Quantifying behaviors of children with Sanfilippo syndrome: the Sanfilippo Behavior Rating Scale

Abstract

The Sanfilippo Behavior Rating Scale (SBRS), a 68 item questionnaire, has been developed to assess the behavioral phenotype of children with Sanfilippo syndrome and its progression over time. Fifteen scales rate orality, movement/activity, attention/self-control, emotional function including anger and fear, and social interaction. Items within scales intercorrelate; measures of internal consistency are adequate. Twelve scales are grouped into 4 abnormality clusters: Movement, Lack of fear, Social/emotional and Executive Dysfunction. A Loess age-trajectory analysis showed that Lack of Fear, Social/Emotional and Executive Dysfunction increased steadily with age; Orality and Mood/Anger/Aggression leveled off. Movement peaked around 6years, then declined as children's excessive/purposeless actions stopped. Compared with standard scales, SBRS Movement was appropriately associated with the Vineland Motor scale; SBRS Lack of Fear had significant associations with the Autism Diagnostic Observation Schedule (ADOS), indicating a symptom overlap between Sanfilippo syndrome and autism. This suggests that reduced fearfulness may be the most salient/sensitive SBRS marker of disease progression. Volumetric MRI showed that increased Lack of Fear was significantly associated with reduced amygdala volume, consistent with our hypothesis that the behavior seen in Sanfilippo syndrome is a variant of Klüver-Bucy syndrome. Hippocampal volume loss had twice the effect on Social-Emotional Dysfunction as amygdala loss, consistent with a hippocampal role in attachment and social emotions. In conclusion, the SBRS assesses the Sanfilippo behavioral phenotype; it can measure behavior change that accompanies disease progression and/or results from treatment.

Trial registration: ClinicalTrials.gov NCT01047306.

Keywords: Behavior phenotype; Behavior rating scale; Sanfilippo Syndrome.

Copyright © 2015 Elsevier Inc. All rights reserved.

Figures

Figure 1. Loess curves for 4 SBRS clusters and 2 domains

Each short vertical line on the abscissa is a single observation (completed form) for a single child. Dashed lines with filled markers indicate clusters/domains that continue to increase across age. Solid lines with empty markers indicate clusters/domains that plateau or decline with increasing age. Markers are placed at 1 year intervals between ages 2 and 8.