Development of a Clinical Global Impressions (CGI) Scale for Individuals with Kabuki Syndrome
Clinical Genetics and Therapeutics
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Primary Categories:
- Clinical Genetics
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Secondary Categories:
- Clinical Genetics
Introduction:
Kabuki syndrome (KS) is a Mendelian disorder of the epigenetic machinery with cardinal features including characteristic facies, skeletal anomalies, growth deficiency, and intellectual disability. Individuals with KS also exhibit structural and functional differences such as cleft lip and palate, congenital heart defects, feeding problems, and immunologic issues. Individuals of KS have great variability in which features of the syndrome they manifest. Given the multitude of phenotypes associated with KS, it is difficult to standardize disease severity and outcomes over time. The Clinical Global Impressions (CGI) scale is a systematic tool used in the clinical setting as well as in clinical drug trials to assess disease burden and measure outcomes over time. The establishment of a disease-specific CGI scale for individuals with Kabuki syndrome (CGI-KS) will allow clinicians and researchers to address outcomes that are most important for caregivers of individuals with KS and serve as a potential outcome measure for future clinical trials.
Methods:
To create the domains of the CGI-KS, an interview guide was developed with broad, open-ended questions that allow the caregiver or individual with KS to identify and discuss the symptoms that they view as most impactful to quality of life. Family members of individuals with KS and individuals with KS were recruited from the Kabuki Syndrome Foundation (KSF) and contacted via email to set up a 30–45-minute interview session. Interviews were conducted and recorded on an IRB-approved audio-visual telecommunication application.
Results:
Eleven caregivers of individuals with KS and 2 individuals with KS completed interviews (age range: 2-25 years, mean: 10.8 years). The cohort included 4 males and 7 females with KS with a majority identifying as White. The sample represented many geographic locations with a majority being from the Southeast region of the United States. Preliminary data shows that caregivers and individuals with KS described the following symptoms as most impactful: neurocognitive deficits, hypotonia and coordination difficulties, GI issues (gastroesophageal reflux and feeding difficulties), anxiety, and speech problems.
Conclusion:
Moving forward, additional interviews will be conducted with a goal of completing 30 interviews. All interview data will then be coded to select symptom domains for the CGI-KS. Next, multidisciplinary physicians and scientists with expertise in KS will also be surveyed to create symptom anchors for the rating scales using the domains and symptoms defined by families and individuals with KS. Finally, physicians and providers who are not experts in KS will validate the scale using mock clinical vignettes. Ultimately, development of the CGI-KS will provide a universal measure to accurately track clinical outcomes as well as assess efficacy of potential drug therapy trials in this patient population.
Kabuki syndrome (KS) is a Mendelian disorder of the epigenetic machinery with cardinal features including characteristic facies, skeletal anomalies, growth deficiency, and intellectual disability. Individuals with KS also exhibit structural and functional differences such as cleft lip and palate, congenital heart defects, feeding problems, and immunologic issues. Individuals of KS have great variability in which features of the syndrome they manifest. Given the multitude of phenotypes associated with KS, it is difficult to standardize disease severity and outcomes over time. The Clinical Global Impressions (CGI) scale is a systematic tool used in the clinical setting as well as in clinical drug trials to assess disease burden and measure outcomes over time. The establishment of a disease-specific CGI scale for individuals with Kabuki syndrome (CGI-KS) will allow clinicians and researchers to address outcomes that are most important for caregivers of individuals with KS and serve as a potential outcome measure for future clinical trials.
Methods:
To create the domains of the CGI-KS, an interview guide was developed with broad, open-ended questions that allow the caregiver or individual with KS to identify and discuss the symptoms that they view as most impactful to quality of life. Family members of individuals with KS and individuals with KS were recruited from the Kabuki Syndrome Foundation (KSF) and contacted via email to set up a 30–45-minute interview session. Interviews were conducted and recorded on an IRB-approved audio-visual telecommunication application.
Results:
Eleven caregivers of individuals with KS and 2 individuals with KS completed interviews (age range: 2-25 years, mean: 10.8 years). The cohort included 4 males and 7 females with KS with a majority identifying as White. The sample represented many geographic locations with a majority being from the Southeast region of the United States. Preliminary data shows that caregivers and individuals with KS described the following symptoms as most impactful: neurocognitive deficits, hypotonia and coordination difficulties, GI issues (gastroesophageal reflux and feeding difficulties), anxiety, and speech problems.
Conclusion:
Moving forward, additional interviews will be conducted with a goal of completing 30 interviews. All interview data will then be coded to select symptom domains for the CGI-KS. Next, multidisciplinary physicians and scientists with expertise in KS will also be surveyed to create symptom anchors for the rating scales using the domains and symptoms defined by families and individuals with KS. Finally, physicians and providers who are not experts in KS will validate the scale using mock clinical vignettes. Ultimately, development of the CGI-KS will provide a universal measure to accurately track clinical outcomes as well as assess efficacy of potential drug therapy trials in this patient population.