Velocardiofacial syndrome (VCFS), also known as digeorge syndrome or 22q11.2 syndrome, is a genetic disorder characterized by malformations in the pharyngeal arch derivatives including the thymus, parathyroid glands, and the conotruncal part of the heart.
VCFS presents with a myriad of anomalies and clinical features which occur in different combinations in patients. Some features may present later in life, while others present at birth.
Generally, the signs and symptoms which manifest in each patient are reflective of the anomalies present; cardiac defects such as tetralogy of fallot present with cyanosis, and abnormal interruptions in the aortic arch presents with poor feeding, lethargy, tachypnea, and cardiogenic shock. Poor feeding and failure to thrive may result secondary to severe cardiac anomalies and congestive cardiac failure.
Other common cardiac defects seen in VFCS include ventricular septal defects, pulmonary atresia, truncus arteriosus, absent pulmonary valve syndrome, aortic stenosis, and abnormalities of the pulmonary artery. Generally, the defects affect the cardiac outflow tract. Abnormalities in the aortic arch are almost a typical finding in VFCS and are strongly suggestive of the 22q11.2 microdeletion. Cardiac defects are seen in three of four cases of VFCS.
The palatal abnormality predisposes to recurrent upper respiratory tract and ear infections which exacerbate the speech difficulty. Pierre robin syndrome is seen in 15-20% of cases and it comprises of micrognathia, glossoptosis, and cleft palate.
Delay in attaining developmental milestones is also commonly seen in infants, up to 55% of which develop attention deficit hyperactivity disorder (ADHD) in childhood.
Over 10% of children go on to develop psychiatric disorders including schizophrenia with antisocial personality disorders. Hypocalcemia from the parathyroid defects may cause seizures during infancy. The hypocalcemia may resolve spontaneously.
About 30% of patients with VFCS have short stature, 25-50% of whom are below the second percentile with respect to all growth parameters for the respective age . Common facial features in VFCS include micrognathia, malar flattening, and a bulb shaped tip of the nose.
Infants with congenital cardiac anomalies such as interrupted aortic arch type B or other aortic arch malformations and great vessel anomalies should undergo genetic testing for the 22q11.2 microdeletion. This can be carried out by using the fluorescence in situ hybridization (FISH) method. This deletion is seen in over 95% of patients with VFCS. However, those cases in which this typical microdeletion is not detected, more advanced gene testing techniques such as comparative genomic hybridization (MLPA) may be employed to detect smaller gene mutations in the same region.
Mosaicism in which not all cells are affected by the mutation can also occur in VFCS. Patients exhibiting mosaicism may present with no symptoms at all. Generally, all parents whose children have this deletion detected in all or some cells should undergo genetic testing. Furthermore, all newborns diagnosed with VFCS should have their serum calcium levels checked and monitored. This is also recommended in any child with seizures in whom VFCS is suspected.
Immunological investigations such as T-cell marker analysis may be necessary to determine and monitor the immune status.
Once a diagnosis is made, investigations for serious anomalies such as cardiac defects should be commenced. Heart failure, immune deficiency, feeding difficulties, and failure to thrive can all be addressed with medical care.
Generally, VFCS requires a long-term multidisciplinary management approach involving a team comprising clinical psychologist, geneticist, genetic counsellor, physical therapist, plastic surgeon, pediatric immunologist, otorhinolaryngologist, and cardiac surgeon.
Management for infants and preschoolers is usually centered on correcting feeding difficulties and developmental delays, however, in children of school age, treatment is centered on cognitive and behavioral improvement. Common cognitive impairments associated with VFCS include diminished mathematical skills, visuospatial and executive impairments.
About 10% of children with VFCS develop severe personality and psychiatric disorders .
VCFS may cause significant impairment in the quality of life of the patient because of the plethora of anomalies present. Hearing defects, speech difficulties, learning disabilities, feeding difficulties, spinal deformities, and immune compromise play significant roles in reducing the quality of life of the patient. Other factors which could worsen the prognosis of this syndrome are the secondary ophthalmic, renal, cardiac, and psychiatric problems.
The most cases of velocardiofacial syndrome occur as a result of a microdeletion at the locus q11.2 of the short arm of chromosome 22, caused by mainly due to imbalance during the translocation between the pair of chromosome 22.
In approximately 10% of the patients, this deletion is inherited from a parent while in the other 90% cases it is acquired by mutation spontaneously. This microdeletion is detectable in 95% of patients with VFCS.
Velocardiofacial Syndrome is the most prevalent syndrome found associated with cleft palate. It is also the commonest syndrome caused by microdeletions and the second most prevalent syndrome found associated with congenital cardiac defects.
VCFS is seen in approximately 1 child out of 2,000 - 5,000 live births. However, there are varying statistics which vary according to the mode of data collection and method of verification of the diagnosis. In most studies, the reports of the diagnosis depended on birth records, neonatal examinations, or other unverified sources  .
There is a possibility of under-diagnosis of this condition since many features become apparent much later in life or even might go undetected. Severe complications include cardiac malformations which may occur in about 70% of VCFS cases.
