April 2019 By PsychDB.com

DiGeorge (22q11.2 Deletion) Syndrome

DiGeorge Syndrome (also known as 22q11.2 Deletion Syndrome, and formerly Velocardiofacial Syndrome) is a syndrome caused by the deletion of a small segment (microdeletion) of chromosome 22. It is the most common microdeletion syndrome in humans. This microdeletion is also responsible for a 20 to 30 times increased risk for schizophrenia, which equates to 1 in 4 individuals developing schizophrenia. In addition, individuals often have congenital heart problems, facial dysmorphia, developmental delay, learning problems, and cleft palate. Renal impairment, hearing loss, infections, and autoimmune disorders are also common.

Epidemiology

DiGeorge syndrome has a prevalence of 1 in 4,000 people.[1] Individuals are also at a higher risk for early-onset Parkinson's Disease.

What the Heck Does 22q11.2 Mean?

The '22q11.2' in 22q11.2 Deletion Syndrome refers to (see Figure 1):
  • 22: Chromosome 22
  • q: the long arm (“queue”) of the chromosome 22
    • All chromosomes have a short (“petite” or “p”) arm and a long (“queue” or “q”) arm
  • 11.2: the location on chromosome 22 (region (1), band (1), sub-band (2))

22q11.2 Deletion Figure 1

The diagnosis of DiGeorge Syndrome can be confirmed with various methods of genetic testing, including whole genome array, SNP clinical microarray, comparative genomic hybridization, and Multiplex Ligation-dependent Probe Amplification (MLPA). Fluorescence In Situ Hybridization (FISH) studies can also find the deletion in most patients. Cytogenetic (chromosome) testing can also be performed.

In practice, a clinical microarray (CMA) is now considered to be a first-line test for individuals with developmental delay who have multiple congenital abnormalities. The diagnostic yield is around 10-20%. However, there are limitations in that it will not detect all genetic conditions.

The presentation of schizophrenia in individuals with DiGeorge Syndrome is indistinguishable from idiopathic forms of schizophrenia. There is a similar age of onset and prodromal symptoms. Therefore, current guidelines also recommend the same treatment, including with antipsychotics.[2] However, since these patients are at a baseline higher risk of obesity (even without antipsychotic use), there needs to be even more careful monitoring and prevention of metabolic side effects.[3]

Antipsychotics Can Mask Early-Onset Parkinson's Symptoms in DiGeorge + Schizophrenia Patients

Individuals with DiGeorge have a higher risk for early-onset Parkinson's Disease.[4] As a result, individuals with concomitant schizophrenia and on long-term antipsychotic treatment may have their emerging Parkinson's symptoms masked and mistakenly attributed as extrapyramidal symptoms.

The microdeletion in DiGeorge Syndrome is a new mutation (de novo) in almost 90% of cases.[5] There is a highly variable expression with incomplete penetrance.

  • Ionized calcium and PTH should be measured routinely (especially when there are major biological stressors such as a serious medical illness or surgery)[6]
  • TSH (annually)[7]

Patients with DiGeorge have complex needs and often require multidisciplinary teams. Clinical practice guidelines have recommended a various investigations and follow ups.[8][9]

Supplementation

Patients should have daily Vitamin D and calcium supplementation.[10][11]