# Handbook of Genetic Counseling/22q11 Deletion Syndrome

22q11 Deletion Syndrome (a.k.a. Velocardiofacial Syndrome (VCF), DiGeorge Syndrome)

## Diagnosis

* Caused by a deletion of material from one copy of the long arm of
chromosome 22
** Submicroscopic deletion in DiGeorge Chromosomal Region
(DGCR)
** Chromosome banding may sometimes detect deletion
** FISH testing detects deletion in 95% of affected individuals
* Autosomal dominant inheritance
** About 94% of patients have de novo mutation
** Parents of affected individuals should have FISH testing
*** Offspring of affected individual have 50% chance of inheriting 22q11 deletion
*** Recurrence risk for siblings of affected individual is very small if FISH testing shows the parents do not have the deletion
* Several genes are located within the DGCR
** Some of these gene products have been identified
** Cannot predict genotype-phenotype correlation because size of
deletion does not seem to correlate with severity of characteristics Characteristic Findings:
* Congenital heart disease
** Found in about 74% of affected individuals
** Usually conotruncal malformations
*** Teratology of Fallot
*** Interrupted aortic arch
*** Truncus arteriasis
*** Ventricular septal defect (VSD)
** Conotruncal malformations identified in infancy/early childhood
and can be surgically repaired
** Mild problems with the aorta may not be recognized
* Palatal abnormalitites
** Found in about 69% of affected individuals
** Several types of abnormalities observed
*** Velopharyngeal incompetence (VPI)
*** Submucosal cleft palate
*** Visible cleft palate
*** Cleft lip and palate
*** Bifid uvulae
** May be surgically repaired
** May affect speech development
** Speech therapy is recommended
* Feeding difficulties
** Found in about 30% of affected individuals
** May be due to palate or heart problems
** May also be caused by problems transporting food from the
mouth to the esophagus
** Signs of feeding difficulty
*** Infants are irritable, gag, vomit, have a weak suck
*** Younger children find spoon feeding easier but have trouble drinking from a cup
*** Older children have difficulty with lumpy, crunchy foods
** May be treated by teaching children better feeding practices
* Immunodeficiency
** Caused by small or missing thymus gland
** Causes greatest number of problems in first year of life
** Children may have frequent infections such as bronchitis or
pneumonia
** As children grow older, T cell production improves
* Hypoparathyroidism
** Regulates calcium levels in bloodstream
*** Absence or underdevelopment leads to hypocalcemia
*** May cause tremors, seizures, muscle spasms, abnormal breathing, and abnormal heart rhythms
** Diagnosed by a blood test
** Treated with calcium supplements
* Growth hormone deficiency
** Approximately 41% of affected individuals are below the 5th
percentile in height
** May be caused by abnormalities in formation of pituitary gland
*** In only about 1/10 of individuals with 22q11 deletion
*** Causes reduced levels of growth factors
** Can be determined with a blood test
** Treatment with injections of growth hormones
* Characteristic Facial Features
** Nose - bulbous nasal tip, prominent nasal root, nasal dimple
** Ear - overfolded helices; cupped, microtic, and protuberant ears;
narrow external auditory meati
** Eyes - hooding of upper or lower lid, ptosis, epicanthal folds
* Renal anomalies
** Found in about 37% of affected individuals
** Includes single kidney, echogenic kidney, small kidneys, and other
renal anomalies
* Juvenile rheumatiod arthiritis (JRA)
** About 150 times more frequent than in general population
** Age of onset is 17 months to 5 years
* Developmental difficulties
** Found in 70-90% of affected individuals
** Development of motor skills
*** Due to problems with muscle strength and coordination
*** Often delayed in sitting, crawling, walking
*** May be helped by physical therapy
* Learning
** Typically have slower learning rate
** Follow same learning sequence as other children but at slower pace
** Often have strong verbal skills but weaker math skills
** May have difficulty paying attention
** Early diagnosis and intervention important
** May require learning support
* Speech and language
** Verbal speech usually does not develop until 2-3 years
** May also have difficulty in formation of sounds
** Palatal problems often lead speech problems
** Early intervention by speech and language pathologist is important
* Behavioral difficulties
** About 40% of affected individuals develop psychiatric illness
*** Depression
*** Anxiety
*** Schizophrenia
*** Bipolar disorders
** May be evident as tantrums and mood swings in childhood
** Social skills training and counseling may be necessary

## Resources

* Cincinnati Velocardiofacial Support Group
    Teresa Paul
    9327 Bluewing Terrace
    Cincinnati, Ohio 45236
    Email: MOTHERTP@aol.com
* Velo-Cardio-Facial Syndrome Education Foundation
    Jacobson hall Room 707
    University Hospital
    750 East AdamsStreet
    Syracuse, NY 13210
    Phone: 315-464-6590
    Email: vcfsef@hscsyr.edu
    Web:
* International DiGeorge/VCF Support Network
    c/o Family Vioces of New York
    461/2 Clinton Avenue
    Cortland, NY 13045
    Phone: 607-753-1621 (day) 607-753-1250 (evening)
* Chromosome Deletion Outreach, Inc.
    PO Box 724
    Boca Raton, FL 33429-0724
    Phone: 561-395-4252
    Email: cdo@worldnet.att.net
    Web:

## References

* The Children's Hospital of Philadelphia. Faces of Sunshine: The 22q11.2 Deletion.
* NIH Gene Clinics web site:
* OMIM:
* Smith's. Shprintzen Syndrome.

## Notes

The information in this outline was last updated in 2002.