Abstract
OBJECTIVES: Wiedemann-Steiner syndrome (WSS) is a rare Mendelian disorder of the epigenetic machinery caused by heterozygous pathogenic variants in KMT2A. Currently, the specific neurocognitive profile of this syndrome remains unknown. This case series provides insight into the cognitive phenotype of WSS.
METHODS: This study involves a retrospective medical chart review of 10 pediatric patients, each with a molecularly confirmed diagnosis of WSS who underwent clinical neuropsychological evaluation at an academic medical center.
RESULTS: The majority of patients performed in the below average to very low ranges in Nonverbal Reasoning, Visual/Spatial Perception, Visuoconstruction, Visual Memory, Attention, Working Memory and Math Computation skills. In contrast, over half the sample performed within normal limits on Receptive Vocabulary, Verbal Memory, and Word Reading. Wilcoxon signed rank test showed weaker Nonverbal versus Verbal Reasoning skills (p = .005). Most caregivers reported deficits in executive functioning, most notably in emotion regulation.
CONCLUSIONS: Nonverbal reasoning/memory, visuospatial/construction, attention, working memory, executive functioning, and math computation skills are areas of weakness among those with WSS. These findings overlap with research on Kabuki syndrome, which is caused by variants in KMT2D, and suggest disruption in the neurogenesis of the hippocampal formation may drive shared pathogenesis of the two syndromes.
| Original language | English |
|---|---|
| Pages (from-to) | 512-518 |
| Number of pages | 7 |
| Journal | Journal of the International Neuropsychological Society : JINS |
| Volume | 29 |
| Issue number | 5 |
| Early online date | 5 Sept 2022 |
| DOIs | |
| Publication status | Published - Jun 2023 |
Bibliographical note
Funding Information: No specific funding was received for this study. However, R.N. would like to acknowledge support from National Institute of Health (NIH)(R25 NS117356). J.H. has support from the National Institute of Child Health and Development (NICHD)(K23HD101646), J.A.F. from The Hartwell Foundation (Individual Biomedical Research Award) and the NIH/NICHD (K08HD086250), and H.T.B. from the Wiedemann-Steiner Syndrome Foundation, Louma G. Foundation, Icelandic Research Fund (195835, 206806, 217988) and Icelandic Technological Development Fund (2010588). Publisher Copyright: Copyright © INS. Published by Cambridge University Press, 2022.Other keywords
- Clinical neuropsychology
- Executive functioning
- Genetic disorders
- Genetics
- Hippocampus
- Visuospatial functioning