UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Frequency and phenotypic spectrum of KMT2B dystonia in childhood: A single-center cohort study

Carecchio, M; Invernizzi, F; Gonzàlez-Latapi, P; Panteghini, C; Zorzi, G; Romito, L; Leuzzi, V; ... Nardocci, N; + view all (2019) Frequency and phenotypic spectrum of KMT2B dystonia in childhood: A single-center cohort study. Movement Disorders 10.1002/mds.27771. (In press).

[img] Text
Kurian_Carecchio et al_KMT2B_2018_MDJ_R2_plain.pdf - Accepted version
Access restricted to UCL open access staff

Download (555kB)

Abstract

BACKGROUND: Childhood-onset dystonia is often genetically determined. Recently, KMT2B variants have been recognized as an important cause of childhood-onset dystonia. OBJECTIVE: To define the frequency of KMT2B mutations in a cohort of dystonic patients aged <18 years at onset, the associated clinical and radiological phenotype, and the natural history of disease. METHODS: Whole-exome sequencing or customized gene panels were used to screen a cohort of 65 patients who had previously tested negative for all other known dystonia-associated genes. RESULTS: We identified 14 patients (21.5%) carrying KMT2B variants, of which 1 was classified as a variant of unknown significance. We also identified 2 additional patients carrying pathogenic mutations in GNAO1 and ATM. Overall, we established a definitive genetic diagnosis in 23% of cases. We observed a spectrum of clinical manifestations in KMT2B variant carriers, ranging from generalized dystonia to short stature or intellectual disability alone, even within the same family. In 78.5% of cases, dystonia involved the lower limbs at onset, with later caudocranial generalization. Eight patients underwent pallidal DBS with a median decrease of Burke-Fahn-Marsden Dystonia Rating Scale-Motor score of 38.5% in the long term. We also report on 4 asymptomatic carriers, suggesting that some KMT2B mutations may be associated with incomplete disease penetrance. CONCLUSIONS: KMT2B mutations are frequent in childhood-onset dystonia and cause a complex neurodevelopmental syndrome, often featuring growth retardation and intellectual disability as additional phenotypic features. A dramatic and long-lasting response to DBS is characteristic of DYT-KMT2B dystonia. © 2019 International Parkinson and Movement Disorder Society.

Type: Article
Title: Frequency and phenotypic spectrum of KMT2B dystonia in childhood: A single-center cohort study
Location: United States
DOI: 10.1002/mds.27771
Publisher version: http://doi.org/10.1002/mds.27771
Language: English
Keywords: KMT2B, DBS, WES, childhood, dystonia
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10076827
Downloads since deposit
1Download
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item