Unique profile of academic learning difficulties in Wiedemann-Steiner syndrome

R Ng; H T Bjornsson; J A Fahrner; J Harris

doi:10.1111/jir.12993

Unique profile of academic learning difficulties in Wiedemann-Steiner syndrome

J Intellect Disabil Res. 2023 Feb;67(2):101-111. doi: 10.1111/jir.12993. Epub 2022 Nov 27.

Authors

R Ng^{1

2}, H T Bjornsson^{3

4

5

6}, J A Fahrner^{3

4}, J Harris^{1

3

4

7}

Affiliations

¹ Kennedy Krieger Institute, MD, Baltimore, USA.
² Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
⁶ Department of Genetics and Molecular Medicine, Landspitali University Hospital, Reykjavik, Iceland.
⁷ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

Background: Wiedemann-Steiner syndrome (WSS) is a rare genetic disorder caused by heterozygous variants in KMT2A. To date, the cognitive profile associated with WSS remains largely unknown, although emergent case series implicate increased risk of non-verbal reasoning and visual processing deficits. This study examines the academic and learning concerns associated with WSS based on a parent-report screening measure.

Participants and methods: A total of 25 parents of children/adults with a molecularly-confirmed diagnosis of WSS (mean age = 12.85 years, SD = 7.82) completed the Colorado Learning Difficulties Questionnaire (CLDQ), a parent-screening measure of learning and academic difficulties. Parent ratings were compared to those from a normative community sample to determine focal areas in Math, Reading and Spatial skills that may be weaker within this clinical population.

Results: On average, parent ratings on the Math (mean Z = -3.08, SD = 0.87) and Spatial scales (mean Z = -2.52, SD = 0.85) were significantly more elevated than that of Reading (mean Z = -1.31, SD = 1.46) (Wilcoxon sign rank test Z < -3.83, P < 0.001), reflecting relatively more challenges observed in these areas. Distribution of parent ratings in Math items largely reflect a positively skewed distribution with most endorsing over three standard deviations below a community sample. In contrast, distributions of parent ratings in Reading and Spatial domains were more symmetric but flat. Ratings for Reading items yielded much larger variance than the other two domains, reflecting a wider range of performance variability.

Conclusions: Parent ratings on the CLDQ suggest more difficulties with Math and Spatial skills among those with WSS within group and relative to a community sample. Study results are consistent with recent case reports on the neuropsychological profile associated with WSS and with Kabuki syndrome, which is caused by variants in the related gene KMT2D. Findings lend support for overlapping cognitive patterns across syndromes, implicating potential common disease pathogenesis.

Keywords: KMT2A; Wiedemann-Steiner syndrome; genetics/genetic disorders; learning disorders; math; spatial processing.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Abnormalities, Multiple* / genetics
Adolescent
Child
Child, Preschool
Cognition
Growth Disorders
Humans
Intellectual Disability* / epidemiology
Intellectual Disability* / genetics

Supplementary concepts

Growth Deficiency and Mental Retardation with Facial Dysmorphism
Wiedemann Grosse Dibbern syndrome

Abstract

Publication types

MeSH terms

Supplementary concepts

Grants and funding