The variable neuropsychological profile of Diets–Jongmans syndrome: a case series of four family members

OBJECTIVE: Diets-Jongmans syndrome (DIJOS) is a genetic, autosomal dominant condition caused by variation in the KDM3B gene on chromosome 5q31. Intellectual developmental disorder (IDD) is typically described as a key feature of the condition. This case series aimed to characterize the broader neuropsychological profile of DIJOS. METHODS: Four family members with genetically confirmed DIJOS underwent comprehensive neuropsychological assessment. Additional information was obtained through behavioral observations, review of available medical and educational records, and clinical interviews. RESULTS: All individuals presented with distinct cognitive profiles. Scores on intelligence measures for Cases 1-3 (aged 19, 21, and 46) ranged from Below Average to Average, though were predominantly within normative limits. Cases 1-3 displayed intact processing speed and verbal comprehension, weaknesses in working memory and aspects of executive functioning, and variable performance in perceptual reasoning and memory. By contrast, Case 4's (aged 15) data largely ranged from Exceptionally Low to Below Average, consistent with previously diagnosed IDD. All cases presented with learning difficulties, mental health symptoms, and features of autism spectrum disorder and attention-deficit hyperactivity disorder. CONCLUSION: The cognitive profile of DIJOS is more variable than suggested by existing literature, with only 1 of 4 family members meeting DSM-5-TR criteria for IDD. Recognizing the clinical heterogeneity of DIJOS may aid in earlier detection and provision of more individualized supports. Future longitudinal studies will be important for examining the role of genetic as opposed to environmental contributors to clinical presentation and characterizing symptom trajectory across the lifespan.