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Kabuki syndrome: clinical and molecular diagnosis in the first year of life
  1. Maria Lisa Dentici1,
  2. Alessandra Di Pede2,
  3. Francesca Romana Lepri3,
  4. Maria Gnazzo3,
  5. Mary Haywood Lombardi2,
  6. Cinzia Auriti2,
  7. Stefano Petrocchi3,
  8. Elisa Pisaneschi3,
  9. Emanuele Bellacchio4,
  10. Rossella Capolino1,
  11. Annabella Braguglia2,
  12. Adriano Angioni3,
  13. Andrea Dotta2,
  14. Maria Cristina Digilio1,
  15. Bruno Dallapiccola4
  1. 1Medical Genetics Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
  2. 2Neonatal Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
  3. 3Cytogenetics and Molecular Genetics Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
  4. 4Scientific Directory, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
  1. Correspondence to Dr Maria Lisa Dentici, Medical Genetics Department, Bambino Gesù Pediatric Hospital, Piazza S.Onofrio 4, Rome 00165, Italy; marialisa.dentici{at}


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.

  • Dysmorphology
  • Neonatology
  • Congenital Abnorm
  • Genetics
  • Multidisciplinary team-care

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