title: Kabuki syndrome: clinical and molecular diagnosis in the first year of life.
abstract: OBJECTIVE
  To review the clinical and molecular genetic characteristics of 16 patients presenting a suspected diagnosis of Kabuki syndrome (KS) in the first year of life, to evaluate the clinical handles leading to a prompt diagnosis of KS in newborns. Clinical diagnosis of KS can be challenging during the first year of life, as many diagnostic features become evident only in subsequent years.
  
  
  METHODS
  All patients were clinically investigated by trained clinical geneticists. A literature review was performed using the Pubmed online database and diagnostic criteria suggested by DYSCERNE-Kabuki Syndrome Guidelines (2010) were used (a European Network of Centres of Expertise for Dysmorphology, funded by the European Commission Executive Agency for Health and Consumers (DG Sanco), Project 2006122). Molecular analysis of the known causative genes of KS, KMT2D/MLL2 and KDM6A, was performed through MiSeq-targeted sequencing platform. All mutations identified were validated by Sanger sequencing protocols.
  
  
  RESULTS
  Mutations in KMT2D gene were identified in 10/16 (62%) of the patients, whereas none of the patients had KDM6A mutations. Facial dysmorphisms (94%), feeding difficulties (100%) and hypotonia (100%) suggested the clinical diagnosis of KS. No significative differences in terms of facial features were noticed between mutation positive and negative patients of the cohort. Brachydactyly, joint laxity and nail dysplasia were present in about 80% of the patients. Other congenital anomalies were most commonly present in the mutated group of patients, including left-sided cardiac abnormalities, skeletal, renal and anorectal malformations and hypertricosis.
  
  
  CONCLUSIONS
  We present an overview of patients with KS diagnosed during the first year of life. Early diagnosis is serviceable in terms of clinical management and for targeted genetic counselling.
authors.affiliation: Medical Genetics Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Maria Lisa
authors.initials: ML
authors.lastname: Dentici
authors.affiliation: Neonatal Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Di Pede
authors.affiliation: Cytogenetics and Molecular Genetics Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Lepri
authors.affiliation: Cytogenetics and Molecular Genetics Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Gnazzo
authors.affiliation: Neonatal Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Mary Haywood
authors.initials: MH
authors.lastname: Lombardi
authors.affiliation: Neonatal Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Auriti
authors.affiliation: Cytogenetics and Molecular Genetics Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Petrocchi
authors.affiliation: Cytogenetics and Molecular Genetics Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Pisaneschi
authors.affiliation: Scientific Directory, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Bellacchio
authors.affiliation: Medical Genetics Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Capolino
authors.affiliation: Neonatal Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Annabella
authors.initials: A
authors.lastname: Braguglia
authors.affiliation: Cytogenetics and Molecular Genetics Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Angioni
authors.affiliation: Neonatal Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Dotta
authors.affiliation: Medical Genetics Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Digilio
authors.affiliation: Scientific Directory, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005145:Face / Q000002:abnormalities*; D005260:Female; D006402:Hematologic Diseases / Q000175:diagnosis* / Q000235:genetics; D056466:Histone Demethylases / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D025202:Molecular Diagnostic Techniques; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D015837:Vestibular Diseases / Q000175:diagnosis* / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C120898:KMT2D protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D056466:Histone Demethylases; C523998:KDM6A protein, human
keywords: Congenital Abnorm; Dysmorphology; Genetics; Multidisciplinary team-care; Neonatology