We aim to further characterize the neuropsychological and neuropsychiatric profile of Kleefstra Syndrome (KLEFS1) including full scale IQ (FSIQ), psychiatric symptoms, and psychiatric medications used. In doing so, we aim to help anticipate vulnerabilities and provide treatment guidance for comorbid behavioral disturbances.

Kleefstra Syndrome (KLEFS1) is a rare genetic disorder characterized by variable presentations of intellectual disability, autism spectrum disorder, behavioral challenges, hypotonia, distinct facial features, and systemic abnormalities. Neurodevelopmental and neuropsychiatric conditions significantly impact quality of life in these individuals, though these conditions are not well characterized.

We examined clinical data from a retrospective cohort of 85 patients with KLEFS1 seen at Boston Children’s Hospital. We reviewed prior testing to examine FSIQ and related subdomains. We also compiled and harmonized psychiatric symptoms and diagnoses into symptom categories. Similarly compiled psychopharmacological treatments, indications, and efficacy.

21 patients had FSIQ measured, though instruments varied. Mean FSIQ was 63.4, though patients with deletions (45.5) had significantly lower FSIQ than patients with sequence variants (72.3, p < 0.001). The most common psychiatric symptoms observed were aggression/self-injury (20%), anxious symptoms (19%), sleep disruption (16%), inattentive/hyperactive symptoms (16%), and neuropsychiatric regression (16%). Psychoactive medications were most prescribed for sleep disturbances, aggression/irritability, attention, and anxiety, with attentional symptoms being the most treatment-responsive.

While KLEFS1 appears to be marked by intellectual disability, with deletions causing more severe deficits than sequence variants. Psychiatric disturbances including aggression, inattention/hyperactivity, anxiety, and sleep disturbances are common with variability in treatment response.