Natural history of KBG syndrome in a large European cohort

• DOI: 10.1093/hmg/ddac167
• Publication Date: 2022-07-21T14:21:33Z
• Authors: Lorenzo Loberti; Lucia Pia Bruno; Stefania Granata; Gabriella Doddato; Sara Resciniti; Francesca Fava; Michele Carullo; Elisa Rahikkala; Guillaume Jouret; Leonie A Menke; Damien Lederer; Pascal Vrielynck; Lukáš Ryba; Nicola Brunetti-P...; Amaia Lasa-Aranzasti; Anna Maria Cueto-...; Laura Trujillano; Irene Valenzuela; Eduardo F Tizzano; Alessandro Mauro ...; Irene Bruno; Aurora Currò; Franco Stanzial; Francesco Benedic...; Diego Lopergolo; Filippo Maria San...; Constantia Aristidou; George A Tanteles; Isabelle Maystadt; Tinatin Tkemaladze; Tiia Reimand; Helen Lokke; Katrin Õunap; Maria K Haanpää; Andrea Holubová; Veronika Zoubková; Martin Schwarz; Riina Žordania; Kai Muru; Laura Roht; Annika Tihveräinen; Rita Teek; Ulvi Thomson; Isis Atallah; Andrea Superti-Furga; Sabrina Buoni; Roberto Canitano; Valeria Scandurra; Annalisa Rossetti; Salvatore Grosso; Roberta Battini; Margherita Baldas...; Maria Antonietta ...; Caterina Lo Rizzo; Mirella Bruttini; Francesca Mari; Francesca Ariani; Alessandra Renieri; Anna Maria Pinto
• Keywords: Clinodactyly; Brachydactyly

Abstract KBG syndrome (KBGS) is characterized by distinctive facial gestalt, short stature and variable clinical findings. With ageing, some features become more recognizable, allowing a differential diagnosis. We aimed to better characterize natural history of KBGS. In the context European collaborative study, we collected largest cohort KBGS patients (49). A combined array- based Comparative Genomic Hybridization next generation sequencing (NGS) approach investigated both genomic Copy Number Variants SNVs. Intellectual disability (ID) (82%) ranged from mild moderate with severe ID identified in two patients. Epilepsy was present 26.5%. Short consistent over time, while occipitofrontal circumference (median value: −0.88 SD at birth) normalized years. Cerebral anomalies, were 56% thus represented second most relevant feature reinforcing suspicion paediatric age when vertebral/dental anomalies are vague. Macrodontia, oligodontia dental agenesis (53%) almost as frequent skeletal such brachydactyly, fifth finger, finger clinodactyly, pectus excavatum/carinatum, delayed bone age. 28.5% individuals, prenatal ultrasound reported. Except for three splicing variants, leading premature termination, variants all frameshift. Our results, broadening spectrum phenotype progression, provide useful tools facilitate diagnosis improve management. suggest consider wider range before excluding perform careful odontoiatric/ear-nose-throat (ENT) evaluation order look even submucosal palate cleft given high percentage abnormalities. NGS approaches, following evidence antenatal should include ANKRD11.