1
Second Department of Neurology, Faculty of Medicine, Comenius University, University Hospital Bratislava, Bratislava, Slovakia
,
Silvia Radová
2
Department of Pediatric Neurology, Faculty of Medicine, Comenius University, University Hospital Bratislava National Institute of Children's Diseases, Bratislava, Slovakia
,
Miriam Kolníková
2
Department of Pediatric Neurology, Faculty of Medicine, Comenius University, University Hospital Bratislava National Institute of Children's Diseases, Bratislava, Slovakia
,
Peter Vlkovič
1
Second Department of Neurology, Faculty of Medicine, Comenius University, University Hospital Bratislava, Bratislava, Slovakia
,
Michael Zech
3
Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany
4
Institute of Human Genetics, School of Medicine, Technical University of Munich, Munich, Germany
› Author AffiliationsFunding M.Z. receives research support from the German Research Foundation (grant no.: DFG 458949627; ZE 1213/2-1).
ASXL3 loss-of-function variants represent a well-established cause of Bainbridge–Ropers syndrome, a syndromic neurodevelopmental disorder with intellectual and motor disabilities. Although a recent large-scale genomics-based study has suggested an association between ASXL3 variation and cerebral palsy, there have been no detailed case descriptions. We report, here, a female individual with a de novo pathogenic c.1210C > T, p.Gln404* nonsense variant in ASXL3, identified within the frame of an ongoing research project applying trio whole-exome sequencing to the diagnosis of dystonic cerebral palsy. The patient presented with a mixture of infantile-onset limb/trunk dystonic postures and secondarily evolving distal spastic contractures, in addition to more typical features of ASXL3-related diseases such as severe feeding issues, intellectual disability, speech impairment, and facial dysmorphic abnormalities. Our case study confirms a role for ASXL3 pathogenic variants in the etiology of cerebral-palsy phenotypes and indicates that dystonic features can be part of the clinical spectrum in Bainbridge–Ropers syndrome. ASXL3 should be added to target-gene lists used for molecular evaluation of cerebral palsy.
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