Genetics
DiGeorge syndrome is caused by a deletion on chromosome 22. Approximately 90% of patients with DiGeorge syndrome have a deletion at the 22q11.2 region. A small number of cases of DGS have defects on other chromosomes, notably 10p13. DiGeorge syndrome is inherited in an autosomal dominant manner.
Incidence
- Affects approximately 1 in 3,000 to 1 in 4,000 individuals
- Most of the 22q11.2 deletion cases are de novo, however in about 10% of families, the deletion is inherited and other family members are affected or at risk for passing this deletion to their children
- There is an overall 0.025% risk of the 22q11 deletion syndrome in the general population
Symptoms/Characteristics
- Conotruncal heart defects (Tetralogy of Fallot, interrupted aortic arch, ventricular septal defects, vascular rings)
- Palatal abnormalities
- Feeding difficulties
- Immunodeficiency due to absence or malformation of thymus
- Hypocalcemia due to absence of malformation of parathyroid glands
- Craniofacial abnormalities (see below)
- Hearing loss or abnormal ear exams
- Genitourinary anomalies (absent or malformed kidney)
- Mental retardation (typically borderline to mild)
- IQs are generally in the 70 to 90 range
- Psychiatric disorders in adults (e.g., schizophrenia, bipolar disorder)
- Autism
Facial Features
- Small ears with squared upper ear
- Hooded eyelids
- Unilateral facial weakness
- Small mouth, chin, and side areas of the nose tip
- Palatal abnormalities (Cleft lip and/or palate for example)
Clinical Management
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- It is important that the immune problems in infants are identified early so that special precautions may be implemented regarding immunization and blood transfusions
- Most treatment is directed at alleviating symptoms, infections are treated aggressively with antibiotics
- Patients may undergo cardiac surgery for their heart abnormalities
- Hypoparathyroidism causing hypocalcemia is often transient, but may require lifelong vitamin D treatment
- Thymus transplantation can be used to address absence of the thymus in complete DiGeorge syndrome