Case Report: A novel HNRNPK gene variant causing Au-Kline syndrome; the genotype and phenotype of the oldest individual ever described
This report describes the diagnostic and treatment course of an adult woman with the ultra-rare Au-Kline syndrome (AUKS). Since the age of 32 years, when the syndrome was yet undiagnosed, the patient suffered from behavioral decline coinciding with changes in living conditions. At the age of 38, following a bladder infection, she presented with a delirium for which antipsychotic medication was started. The delirium resolved but, while the medication was continued, the pre-existing behavioral symptoms persisted. Clinicpal genetic evaluation revealed a history of congenital hypotonia, developmental delay, and multiple (craniofacial) dysmorphisms. Subsequent trio-based genetic testing demonstrated a novel pathogenic variant in the HNRNPK gene, causative for AUKS. Clinical neuropsychological assessment showed moderate intellectual disability, slow information processing speed, restricted verbal expression, and limited comprehension. Registration of sensory information was severely hampered and there was difficulty in self-modulating the sensory information to be processed. Contextual adaptations and individual psychomotor therapy were then implemented to optimize sensory and motor information processing, to promote daily functioning, and reduce behavioral decline. These interventions, along with the long-term psychotropic medication, had beneficial effects on her functioning, which subsequently returned to near premorbid levels by the age of 45. Overall, this case underscores that the genetic and neuropsychological identification of a neurodevelopmental disorder, together with the integration of tailored psychomotor interventions and contextual adaptations, can improve psychiatric management and daily functioning, and mitigate behavioral decline in adulthood, even following a prolonged diagnostic delay.