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.
Entire Body System
The main manifestations of our patient were feeding difficulties, respiratory infections, short stature, peculiar face with hypertelorism, prominent nose, abnormal ears, microstomia and crowded teeth, short broad neck and shield chest with pectus deformity [ncbi.nlm.nih.gov]
Learning disabilities occur often; short stature, slender hyperextensible hands and digits, scoliosis, mental retardation, inguinal hernia, auricular abnormalities, and microcephaly occur less frequently. [medical-dictionary.thefreedictionary.com]
Height: short stature was detected in 7 of 73 (9.6%) of the total patients; the patients with short stature were all 10 years old; the height was within the normal age in all adolescent patients. [nature.com]
Less frequent features include short stature, small-than-normal head ( microcephaly ), mental retardation, minor ear anomalies, slender hands and digits, and inguinal hernia. [medicinenet.com]
Complications In the newborn period, patients may present with hypocalcemic tetany/seizures, manifestation of cardiac abnormality, nasal regurgitation, GERD, dysphagia, and recurrent infections. [unboundmedicine.com]
While somatic symptoms include congenital cardiovascular and craniofacial abnormalities, recurrent infections and hypocalcemia1, the most prevalent group of symptoms are neuropsychiatric and include cognitive dysfunction with mild mental retardation, [clinicaltrials.gov]
Sequel to the thymic underdevelopment, there may be immune dysfunction which make the patients prone to recurrent infections and development of autoimmune diseases. [symptoma.com]
People with 22q11.2 deletion syndrome often experience recurrent infections caused by problems with the immune system, and some develop autoimmune disorders such as rheumatoid arthritis and Graves disease in which the immune system attacks the body's [ghr.nlm.nih.gov]
In order to monitor T-Cell disorder and recurrent infections, live viral vaccines should be avoided, and all blood products for needed transfusions should be irradiated, unless cleared by an immunology doctor. [disabled-world.com]
Boys with VCFS scored significantly lower than girls on school functioning (p .05) and cognitive fatigue (p .01). [ncbi.nlm.nih.gov]
Learning disabilities and difficulties Significant feeding difficulties Hypocalcemia Conductive or sensorineural hearing loss Deficiencies in growth hormones Renal anomalies Seizures Psychiatric disorders Weariness or easy fatigue Failure to realize one [syndromepictures.com]
However, the immunodeficiency can last into adult life, with an increased vulnerability to infections and fatigue, as well as increased risk of autoimmune diseases in which the immune system of the body attacks its own cells. [socialstyrelsen.se]
However, it does not correlate with severe T-cell dysfunction and it includes a range of pediatric diseases. [ncbi.nlm.nih.gov]
We at the Children's Hospital of Philadelphia, therefore, refer to all patients with a 22q11.2 deletion by their cytogenetic name, patients with a 22q11.2 deletion (as we do in other chromosomal disorders, i.e. 4p-, 18q , trisomy 21, etc.) which allows [cbil.upenn.edu]
Failure to Thrive
Poor feeding and failure to thrive may result secondary to severe cardiac anomalies and congestive cardiac failure. [symptoma.com]
Congenital anomalies of any organ system, classically cardiac defects, particularly interrupted aortic arch type B, septal defects, tetralogy of Fallot pulmonary atresia, truncus arteriosus, and vascular ring Failure to thrive/dysphagia/gastroesophageal [unboundmedicine.com]
Jaw & Teeth
Additional common traits include feeding problems, developmental delay, microcephaly (small head size) and psychiatric disorders (such as bipolar disorder and schizophrenia). [kidsplasticsurgery.org]
Distinct physical features sometimes associated with the syndrome include loss of muscle tone (hypotonia), small slender stature, tapered hands and fingers, small head circumference (microcephaly), recessed jaw (retrognathia), tubular nose, flat cheeks [rarediseases.org]
What follows are the most common features of Velo-Cardio-Facial syndrome: Feeding Difficulties Microcephaly, or a small head Hearing loss, or abnormal ear exams Hypocalcemia, or low blood calcium levels IQ levels that are usually in the 70 to 90 range [disabled-world.com]
