Disease relevance of VCF

• Deletions of chromosome 22q11 have been seen in association with DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS) [1].
• Deletions were rare among patients lacking typical DiGeorge syndrome (DGS) or velocardiofacial (VCF) dysmorphic features, and more common in tetralogy of Fallot with pulmonary atresia than tetralogy of Fallot alone [2].
• It would also be advisable that children with isolated CTD should be carefully examined to detect the other morphologic abnormalities of DGA and VCFS, or CATCH 22 (cardiac defects, abnormal facies, thymic hypoplasia/aplasia, cleft palate, hypocalcemia, and 22q11 deletion) [3].
• There was no difference in chamber size and systolic shortening in the two groups, but peak normalized lengthening rate [endocardial (+) VCF] was less than normal in the group with hypertrophy (4.8 +/- 1.4 and 3.1 +/- 0.9 sec-1, respectively, p less than .05) [4].
• Earlier prolapse after tilt was due to a decrease in the end-diastolic diameter from 5.03 +/- 0.74 to 4.50 +/- 0.68 cm (P less than 0.001) with no change in max VCF [5].

Psychiatry related information on VCF

• This expression pattern is consistent with GSCL having either an indirect role in the development of neural crest-derived structures or a direct role in a subset of the phenotype observed in DGS/VCFS, such as learning disorders or psychiatric disease [6].
• BACKGROUND: As children with velocardiofacial syndrome (VCFS) develop, they are at increased risk for psychopathology; one third will eventually develop schizophrenia [7].
• METHODS: Twenty-eight children with VCFS and 29 age- and cognitively matched control subjects received a standardized assessment of childhood psychiatric disorders and behaviors measured by the Child Behavior Checklist (CBCL) [8].
• Methylphenidate treatment for attention-deficit/hyperactivity disorder in children and adolescents with velocardiofacial syndrome: an open-label study [9].
• METHOD: Forty subjects of mean +/- SD age 11.0 +/- 5.0 years with VCFS were assessed for DSM-IV diagnoses using the Schedule for Affective Disorders and Schizophrenia for School-Aged Children, Present and Lifetime Version, and its extended ADHD module (K-SADS-P-ADHD) [9].

High impact information on VCF

• We present preliminary data that velocardiofacial syndrome patients have similar chromosome deletions, a finding consistent with the hypothesis that these disorders represent part of a spectrum of abnormalities seen with monosomy for 22q11 [10].
• Research into the chromosome 22 deletion (del22q11) syndrome, which encompasses DiGeorge and velocardiofacial syndrome, has taken a different path in recent years, using mouse models to circumvent the paucity of informative human material [11].
• CONTEXT: Velocardiofacial syndrome is associated with interstitial deletions of chromosome 22q11, mild to borderline learning disability, characteristic dysmorphology, and a high prevalence of schizophrenia [12].
• RESULTS: People with velocardiofacial syndrome and schizophrenia, compared with both controls and nonschizophrenic patients with velocardiofacial syndrome, had a significant (P<.05) reduction in volume of whole-brain (white + gray) matter and whole-brain white matter, and an increase in total and sulcal cerebrospinal fluid volume [12].
• To assess the potential contribution of 22q11 genes to cognitive and psychiatric phenotypes, we determined the CNS expression of 32 mouse orthologs of 22q11 genes, primarily in the 1.5-Mb minimal critical region consistently deleted in VCFS [13].

Chemical compound and disease context of VCF

• Immediately after amyl nitrite, earlier prolapse was due to an increase of VCF in the preprolapse period, with max VCF increasing from 2.15 +/- 0.27 to 3.06 +/- 0.40 circ/sec (P less than 0.001), there being no change in the end-diastolic diameter up to this time [5].
• Comparison of stress ventriculograms before and after surgery in six patients with predominant AS (isoproterenol infusion, 0.3 microgram per kilogram of body weight per minute) showed an increase of EF, VCF, and MNSER and a decrease of PSWS [14].
• 4 The effects of acebutolol differed in patients with ischaemic heart disease compared with normals in that LVEDP and EDV increased, mean VCF decreased and cardiac output was lowered more [15].
• We feel that pathologists should be familiar with isotretinoin embryopathy and its pathogenesis in order to assist in differentiating this syndrome from other genetic syndromes that involve branchial arch defects, such as DiGeorge syndrome or velocardiofacial syndrome [16].

