OBJECTIVES: The HS-FOCUS questionnaire was used to monitor patient reported outcomes for mucopolysaccharidosis II (MPS II, Hunter Syndrome) patients. Preliminary item analysis    suggested that some of the items were redundant and/or not informative. The objective of this study was to shorten HS-FOCUS without compromising the psychometric properties of the original patient and parent versions while reducing the respondent’s burden. METHODS: Data collected in a randomized trial were used. Final items were selected based on  their content validity, per clinicians’ input and by item performance as described below. Reliability, validity, and ability to detect change were assessed in the shortened version of the HS-FOCUS.  RESULTS:   Forty-nine patients above 12 years old and 84 parents completed the HS-FOCUS. Items were removed owing to ambiguous wordings, floor effects (>60%), high inter-item correlations (>0.90) and inadequate content or clinical relevance. The Sleeping domain was removed from both the shortened patient (32 items) and parent versions (35 items), which kept 5 functional domains. The internal consistency and test-retest reliability were >0.70 for all domains except the Breathing domain in patients. The test-retest reliability was assessed using responses at Baseline and Week 18 and was > 0.70 for all domains except the Schooling/Work for parents’ version. Significant correlation (>0.30) with similar concepts of other instruments and the 6-Minute-Walk test demonstrated concurrent validity. Scores were significantly different in all domains among levels of disability as measured by CHAQ disability score (CHAQ-DIS). Changes in domain scores were responsive to changes in patients’ health status also measured by the CHAQ-DIS. CONCLUSIONS: The shortened HS-FOCUS will reduce patient and parent burden without compromising its measurement properties. The shortened HS-FOCUS is a reliable and valid instrument for use in clinical trials or registries, with increased ability to detect change compared to the original version.