1/7. Vasomotor instability in neonates with chromosome 22q11 deletion syndrome.Approximately 70% of individuals with chromosome 22q11 deletion syndrome (22q11DS) have congenital heart defects. A host of other vascular problems in these patients, such as tortuous carotid arteries, Raynaud's phenomenon, unexplained hypotension, hypertension, and hypothermia, raise the possibility that there may be abnormal autonomic regulation of the vascular system. So far, however, there has been no formal report of autonomic dysfunction in patients with 22q11 deletion. We present two infants with 22q11DS, who had profound hypotension after uncomplicated surgeries for congenital heart disease. The hypotension was not responsive to vasopressor treatment (and extracorporeal membrane oxygenation in one infant) and resulted in death, due to multiorgan system failure. Obvious causes, such as poor cardiac contractility, prolonged circulatory arrest, neurological abnormality, sepsis and blood loss were excluded. On autopsy, no abnormalities were found that could explain the hypotension. We hypothesize that these infants died of severe hypotension due to abnormal vascular tone and that this is a variable feature in individuals with 22q11 deletion. The autonomic nervous system, which is responsible for the regulation of vasomotor tone, may be variably affected in 22q11DS. This could have implications for the surgical management of patients with 22q11DS. Further studies on this topic would establish or refute the association between 22q11DS and dysautonomia.- - - - - - - - - - ranking = 1keywords = dysfunction (Clic here for more details about this article) |
2/7. digeorge syndrome with isolated aortic coarctation and isolated ventricular septal defect in three sibs with a 22q11 deletion of maternal origin.digeorge syndrome was diagnosed in an infant who had an interrupted aortic arch, hypoparathyroidism, and low T lymphocyte numbers. Two siblings had heart defects that are not commonly described in digeorge syndrome (a membranous ventricular septal defect and coarctation of the aorta respectively). These siblings did not have evidence of thymic dysfunction or hypoparathyroidism. Chromosome analysis showed that the mother, whose cardiovascular examination was normal, and her three offspring with heart defects had a 22q11 interstitial deletion, which was confirmed by molecular analysis. This family suggests that 22q11 deletions can cause apparently isolated heart defects and that the range of these defects may be wider than previously recognised. Once the genes that are deleted in this family are characterised they will be useful candidate genes in the investigation of isolated cardiac malformations.- - - - - - - - - - ranking = 1keywords = dysfunction (Clic here for more details about this article) |
3/7. Di George anomaly and velocardiofacial syndrome.The velocardiofacial syndrome is an autosomal dominant disorder characterized by cleft palate, cardiac anomalies, characteristic facies, and learning disabilities. The Di George anomaly involves developmental defects of the third and fourth pharyngeal pouches, resulting in thymic and parathyroid hypoplasia and cardiac defects. The cases of individuals in two families help substantiate the notion that the Di George anomaly occurs as a feature of the velocardiofacial syndrome. The proband in family 1 was a male infant with persistent hypocalcemia and cardiac defects consisting of truncus arteriosus, atrial septal defect, ventricular septal defect, and abnormal aortic arch vessels. autopsy revealed absence of thymic and parathyroid tissue, and the Di George anomaly was diagnosed. His father had a submucous cleft palate, T cell dysfunction, and facial features consistent with the velocardiofacial syndrome. This is the third case of male-to-male transmission of velocardiofacial syndrome. The proband of family 2 was a 4-year-old girl with developmental delay, persistent neonatal hypocalcemia, ventricular septal defect, T cell dysfunction, and facial features of the velocardiofacial syndrome. The Di George anomaly has been reported to occur in at least 18 different disorders. The observation that the Di George anomaly is a component manifestation of the velocardiofacial syndrome in these two families provides further evidence that the Di George anomaly is not a distinct syndrome of a single origin but rather a heterogeneous developmental field defect. It is proposed that all previously reported cases of autosomal dominant Di George anomaly are examples of the velocardiofacial syndrome.- - - - - - - - - - ranking = 2keywords = dysfunction (Clic here for more details about this article) |
