title: Clinical features and follow-up in patients with 22q11.2 deletion syndrome.
abstract: OBJECTIVE
  To investigate the clinical manifestations at diagnosis and during follow-up in patients with 22q11.2 deletion syndrome to better define the natural history of the disease.
  
  
  METHODS
  A retrospective and prospective multicenter study was conducted with 228 patients in the context of the Italian Network for Primary Immunodeficiencies. Clinical diagnosis was confirmed by cytogenetic or molecular analysis.
  
  
  RESULTS
  The cohort consisted of 112 males and 116 females; median age at diagnosis was 4 months (range 0 to 36 years 10 months). The diagnosis was made before 2 years of age in 71% of patients, predominantly related to the presence of heart anomalies and neonatal hypocalcemia. In patients diagnosed after 2 years of age, clinical features such as speech and language impairment, developmental delay, minor cardiac defects, recurrent infections, and facial features were the main elements leading to diagnosis. During follow-up (available for 172 patients), the frequency of autoimmune manifestations (P = .015) and speech disorders (P = .002) increased. After a median follow-up of 43 months, the survival probability was 0.92 at 15 years from diagnosis.
  
  
  CONCLUSIONS
  Our data show a delay in the diagnosis of 22q11.2 deletion syndrome with noncardiac symptoms. This study provides guidelines for pediatricians and specialists for early identification of cases that can be confirmed by genetic testing, which would permit the provision of appropriate clinical management.
authors.affiliation: University Department of Pediatrics, Bambino Gesù Children's Hospital and Tor Vergata University, Rome, Italy. Electronic address: Cancrini@med.uniroma2.it.
authors.forename: Caterina
authors.initials: C
authors.lastname: Cancrini
authors.affiliation: University Department of Pediatrics, Bambino Gesù Children's Hospital and Tor Vergata University, Rome, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Puliafito
authors.affiliation: Department of Medical Genetics, Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Digilio
authors.affiliation: Pediatrics Clinic and Institute of Molecular Medicine "A. Nocivelli," University and Spedali Civili, Brescia, Italy.
authors.forename: Annarosa
authors.initials: A
authors.lastname: Soresina
authors.affiliation: Department of Pediatrics, University of Turin, Turin, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.affiliation: Department of Pediatrics, University of Bologna, Bologna, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Rondelli
authors.affiliation: Department of Pediatrics and Reproductive Medicine, University of Pisa, Pisa, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Consolini
authors.affiliation: Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Padua, Padua, Italy.
authors.forename: Ezia Maria
authors.initials: EM
authors.lastname: Ruga
authors.affiliation: Department of Allergy and Pulmonology, Pediatric Hospital Giovanni XXIII, University of Bari, Bari, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Cardinale
authors.affiliation: University Department of Pediatrics, Bambino Gesù Children's Hospital and Tor Vergata University, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Finocchi
authors.affiliation: University Department of Pediatrics, Bambino Gesù Children's Hospital and Tor Vergata University, Rome, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Romiti
authors.affiliation: Department of Pediatrics "Federico Vecchio" and Department of Biomedicine of the Development Age, University of Bari, Bari, Italy.
authors.forename: Baldassarre
authors.initials: B
authors.lastname: Martire
authors.affiliation: Pediatric Immunology San Raffaele Telethon Institute for Gene Therapy (TIGET), San Raffaele Hospital, Milan, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Bacchetta
authors.affiliation: Department of Pediatrics, Salesi Hospital, Ancona, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Albano
authors.affiliation: Department of Pediatric Cardiac Surgery, Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Carotti
authors.affiliation: Department of Pediatrics, University of Bologna, Bologna, Italy.
authors.forename: Fernando
authors.initials: F
authors.lastname: Specchia
authors.affiliation: Department of Pediatrics, University of Turin, Turin, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Montin
authors.affiliation: Department of Pediatrics, "Federico II" University of Naples, Naples, Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Cirillo
authors.affiliation: Department of Pediatrics and Neonatology, University of Bologna, Bologna, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Cocchi
authors.affiliation: Department of Pediatric Oncology and Hematology, G. Di Cristina Children's Hospital, Palermo, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Trizzino
authors.affiliation: Department of Pediatrics IRCCS San Matteo Hospital Foundation, Pavia, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Bossi
authors.affiliation: Department of Pediatrics, Division of Pediatric Cardiology, University of Padua Medical School, Padua, Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Milanesi
authors.affiliation: Department of Pediatrics, Anna Meyer Children's Hospital, University of Florence, Florence, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Azzari
authors.affiliation: Department of Pediatrics, University of Palermo, Palerno, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corsello
authors.affiliation: Department of Pediatrics, "Federico II" University of Naples, Naples, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Pignata
authors.affiliation: University Department of Pediatrics, Bambino Gesù Children's Hospital and Tor Vergata University, Rome, Italy; Pediatric Immunology San Raffaele Telethon Institute for Gene Therapy (TIGET), San Raffaele Hospital, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Aiuti
authors.affiliation: Department of Pediatrics, Ca' Granda IRCCS Foundation, University of Milan, Milan, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Pietrogrande
authors.affiliation: Department of Pediatrics, "La Sapienza" University, Rome, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Marino
authors.affiliation: Division of Rheumatology, Department of Pediatrics, Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Alberto Giovanni
authors.initials: AG
authors.lastname: Ugazio
authors.affiliation: Pediatrics Clinic and Institute of Molecular Medicine "A. Nocivelli," University and Spedali Civili, Brescia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.affiliation: University Department of Pediatrics, Bambino Gesù Children's Hospital and Tor Vergata University, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Rossi
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000453:epidemiology; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D057210:Delayed Diagnosis; D002658:Developmental Disabilities / Q000175:diagnosis / Q000453:epidemiology*; D004062:DiGeorge Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008991:Monitoring, Physiologic / Q000379:methods*; D011446:Prospective Studies; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors; D013997:Time Factors; D055815:Young Adult