Kabuki syndrome: clinical and molecular diagnosis in the first year of life. Issue 2 (3rd October 2014)

• Record Type: Journal Article
• Authors: Dentici, Maria Lisa; Di Pede, Alessandra; Lepri, Francesca Romana; Gnazzo, Maria; Lombardi, Mary Haywood; Auriti, Cinzia; Petrocchi, Stefano; Pisaneschi, Elisa; Bellacchio, Emanuele; Capolino, Rossella; Braguglia, Annabella; Angioni, Adriano; Dotta, Andrea; Digilio, Maria Cristina; Dallapiccola, Bruno
• Is Part Of: Archives of disease in childhood. Volume 100:Issue 2(2015)
• Page Start: 158
• Page End: 164
• Publication Date: 2014-10-03
• Subjects: Dysmorphology -- Neonatology -- Congenital Abnorm -- Genetics -- Multidisciplinary team-care; Children -- Diseases -- Periodicals; Infants -- Diseases -- Periodicals; 618.920005
• DOI: 10.1136/archdischild-2013-305858
• Languages: English
• ISSNs: 0003-9888

Abstract

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.