4/7. Facial dysmorphia, parathyroid and thymic dysfunction in the father of a newborn with the DiGeorge complex.A boy born at full-term died after 14 days from cardiac failure. At autopsy DiGeorge complex was diagnosed. The father was found to have facial dysmorphia and hypocalcaemia. Investigations revealed no cause other than hypoparathyroidism associated with normal serum 1,25-dihydroxyvitamin D concentrations and normal renal handling of phosphate. Immunological tests, performed on two occasions with an interval of 9 months, revealed a decrease in the number of CD8 lymphocytes, compatible with a partial thymus deficiency. The combination of facial dysmorphia with dysfunction of the thymus and the parathyroid glands can constitute a partial DiGeorge complex. The findings in this family are compared with reports of four other families with DiGeorge complex in two generations. In genetic counseling DiGeorge complex should be considered a heterogenous disorder. Screening of the parents for somatic stigmata, hypocalcaemia, disturbed cellular immunity, cardiac and chromosomal abnormalities is essential.- - - - - - - - - - ranking = 5keywords = dysfunction (Clic here for more details about this article) |
5/7. Features of di George syndrome in a child with 45,XX,-3,-22, der(3),t(3;22)(p25;q11).A child with an unbalanced translocation resulting in monosomy for chromosomes 22 (q11 pter) and 3(p25 pter) is described. Although no immunological dysfunction could be demonstrated, the abnormalities found are similar to those seen in the di George syndrome which has been associated with monosomy for the same region of chromosome 22.- - - - - - - - - - ranking = 1keywords = dysfunction (Clic here for more details about this article) |
6/7. Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in digeorge syndrome.Immunoglobulin (Ig) genes were isolated from unamplified conventional as well as polymerase chain reaction-generated cDNA libraries constructed from the peripheral blood cells of a patient with complete digeorge syndrome. Comparison of the sequences of 36 heavy chain clones to the recently expanded database of human VH genes permitted identification of the germline VH genes that are expressed in this patient as well as placement of 19 of these genes in a partially resolved 0.8-mb region of the human VH locus. The pattern of VH gene use does not resemble the fetal (early) repertoire. However, as in the fetal repertoire, there are a number of cDNAs derived from germline genes that previously have been identified as autoantibodies. Two D mu sequences also were identified, as was another sequence resulting from a unique recombination event linking JH to an unidentified sequence containing a recombination signal sequence-like heptamer. All of the DiGeorge cDNAs are closely related to germline VH genes, showing little or no evidence of somatic mutation. In contrast, comparably selected IgM VH sequences derived from normal adult and age-matched human libraries, and from a second digeorge syndrome patient in whom the degree of thymic dysfunction is much less severe, exhibit considerable evidence of somatic mutation. The absence of somatic mutation is consistent with the atypical development of functional antibody responses associated with complete digeorge syndrome and implicates a role for T cells in the generation of diversity within the B cell repertoire.- - - - - - - - - - ranking = 1keywords = dysfunction (Clic here for more details about this article) |
7/7. Phenotypic discordance in monozygotic twins with 22q11.2 deletion.We report on male monozygotic twins with 22q11.2 deletion and discordant phenotypes. The twins had twin-to-twin transfusion syndrome. Twin 1, the smaller of the pair, had tetralogy of fallot, a characteristic facial appearance, swallowing dysfunction, anal atresia, short stature, and mental retardation, whereas twin 2 had a characteristic facial appearance but no other signs of the 22q11 deletion syndrome. fluorescence in situ hybridization analysis showed a microdeletion on chromosome 22q11.2 in both twins. Zygosity analysis gave a probability of monozygosity greater than 99.999%. These observations indicate that environmental factors or postzygotic events play a role in the phenotypic variability in the twins.- - - - - - - - - - ranking = 1keywords = dysfunction (Clic here for more details about this article) |