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: [1]

• 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: [2]

References

• The Children's Hospital of Philadelphia. Faces of Sunshine: The 22q11.2 Deletion.
• NIH Gene Clinics web site: [3]
• OMIM: [4]
• Smith's. Shprintzen Syndrome.

Notes

The information in this outline was last updated in 2002.