Academic Learning Profiles Across Disorders of KMT2 Gene Family: Superimposed and Distinct Features Across Kabuki, Wiedemann-Steiner and ODLURO Syndromes.

Objectives: Kabuki syndrome (KS), Wiedemann-Steiner syndrome (WSS) and O'Donnell-Luria-Rodan (ODLURO) syndrome are rare disorders caused by pathogenic variants in histone lysine methyltransferases, specifically the KMT2 gene family. All of these disorders are commonly associated with intellectual disability. Recent studies found overlap between KS and WSS cognitive phenotypes, suggesting shared disease pathogenesis. In contrast, the neuropsychological profile of ODLURO remains largely unknown. This study examines the academic learning concerns across the syndromes to better understand their cognitive profiles and provide guidance for clinical care.

Methods: Fifty caregivers participated in this study, 25 with a child with WSS (Mean age = 12.85 years, SD = 1.82), 14 with KS (Mean age = 12.06, SD = 5.91) and 11 with ODLURO (Mean age = 12.43, SD = 4.69). All caregivers completed the Colorado Learning Difficulties Questionnaire, a parent-screening inventory of learning/academic challenges, specifically in reading, math and spatial skills.

Results: Results suggest shared deficits in spatial skills, but different patterns of academic learning concerns across syndromes. Those with WSS were rated to show unique challenges in math and spatial domains, while those with ODLURO show global difficulties across areas. Individuals with KS were rated to show the most significant challenges in spatial skills, but comparable reading and math concerns.

Conclusions: Study results support recent publications on the overlapping cognitive profile in WSS and KS, specifically with distinct deficits in visual spatial processing. In contrast, ODLURO is associated with more generalised cognitive difficulties that warrant further investigation. Disruption of KMT2 genes may have common and individual effects on neurodevelopment that necessitate cross-syndrome research to illuminate gene-brain-behaviour relationships.