Fallot, PA-VSD/VSD, truncus arteriosus)
Hypoplastic parathyroid glands
Hypocalcemia Seizures
(usually neonatal onset)
Memory Aid:
Cyanotic congenital heart disease
Abnormal facies
Thymic hypoplasia Cognitive impairment Hypoparathyroidism, hypocalcemia
22q11.2 deletion
Abnormal T cell regulation
and development
Compromised cytotoxic T cells
Susceptibility to intracellular pathogens
Compromised helper T cells
↓ communication with memory B cells
(progressive hypogammaglobulinemia)
Susceptibility to extracellular pathogens
Autoimmunity and Atopy
Note: There is phenotypic variability in DiGeorge Syndrome. Other features include: thin upper lip, upslanted palpebral fissures, prominent nose, low-set ears, small mouth, hearing impairment, long tapered fingers, scoliosis, vertebral malformations, learning disabilities, and failure to thrive.
Viral Infections
Bacterial Infections
Sign/Symptom/Lab Finding
Published April 21, 2019 on www.thecalgaryguide.com