Graves' disease in DiGeorge syndrome: patient report with a review of endocrine autoimmunity associated with 22q11.2 deletion
ABSTRACT DiGeorge syndrome, which falls within a wider phenotypic spectrum associated with deletions of 22q11.2, is associated with a number of endocrine disorders. These include hypoparathyroidism, hypothyroidism and growth hormone deficiency. We report an unusual case of autoimmune hyperthyroidism (Graves' disease) presenting in a 3 year-old male with DiGeorge syndrome. The development of endocrine specific autoimmune disease in a syndrome associated with immune deficiency and the spectrum of endocrine autoimmunity associated with deletions of 22q11.2 are described. Paediatricians and patients with 22q11.2 deletions should be particularly aware of the risks of developing disorders of thyroid function.
- SourceAvailable from: Claudio Pignata
[Show abstract] [Hide abstract]
- "For example, AIRE expression in the thymus requires cross-talk between developing thymocytes and stromal cells, and this process is dependent on an organized thymic microenvironment  . A higher incidence of autoimmune phenomena, including autoimmune cytopenias   autoimmune arthritis , and autoimmune endocrinopathies , can be observed in DiGeorge syndrome (DGS)   in which abnormal thymic development may result in impaired expression of AIRE and, potentially, of other transcription factors that regulate expression of organ-specific antigens in the thymus resulting in defective central tolerance  . However, it should be mentioned that in DGS autoimmunity may also be explained by exaggerated chronic inflammatory responses, " bystander " activation of autoreactive T cells and " molecular mimicry " . "
ABSTRACT: The thymus is a specialized organ that provides an inductive environment for the development of T cells from multipotent hematopoietic progenitors. Self-nonself discrimination plays a key role in inducing a productive immunity and in preventing autoimmune reactions. Tolerance represents a state of immunologic nonresponsiveness in the presence of a particular antigen. The immune system becomes tolerant to self-antigens through the two main processes, central and peripheral tolerance. Central tolerance takes place within the thymus and represents the mechanism by which T cells binding with high avidity self-antigens, which are potentially autoreactive, are eliminated through so-called negative selection. This process is mostly mediated by medullary thymic epithelia cells (mTECs) and medullary dendritic cells (DCs). A remarkable event in the process is the expression of tissue-specific antigens (TSA) by mTECs driven by the transcription factor autoimmune regulator (AIRE). Mutations in this gene result in autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), a rare autosomal recessive disease (OMIM 240300). Thus far, this syndrome is the paradigm of a genetically determined failure of central tolerance and autoimmunty. Patients with APECED have a variable pattern of autoimmune reactions, involving different endocrine and nonendocrine organs. However, although APECED is a monogenic disorder, it is characterized by a wide variability of the clinical expression, thus implying a further role for disease-modifying genes and environmental factors in the pathogenesis. Studies on this polyreactive autoimmune syndrome contributed enormously to unraveling several issues of the molecular basis of autoimmunity. This review focuses on the developmental, functional, and molecular events governing central tolerance and on the clinical implication of its failure.International Reviews Of Immunology 10/2012; 31(5):344-62. DOI:10.3109/08830185.2012.697230 · 5.28 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: La calcémie est une valeur biologique finement régulée. Ces dernières années, de nombreuses études fondamentales ainsi que la mise en évidence d’anomalies moléculaires responsables de certaines maladies héréditaires du métabolisme phosphocalcique ont permis de mieux connaître l’ensemble des acteurs de cette régulation, de l’embryogénèse des glandes parathyroïdiennes à la valeur de calcémie dosée. La recherche ciblée de certaines de ces anomalies génétiques sera utile non seulement pour le clinicien mais surtout pour le patient, pour la démarche étiologique, le suivi évolutif et thérapeutique ainsi que pour un éventuel diagnostic anténatal. Les principales anomalies génétiques pouvant être étudiées sont les suivantes : gènes CaSR, GNAS, AIRE, VDR, ADN mitochondrial, délétion en 22q11.Serum calcium is a fine-tuned biological value. In recent years, fundamental research and study of molecular anomalies causing certain hereditary diseases of phosphocalcium metabolism have greatly contributed to our knowledge of the factors involved in this regulation, from the embryogenesis of the parathyroid glands to the assay value of serum calcium. Targeted research on these genetic anomalies would be useful not only for the clinician, but also for the patient, contributing to the etiological search, patient follow-up, and possibly to antenatal diagnosis. The main genetic anomalies identified to date are: CaSR, GNAS, AIRE, VDR, mitochondrial DNA, 22q11 deletion.Annales d Endocrinologie 06/2005; 66(3):207-215. DOI:10.1016/S0003-4266(05)81752-4 · 0.66 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The understanding of velo-cardio-facial syndrome has grown markedly since the initial descriptions of this common genetic disorder nearly 30 years ago. Our knowledge of the syndrome has advanced in part from opportunities to monitor many patients into adulthood because of advances in the fields of cardiothoracic surgery and immunology. Longitudinal study has brought to light psychiatric and behavioral features of the syndrome that are often not apparent until late adolescence or the early adult years. Certain endocrine and immunologic features of the syndrome thought to be resolved in childhood are now witnessed in older patients. Variable expression and lack of disease awareness are two major factors that contribute to the delays in diagnosis in many cases. To address this, there has been a call to delineate screening parameters for patients at risk of carrying the deletion. Several areas are highlighted in this review, reflecting the focus of scholarly work on velo-cardio-facial syndrome in the past year. Molecular genetics has shown smaller deletions in many families with the syndrome. The gene TBX1 has been found to be important to the phenotype. Surgical outcomes data reveal the greater challenges involved in correcting velopharyngeal insufficiency. Defining the genetic basis of velo-cardio-facial syndrome will allow clinicians and basic scientists to make further inroads into understanding the variable expressivity of this syndrome. It is also important to be aware of the continued diagnostic challenges encountered by clinicians in attempts to improve the detection of patients with this syndrome.Current Opinion in Otolaryngology & Head and Neck Surgery 01/2006; 13(6):371-5. DOI:10.1097/01.moo.0000186203.53214.ac · 1.39 Impact Factor