Authors :
Presenting Author: Laney Forton, MS – Ambit RD Inc.
Joseph Sullivan, MD – UCSF; Rachel Ritter, MS – Ambit Inc; Jillian McKee, MD, PhD – CHOP; Ingo Helbig, MD – CHOP
Rationale: Angelman Syndrome (AS) and SYNGAP1 are both rare genetic disorders characterized by developmental and neurological problems presenting in the first year of life. Though both disorders are characterized by a number of overlapping symptoms, they present with varying rates of key symptoms which differentiate them. Here, we aim to delineate disease symptoms for patients with SYNGAP1 and AS based on large-scale analysis of healthcare claims data and caregiver-reported survey data to increase the understanding of both disorders as well as differences between how providers and caregivers view impacts on patient care.
Methods: Using published literature and input from expert clinicians, we created a symptom survey for caregivers of individuals diagnosed with SYNGAP1 or AS. The responses were mapped to ICD-10 codes and corresponding human phenotype ontology (HPO) terms and analyzed alongside US claims data (2017 to 2022) to compare frequencies of common key symptoms that differentiate AS and SYNGAP1 and contrast frequencies reported by caregivers versus what physicians code in claims data. Individuals identified in claims for each condition were 21 years old or younger with an ICD-10 code for SYNGAP1 (F78. A1) or AS (Q93.51). Caregiver-reported diagnosis was used for the survey sample. A Fisher exact test was used to determine significance (5%).
Results:
A total of 195 survey respondents reported a genetic diagnosis of SYNGAP1 and 123 a genetic diagnosis of AS. Claims data captured 216 SYNGAP1 and 3,037 AS patients. All 152 symptoms reported in the survey were matched to corresponding ICD-10 and HPO terms. Fourteen of the most relevant symptoms (as determined by a pediatric neurologist with experience managing these disorders) are summarized in Figure 1. As expected, survey frequencies were significantly higher than claims frequencies in both AS and SYNGAP1. Constipation was a symptom that was similar between AS and SYNGAP1 but differed in frequency between claims (38%, 40%) and survey data (80%, 74%). Significantly different symptoms in both data sets between AS and SYNGAP1 include autistic behavior (F84.0), developmental regression (R62.50), and aggressive behavior (F91.8).
Conclusions: Significant differences were identified between AS and SYNGAP1 as well as between survey and claims data frequencies that can be utilized for patient identification. The results illustrate that physicians code relevant terms for treatment and progress, whereas caregivers are more likely to focus on symptoms that correlate with quality of life, therefore highlighting the differences in perceived burden of illness. This difference can make patient identification using claims data exceedingly difficult since many rare conditions have symptomology not readily reported in billing data. Improved reporting of all symptoms can lead to earlier suspicion of these conditions and the potential for earlier diagnosis.
Funding: Ambit funded the data purchase for this abstract.