Biological context of VCF

• We conclude that FISH is an efficient and direct method for the detection of 22q11 deletions in subjects with features of DGS and VCFS as well as in pregnancies at high risk for a deletion [1].
• Using probes and cosmids from the DiGeorge critical region (DGCR), deletions of 22q11 were detected in 83% of DGS and 68% of VCFS patients by DNA dosage analysis, fluorescence in situ hybridisation, or by both methods [1].
• The present performed a molecular analysis in one family including a patient with clinical diagnosis of VCFS and his sister with a suggestive phenotype [17].
• Recurrent 22q11.2 deletion in a sibship suggestive of parental germline mosaicism in velocardiofacial syndrome [17].
• Partial monosomy 10p is a rare chromosomal condition and a significant proportion of patients show features of DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS) [18].

Anatomical context of VCF

• Because many of the tissues and structures affected in VCFS/DGS derive from the pharyngeal arches of the developing embryo, it is believed that haploinsufficiency of a gene(s) involved in embryonic development may be responsible for its etiology [19].
• T cell receptor repertoire and function in patients with DiGeorge syndrome and velocardiofacial syndrome [20].
• We therefore investigated TCR Vbeta families in lymphocytes isolated from blood and thymic samples of seven patients with DGS and seven patients with VCFS, all with 22q11.2 deletion [20].
• Contractibility of the myocardium was also examined by measurement of the ejection fraction (EF), percentage of the shortening of the left ventricle (%FS), and average velocity of the circumferential shortening of the muscular fibers (VCF) [21].
• Visceral and subcutaneous fat (VCF and SCF) areas were determined by abdominal computed tomography (CT) scan [22].

Associations of VCF with chemical compounds

• An acute increase in afterload produced by angiotensin in 8 pts (44% increase in peak stress) led to a 38% decrease in VCF, a 2.5% increase in max dP/dt, no significant change in (dP/dt)/C, a 26% reduction in (dP/dt)/CP, variable responses in peak VCE and Vmax, an 11% increase in VCEDP10 and minor changes in (dP/dt)/DP40 [23].
• Compared to the normals, the adriamycin group had a fall in VCF and a rise in fractional shortening and ejection fraction, together with a rise in end-systolic diameter [24].
• From 1980 to 1982, 79 patients (group B) received induction chemotherapy, Adriamycin, vincristine, cyclophosphamide, methotrexate, and 5-FU (AVCMF) and RT on a cyclical schedule and VCF maintenance [25].
• After ouabain infusion, all indices of LV contractility: dP/dt, VCF, and ejection fraction rose significantly in the normal group, while LV filling pressure and end-diastolic volume remained unchanged [26].
• In all, propranolol caused small reductions in heart rate and peak VCF [27].

Enzymatic interactions of VCF

• The gene encoding a cationic amino acid transporter (SLC7A4) maps to the region deleted in the velocardiofacial syndrome [28].

Other interactions of VCF

• Combined with our previously reported patients, deletions have been detected in 88% of DGS and 76% of VCFS patients [1].
• A critical haploinsufficiency region for DGS/VCFS was defined on 10p (DGCR2) [18].
• Cloning, genomic organization, and chromosomal localization of human citrate transport protein to the DiGeorge/velocardiofacial syndrome minimal critical region [29].
• The patient with the 10p deletion had facial features consistent with VCFS, plus sensorineural hearing loss, and renal anomalies [30].
• One of these is its biochemical function in metabolism of catecholamine neurotransmitters; another is the microdeletion, on chromosome 22q11, that includes the COMT gene and causes velocardiofacial syndrome, a syndrome associated with a high rate of psychosis, particularly schizophrenia [31].

Analytical, diagnostic and therapeutic context of VCF

• Fluorescence in situ hybridization (FISH) using the DiGeorge chromosome region (DGCR) probe (Oncor) was used to detect 31 deletions in 100 patients with possible VCFS [32].
• There were, however, no obvious pathognomonic findings for the differential diagnosis between CTAF and VCF [33].
• Sequence analysis of the putative promoter and the coding region of GSCL was performed on the DNA template from 17 VCFS patients who did not have a detectable 22q11 deletion to identify mutations [19].
• Prader Willi/Angelman and DiGeorge/velocardiofacial syndrome deletions: diagnosis by primed in situ labeling (PRINS) [34].
• Fractional shortening and ejection fraction did not change significantly, but hemodialysis slightly increased mean VCF from 1.2 +/- 0.1 s-1 to 1.4 +/- 0.1s-1 (p less than 0.005) [35].

References