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.