Abstracts

Rationale: Neuronal Ceroid Lipofuscinosis type 2 (CLN2) disease is a rare, neurodegenerative lysosomal storage disorder characterized by language delay, epilepsy, progressive motor and cognitive decline, blindness, and premature death as early as the first decade of life. Although there is often a history of language delay, additional clinical work-up may not be prompted until new onset of seizures, commonly presenting between 2-4 years of age. Average age of diagnosis is 4.9 years (DEM-CHILD database), which is ~2 years after seizure onset, during which significant neurodegeneration has occurred. Timely and appropriate use of genetic testing may shorten the diagnostic journey, avoid unnecessary and potentially invasive medical procedures or evaluations, and impact clinical management. The objective of this report is to show how genetic testing can shorten time to an accurate diagnosis of CLN2 disease which presents with predictable, yet non-specific, clinical signs and symptoms.  Methods: Behind the Seizure™ (BTS; initiated January 2017) is a no-cost epilepsy gene panel testing program for children <5 years of age who experience an unprovoked seizure. Ordering physicians indicated if the patient had the following signs/symptoms: language delay, motor difficulty (ataxia, clumsiness, and/or frequent falls), abnormal EEG, abnormal brain MRI, language development delay preceding seizure onset, and/or developmental delay preceding seizure onset. Follow-up interviews were conducted to ascertain in greater granularity the patients' clinical presentations prior to diagnosis through BTS.  Results: As of February 25th, 2019, 6 patients with CLN2 disease were diagnosed through BTS (n=682 screened). The ordering physicians were 4 pediatric neurologists and 2 geneticists. Follow-up interviews were conducted with the ordering physician, other healthcare team members, and/or parents.Average age of diagnosis was 3.9 years. First referred symptom of all patients prior to diagnosis was seizures, with an average age of onset of 2.8 years. Average time between first seizure and diagnosis was 13 months. After further evaluation of the clinical presentations prior to diagnosis, all patients were noted to have language delay prior to seizure onset. Four patients had a delay in developing a two-word sentence (occurring >24 months or never able to develop ability), and all patients had a delay in developing a whole sentence (occurring >36 months or never able to develop ability). Prior to diagnosis, in four patients, ataxia occurred after language delay and seizures and no significant vision changes were noted.  Conclusions: These results show the impact of genetic testing on diagnosing patients with CLN2 disease at an earlier age (BTS: 3.9 years of age vs. 4.9 previously reported). Genetic testing should be considered in children with early-onset language delay and unprovoked seizures. Larger prospective studies are encouraged to verify findings.  Funding: No funding