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°Childrens Hospital Bambino Gesù - University of Tor Vergata, Rome, Italy. Clinical features of children with 22q.11 deletion Syndrome. Preliminary report.

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Presentation on theme: "°Childrens Hospital Bambino Gesù - University of Tor Vergata, Rome, Italy. Clinical features of children with 22q.11 deletion Syndrome. Preliminary report."— Presentation transcript:

1 °Childrens Hospital Bambino Gesù - University of Tor Vergata, Rome, Italy. Clinical features of children with 22q.11 deletion Syndrome. Preliminary report of AIEOP Cancrini C, Puliafito P, Di Gilio MC, Finocchi A, Soresina A, Martino S, Pignata C, Aiuti A, Ugazio AG, Rossi P, Plebani A, for the Italian Network for Primary Imunodeficiencies. Ospedale Pediatrico Bambino Gesù ISTITUTO DI RICOVERO E CURA A CARATTERE SCIENTIFICO DIPARTIMENTO DI MEDICINA PEDIATRICA DISCUSSION AND CONCLUSION Our preliminary results confirm that the presenting feature is usually a congenital cardiac defect (tab) and that a high risk of delay of diagnosis exist in children presenting mild or not cardiac involvement. Indeed, in the 17% of patients diagnosis was delayed. Pediatricians have to be awared that diagnosis is often delayed and that other clinical features leading to the diagnosis as speech language impairment, development delay, recurrent infections could be the clinical manifestations raising the suspect of del22. Dysmorphic features are always present but it is reported in a variable percentage depending on several clinical observators. Although a very small proportion of patients had a severe immunodeficiency, recurrent infections were present in the 51% of patients diagnosed later; so this could be the symptom leading to the diagnosis. T cell values were decreased as already reported but it is not predictive of infections. Interestingly, we also observed humoral defects in some patients, as several studies recently reported. Moreover autoimmune diseases have been observed in 22 patients. Interestingly one patient had a mono-articular arthritis while chronic polyarticular arthritis has been reported more frequently in del22. Larger and prospective studies could contribute to identify immunological parameters that influence the development of infections and autoimmune diseases. In conclusion, we evidence a delay of diagnosis in children without cardiac defects or severe symptoms and we believe that many patients are still undiagnosed. Furthemore, these patients are followed by different specialists that might not always understand the complexity of this condition. The application of the protocol could provide an increase knowledge among pediatricians and specialist reducing the delay of diagnosis and favouring a correct management of these patients. Because of the wide clinical spectrum, only an interdisciplinary team of experts in long term follow-up will warrant optimal care in these patients. We thank all the patients and their families, the Italian association of del 22 Aidel, the Associazione Immunodeficienze Primitive (AIP). ENROLLMENT CRITERIA All male and female patients of any age with deletion 22 are eligibile. FISH for del22 is recommended for all patients that present at least two of the following clinical aspects 1. Congenital heart desease 2. Palatal anomalies 3. Neonatal hypocalcemia 4. Immunodeficiency and/or autoimmune disease 5. Facial dysmorphism RESULTS At September 2006 we enrolled 100 patients (55 males and 45 females). The median age at diagnosis, was 5 months (range: 0-216 months). In 79% patients the diagnosis was made during the first 2 years of age. In this group, cardiac defects and neonatal hypocalcemia were the most relevant clinical features leading to diagnosis. In the remaining 21 patients, diagnosed after 2 years of age, speech language impairment, development delay, recurrent infections, associated to dysmorphic features, were the clinical manifestations raising the suspect of del22. Recurrent infections were present in 43% of patients and autoimmune manifestations were present in 23% of patients. One patient presents SCID with no T cells and has been Thymus transplanted. Immunological evaluation at diagnosis, available for 85 patients, showed a decreased number of CD3+ T-cell in 62 patients (73%). Molecular investigation by FISH has been performed in 49 patients parents; interestingly in 3 cases mothers were healthy carriers for del22. Two patients died for cardiovascular complications and 1 for a severe autoimmune anemia and thromocytopenia. INTRODUCTION In may 2005, we proposed to adopt in the context of the Italian network for Primary Immunodeficiencies – AIEOP, a Protocol to be applied in patients with 22q 11 deletion syndrome. The aim was to investigate the presenting phenotype at the diagnosis and to better define the natural history. This could provide guidelines for the selection of patients that must be rapidly investigate by genetic test and for a better and earlier interdisciplinary management of these patients. Torino 27 Brescia 7 1 Milano 33 Roma Padova 20 9 Napoli 3 Palermo 100 PATIENTS AIM OF THE STUDY Define and apply uniform assistential recommendations in all the national territory. Provide to all patients common diagnostic and therapeutic recommendations Value the natural history of each case following the eterogeneity of the clinical aspects. Improve the quality of life. TABLES 0-2096 446-1844 694-2503 576-1468 268-1829 210-840 1600-4000 1800-4000 1400-4300 1300-3400 700-2200 650-1500 1-2821 654-3101 975-3448 961-2734 647-3256 378-2204 2500-5500 2500-5600 1900-5900 2100-6200 1400-3700 1200-2600 0-797 198-2288 173-1231 117-1093245-1025 168-1440 560-1700 590-1600 500-1700 620-2000 490-1300 370-1100 GRAPHICS: limphocyte subsets (CD3+, CD4+, CD8+) BIBLIOGRAPHY Digilio Mc, Angioni A, De Santis M, Lombardo Et Al. Spectrum of clinical variability in familial deletion 22q11.2: from full manifestation to extremely mild clinical anomalies, Clin Genet, 2003 Apr;63(4):308-13 BOTTO LD, MAY K, FERNHOFF PM, CORREA A, COLEMAN K, RASMUSSEN SA, MERRITT RK, O'LEARY LA, WONG LY, ELIXSON EM, MAHLE WT, CAMPBELL RM. A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population. 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FELTRI, M.A. DE IORIS, A. ANGIONI, B. DALLAPICCOLA. Anatomic patterns of conotruncal defects associated with deletion 22q11.Genetics in Medicine 2001;3(1):45-48 M. PIERDOMINICI, F. MAZZETTA, E. CAPRINI, M. MARZIALI, M.C. DIGILIO, B. MARINO, A. AIUTI, F.AMATI, G. RUSSO, G. NOVELLI, F. PANDOLFI, G. LUZI, A. GIOVANNETTI. Biased T-cell receptor repertoires in patients with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Clin Exp Immunol 2003;132:323-31 Romiti ML, Cancrini C, Castelli-Gattinara G, Di Cesare S, Ciaffi P, Bernardi S, Rossi De Gaspari M, Halapi E, Rossi P. Kinetics of the T-cell receptor CD4 and CD8 V repertoire in HIV-1 vertically infected infants early treated. AIDS 2001, 15: 2075-2084; Pelkonen P. et al, 2002. Chronic arthritis associated with chromosome deletion 22q11.2 syndrome Oskarsdottir S. et al, 2004 Presenting phenotype in 100 children with the 22q11 deletion syndrome.


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