Management of Gastrointestinal Comorbidities Improves Behavioral Symptoms in a Patient with Kleefstra Syndrome

Abstract Kleefstra Syndrome (KS) is a neurodevelopmental disorder with multisystem involvement, characterized by developmental delay, intellectual disability, hypotonia, and limited or absent speech. Additional psychiatric comorbidities, including aggression and self-injurious behavior (SIB), have been reported in a subset of patients. This individual, a 19-year-old female with KS, demonstrated severe aggression and SIB that were poorly responsive to usual behavioral medications, including atypical antipsychotics. Over an eight-year period, she required two urgent care visits, five emergency room visits, and two neurobehavioral inpatient unit (NBIU) admissions for acute psychiatric stabilization. Behavioral escalations complicated routine daily care. Coincident gastrointestinal (GI) symptoms—including constipation, hematemesis, and decreased appetite—were noted intermittently but not initially pursued. However, after several episodes of hematemesis during an NBIU admission prompted further investigation, she was found to have reflux esophagitis, rectal inflammation, and megacolon. Following treatment of these conditions, the individual demonstrated a marked reduction in aggression, improved social engagement, and no further utilization of the ER or NBIU. Daily behavioral medication dosing has since been tapered, with ongoing plans to transition to as needed use. This patient’s trajectory highlights the importance of evaluating somatic contributors to behavioral escalation in complex patients with significant language impairment.