VCFS is caused by a microdeletion at the 11.2 band or locus of the short arm of chromosome 22. This in turn impairs the development and migration of neural crest cells, and development of the bronchial arches.
In about 90% of cases, the microdeletion is a new deletion occurring as a de-novo deletion or translocation involving 3-megabase in a region that contains at least 40 genes . Because these genes are involved in the development of the heart and structures in the central nervous system, a number of coronary artery defects occur in this syndrome .
In the other 10% of cases, the mutation is inherited in an autosomal dominant pattern from a parent. Inheritance of this genetic mutation occurs in 50% of cases.
This genetic mutation is commonly associated with aortic arch, aortic branch, or pulmonary vessel defects, therefore, necessitating genetic testing in these patients . However in this syndrome, there is a wide spectrum of features which may present in different combinations among patients, even of the same families   .
There is a 50% chance of transferring the mutated chromosome from a parent to an offspring. Therefore, genetic testing and counselling is recommended for parents with children with suspected or confirmed VFCS.
Antenatal ultrasonography may be necessary to determine the severity or complexity of VFCS in a fetus. Antenatal cardiac imaging of the fetus may also assist in determining the degree of cardiac malformation in the fetus. Most of the severe cardiac defects can be identified in fetus enabling appropriate decision by the doctor and parents about the continuation of pregnancy and treatment after birth.
Care should be taken in immunizing children with VFCS. Due to the possibility of immune compromise and lymphocyte dysfunction, such patients should not undergo immunization with live vaccines. To prevent secondary seizures, preoperative and postoperative serum calcium should be monitored in affected children.
All possible organs prone to defects in VFCS should be assessed and investigated for presence of abnormalities before any clinical procedure is undertaken to prevent secondary complications.
Velocardiofacial syndrome (VCFS) is a genetic disorder involving microdeletion of the 11.2 band of the short arm of chromosome 22. VCFS was first described by Shprintzen and his colleagues in 1978 .
The disorder presents with an array of congenital malformations affecting virtually every organ system in the body. It includes over 180 clinical features which may not be similar in all patients: typical abnormalities include cleft palate, cardiac defects, and a characteristic facies. Patients are often affected by speech defects, cognitive and developmental impairments, and psychiatric disorders .
Cardiac defects are found in approximately 75% of cases of VFCS and mainly involve the outflow portion of developing heart. The commonest cardiac defects in VFCS are interrupted aortic arch seen in up to 50% of cases, involvement of truncus arteriosus, and tetralogy of fallot. Other common defects include aortic stenosis and pulmonary artery abnormalities .
Diagnosis of VFCS involves genetic testing and investigations to determine the presence of major complications such as heart defects and immunosuppression.
Treatment of VFCS involves a multidisciplinary approach involving geneticists, genetic counsellors, pediatric cardiologists and cardiac surgeons, pediatric immunologists, plastic surgeons, and speech therapists.
Velocardiofacial syndrome (VCFS) is also known as digeorge syndrome or 22q11.2 syndrome. It is a genetic condition caused by a removal or deletion of a small part of chromosome 22. It presents with many malformations affecting virtually all the organs of the body.
There are 23 pairs of chromosomes in each cell of the body. In VFCS, there is a removal of a section of the short arm of the 22nd pair of chromosomes. This section contains genes which code for the formation of several structures including parts of the heart and contents of the head. Therefore this change (mutation) in the genes causes abnormalities in the body structures for which the absent genes are coded. In few cases, this genetic mutation is transferred from one parent to the offspring, although there is a 50% chance of that happening .
This syndrome is estimated to occur in one out of 2,000 to 5,000 births. This syndrome presents with a wide range of abnormalities. Whereas some of these abnormalities may occur from birth, others may not manifest till the child is older.
VFCS typically presents with abnormal shapes of structures in the face; with cleft palate, a term for incomplete fusion of the palate causing feeding problems. The syndrome is also associated with an abnormally small jaw, abnormal round shape of the tip of the nose, abnormal structure of the heart and blood vessels taking blood away from the heart.
The heart defects are particularly of concern because they may cause poor feeding, stunted growth, and poor mental abilities. Heart defects occur in every three out of four patients with VFCS. A few of the children with VFCS usually progress to developing serious psychiatric and personality disorders. Children with VFCS are also very prone to convulsions.
The eye may also be affected in patients with VFCS causing cataracts in both eyes and abnormalities in the blood vessels in the eye. Generally, affected children have speech problems, learning difficulties, behavioral abnormalities and also weak immune system.
This syndrome may be diagnosed by physical examination of the child. However, the diagnosis can be confirmed by using certain techniques to detect the genetic abnormalities within the cells. Other investigations to check for possible severe malformations such as heart defects are necessary one the diagnosis for VFCS is confirmed.
The treatment of this syndrome involves a team approach. Specialists from different medical fields - geneticists, genetic counsellors, heart surgeons, ear, nose and throat specialists, plastic surgeons, and physical and speech therapists - all work in concert for a very long duration for the treatment and management of the patient.
For the parents of any child in whom VFCS is suspected or has been confirmed, genetic counselling and testing is recommended to help in future pregnancies.