Exploring Simplified Screening Cut-Offs: Classification of KCNQ2-DEE Patients into Age-Adjusted Disease Phenotypes


Gold A1, Suminski N1, Doma R1, Rudell K2, L'Italien G3, Potashman M3
1Parexel International LLC, Durham, NC, USA, 2Parexel International, LONDON, LON, UK, 3Biohaven Pharmaceuticals, New Haven, CT, USA

OBJECTIVES: KCNQ2 Developmental and Epileptic Encephalopathy (KCNQ2-DEE) is a rare, early onset condition that involves seizures in infancy and a range of developmental impairments throughout life. The heterogeneity of signs, symptoms, and impacts across age groups makes assigning severity based on phenotypic presentation challenging. Cossu et al. (2023) defined three phenotypic categories (mild, severe, and profound), based on neurodevelopmental features and symptoms. This criterion was developed to derive phenotype classifications in a KCNQ2-DEE interview study.

METHODS: 53 parents of children with KCQN2-DEE, 1-18 years of age, were recruited for a concept elicitation study. The preliminary screening interview included questions about gross motor function (e.g., walking) and communication abilities (e.g., speaking) to categorize the children as either mild, severe, or profound. Children were further categorized by age (in years) into five groups (1-2, 3-5, 6-8, 9-11, 12-18). Participants were classified by phenotypic severity and age so that a representative sample could be recruited. KCNQ2-DEE expert input (n=3) was obtained mid-study to review the domains and abilities by age, and the phenotypic classifications were updated to help better reflect all age ranges.

RESULTS: We identified that the criteria and the neurodevelopmental variance due to age led to the potential for misclassification. Using only gross motor and communication as a classification of severity in the youngest age groups (1-2; 3-5) resulted in skewed effects, as it led to children being overcategorized into the profound phenotype group. Phenotypic categorization was updated, with consideration to Cossu et al, to include feeding ability (self-fed, assisted, or tube feeding), resulting in the re-classification of n=8 participants.

CONCLUSIONS: Re-classifying participants in consideration of their age and feeding criteria increased data quality, and representativeness of the study sample recruited. For highly heterogenous populations, appropriate classifications based on age and severity is critical.

Conference/Value in Health Info

2024-05, ISPOR 2024, Atlanta, GA, USA

Value in Health, Volume 27, Issue 6, S1 (June 2024)




Clinical Outcomes, Organizational Practices

Topic Subcategory

Best Research Practices, Clinical Outcomes Assessment


Neurological Disorders, Pediatrics

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