The list includes: cleft palate, usually of the soft palate (the roof of the mouth nearest the throat which is behind the bony palate); heart problems; similar faces (elongated face, almond-shaped eyes, wide nose, small ears); learning difficulties; eye [healthieryou.com]
Typical facial features include a long face, small almond shaped eyes, a wide bridged nose, and malformations of the ear. Learning disabilities, including delayed speech and developmental milestones, are present in 70-90% of individuals. [genedx.com]
[…] problem that is of the conotruncal type such as the interrupted aortic arch, cases of truncus arteriosus and tetralogy of Fallot Palatal problems that predispose the child to difficulties of feeding and speech Similar facial features like having an almond-shaped [syndromespedia.com]
Symptoms include: cleft palate, usually of the soft palate (the roof of the mouth nearest the throat which is behind the bony palate); heart problems; similar faces (elongated face, almond-shaped eyes, wide nose, small ears); eye problems; feeding problems [genome.gov]
Congenital absence of the nasolacrimal duct is a rare condition with only a few cases reported, most of which describe complete bony occlusion at the distal end of the lacrimal sac. [ncbi.nlm.nih.gov]
Low Set Ears
These may include small, low-set ears, short width of eye openings (palpebral fissures), hooded eyes, a relatively long face, an enlarged nose tip (bulbous), or a short or flattened groove in the upper lip. [mayoclinic.org]
Some of the signs of velocardiofacial syndrome are as follows: Abnormalities of the palate like cleft palate Characteristic facial features like a narrow groove of the upper lip, wide-set eyes, hypertelorism or low-set ears. [syndromepictures.com]
Long face with prominent upper jaw Underdeveloped lower jaw Low set ears Prominent nose with narrow nasal passages Thin upper lip with a down-slanted mouth Multiple abnormalities of the heart including ventricular septal defect (VSD), pulmonary atresia [cincinnatichildrens.org]
Patients No. 44 presented with palatal abnormality, immune deficiency, mild mental retardation, low set ears, and conductive hearing disturbance. [journals.plos.org]
A large number of medical conditions may be associated with 22q11.2 deletion syndrome, such as hearing impairment, poor vision, breathing problems, poor kidney function and relatively short stature for one's family. [mayoclinic.org]
Lundin J, Söderhäll C, Lundén L, Hammarsjö A, White I, et al. (2010) 22q11.2 microduplication in two patients with bladder exstrophy and hearing impairment. Eur J Med Genet 53: 61–65. View Article Google Scholar 26. [journals.plos.org]
Some children will require glasses, and children with more severe hearing impairments will need hearing aids. Early contact should be established with a paediatric dental specialist for an assessment. [socialstyrelsen.se]
In each patient, sporadic rolandic or occipital partial-onset seizures with the clinical and electroencephalographic features of benign idiopathic childhood epilepsy manifested at age 3 and 5 years, respectively. [ncbi.nlm.nih.gov]
Hypocalcemia from the parathyroid defects may cause seizures during infancy. The hypocalcemia may resolve spontaneously. [symptoma.com]
Speech and feeding problems Severe oral motor planning Hyper nasal speech Disorganized or dysfunctional feeding patterns 6. [speechsolutionshawaii.com]
A nasal speech tone is observed in the vast majority of individuals with VCFS as well as difficulties with articulation whose origin is assumed to be the cleft palate and pharyngal hypotonia. [cibsr.stanford.edu]
Later in life, VPI leads to slurred pronunciation and often to very open, nasal speech owing to leakage of air up into the nose. Feeding difficulties are frequent. [socialstyrelsen.se]
speech quality; audiology evaluation prior to school enrollment; surveillance for scoliosis; routine dental care; regular speech, language and developmental assessments to provide appropriate remediation. [ncbi.nlm.nih.gov]
Many infants present with generalized hypotonia and delayed milestones. There are psychological consequences with the reduction of full-scale intelligence quotient. [clinicaladvisor.com]
His physical examination showed the characteristic facies of velocardiofacial syndrome as well as dysmetria and dysdiadocho-kinesia consistent with cerebellar degeneration. Molecular cytogenetic studies showed a deletion of 22q11.2. [ncbi.nlm.nih.gov]
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.
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