Dataset Information

Natural history of KBG syndrome in a large European cohort.

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

SUBMITTER: Loberti L

PROVIDER: S-EPMC9759332 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Natural history of KBG syndrome in a large European cohort.

Loberti Lorenzo L Bruno Lucia Pia LP Granata Stefania S Doddato Gabriella G Resciniti Sara S Fava Francesca F Carullo Michele M Rahikkala Elisa E Jouret Guillaume G Menke Leonie A LA Lederer Damien D Vrielynck Pascal P Ryba Lukáš L Brunetti-Pierri Nicola N Lasa-Aranzasti Amaia A Cueto-González Anna Maria AM Trujillano Laura L Valenzuela Irene I Tizzano Eduardo F EF Spinelli Alessandro Mauro AM Bruno Irene I Currò Aurora A Stanzial Franco F Benedicenti Francesco F Lopergolo Diego D Santorelli Filippo Maria FM Aristidou Constantia C Tanteles George A GA Maystadt Isabelle I Tkemaladze Tinatin T Reimand Tiia T Lokke Helen H Õunap Katrin K Haanpää Maria K MK Holubová Andrea A Zoubková Veronika V Schwarz Martin M Žordania Riina R Muru Kai K Roht Laura L Tihveräinen Annika A Teek Rita R Thomson Ulvi U Atallah Isis I Superti-Furga Andrea A Buoni Sabrina S Canitano Roberto R Scandurra Valeria V Rossetti Annalisa A Grosso Salvatore S Battini Roberta R Baldassarri Margherita M Mencarelli Maria Antonietta MA Rizzo Caterina Lo CL Bruttini Mirella M Mari Francesca F Ariani Francesca F Renieri Alessandra A Pinto Anna Maria AM

Human molecular genetics 20221201 24

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 of a European collaborative study, we collected the largest cohort of KBGS patients (49). A combined array- based Comparative Genomic Hybridization and next generation sequencing (NGS) approach investigated both genomic Copy N ...[more]

PMID: 35861666

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Natural history of KBG syndrome in a large European cohort.

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Natural history of KBG syndrome in a large European cohort.

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