Description, Causes and Risk Factors:
Alternative Name: Shprintzen syndrome, Sedlackova syndrome, DiGeorge syndrome, Conotruncal anomaly face syndrome.
Velocardiofacial Syndrome is a genetic disorder with varying conditions present in each individual with the syndrome. However, conditions that are common to the syndrome include certain heart defects, effects on facial appearance, and lack of or underdeveloped thymus and parathyroid glands. It is also the most common known genetic risk factor for schizophrenia. It is estimated to occur in one in 3,000 to 4,000 live births.
It is caused by the deletion of a small piece of chromosome 22 at the q11 region. In about 10 percent of families, the deletion is inherited and other family members are affected or at risk for passing this deletion to their children. The gene is autosomal dominant, therefore, any person who has this deletion has a 50 percent chance of passing the deletion to a child. For this reason, whenever a deletion is diagnosed, both parents are offered the opportunity to have their blood studied to look for this deletion.
The large majority of individuals with VCFS have a deletion of three million base pairs containing dozens of genes. The challenge has been to determine how much of the extensive phenotype can be traced back to one or more of these genes.
Many investigators also believe that deletion of the gene TBX1 is responsible for the cardiac and vascular findings and perhaps other anomalies traced to the neural crest. Other genes have also been implicated in the anomalies found in VCFS, including DGCR8 and HIRA. It has also been reported that a regulatory effect that accounts for malformations in VCFS is the inactivation of TGFß signaling in the neural crest stem cells. The mechanism of spontaneous rearrangements at 22q11.2, originally described several years ago, was confirmed in another study demonstrating a recombination error in stage 1 of meiosis. The unique arrangement of 22q11.2 that makes it a hot spot for rearrangement has been traced as an evolutionary change in the structure of human DNA.
Learning disorders are nearly ubiquitous in the syndrome, and immune disorders, speech and language impairment, and behavioral abnormalities occur in most cases. Therefore, essentially every case with VCFS will present to pediatricians with multiple problems. The recent literature reflects much of this variability of clinical presentation, although there has been little emphasis on treatment.
Immune deficiency is not among the most common anomalies in VCFS, but the problem is one of the most difficult to contend with for affected individuals and their families. Reports on immunologic and associated endocrine disorders have covered the age spectrum, from the neonatal period to adult life.
General symptoms may include:
Reduced immunity to infection.
Behavioral differences, such as attentiondeficits and autism.
Hearing and vision problems.
Facial Features May Include:
Cleft lip and/or palate.
Asymmetric crying facies.
Small mouth, chin, and side areas of the nose tip.
Small ears with squared upper ear.
Psychological symptoms may include:
Learning and memory disabilities.
Emotional abnormalities (flat affect and poorsocial interaction).
High incidence for schizophrenia and/orbipolar disorder in adult (30% VCFS patientsdevelop schizophrenia).
Psychomotor and perceptual deficits.
Symptoms may include:
Conotruncal heart defects (e.g., tetralogy of Fallot, interrupted aortic arch, ventricular septal defects, vascular rings).
Hearing loss or abnormal ear exams.
Genitourinary anomalies (absent or malformed kidney).
Hypocalcemia (low blood calcium levels).
Microcephaly (small head).
Mental retardation (usually borderline to mild).
IQs are generally in the 70 to 90 range.
Psychiatric disorders in adults (e.g., schizophrenia, bipolar disorder).
Severe immunologic dysfunction (an immune system which does not work properly due to abnormal T-cells, causing frequent infections).
Palatal abnormalities (such as cleft lip and/or palate).
In addition to a prenatal history, complete medical and family history, and a physical examination, diagnostic procedures for VCFS may include:
X-ray - a diagnostic test which uses invisible electromagnetic energy beams to produce images of internal tissues, bones, and organs onto film.
Echocardiography - a procedure that evaluates the structure and function of the heart by using sound waves recorded on an electronic sensor that produce a moving picture of the heart and heart valves.
Fluorescence In Situ Hybridization (FISH) studies - when features of conotruncal heart defects, clefting, other facial features, hypocalcemia, and absent thymus are identified, a blood test is usually ordered to look for a deletion in the chromosome 22q11.2 region. FISH is specifically designed to look for small groups of genes that are deleted. If the FISH test finds no deletion in the 22q11.2 region and the features of VCFS are still strongly suggestive, then a full chromosome study is usually performed to look for other chromosome defects that have been associated with this syndrome.If a 22q11.2 deletion is detected in a child, then both parents are offered the FISH test to see if this deletion is inherited.
Blood tests and tests to examine for immune system problems.
Treatment will also depend on the particular features in any given child and may include the following:
A plastic surgeon and a speech pathologist will evaluate cleft lip and/or palate.
Speech and gastrointestinal specialists will evaluate feeding difficulties.
Immunology evaluations should be performed in all children with this deletion. To monitor T-cell disorder and recurrent infections, live viral vaccines should be avoided and all blood products for transfusions (if needed) should be irradiated unless cleared by an immunology physician.
In severe cases where immune system function is absent, bone marrow transplantation is required.
Heart defects will be evaluated by a cardiologist.
Depending on the presence and severity of various features, any child with VCFS might need one or more of the following surgeries:
Repair of cleft palate.
Repair / reconstruction of the lower jaw.
Reconstructive surgery of the ears.
Repair of heart defects (see list of specific congenital heart defects).
NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.
DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.
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