Oral Presentation International Congress on Neuronal Ceroid Lipofuscinoses 2025

Clinical Symptoms in Late Infantile and Juvenile Onset CLN7 Disease (124448)

Jennifer Vermilion 1 , Marianna Pereira Freitas 1 , Amy Vierhile 1 , Heather R. Adams 1 , Erika F. Augustine 2 , Jonathan W. Mink 3
  1. University of Rochester Batten Center, Rochester, NY, United States
  2. Kennedy Krieger Institute, Baltimore, MD, USA
  3. Consultant , Pittsford, New York, United States

Introduction:  CLN7 disease can present as late infantile or juvenile neuronal ceroid lipofuscinosis (LINCL, JNCL); due to its ultra-rare prevalence, data on the natural history for both disease presentations is sparse.  Understanding the clinical course of LINCL and JNCL CLN7 diseases is critical to improving the ability to design clinical trials.

Methods: We collected data from two natural history studies at the University of Rochester Batten Center. Participants completed the Unified Batten Disease Rating Scale (UDBRS), a global NCL severity rating scale. In one study, medical and developmental histories were obtained through a semi-structured interview.

Results: We enrolled 4 participants with late infantile (LINCL) onset and 4 participants with juvenile (JNCL) onset across both studies. In the LINCL cohort, median age (range) at baseline assessment was 6.4 (5.7-8.4) years. All participants achieved early gross motor and fine motor milestones on time. Only 1 participant ever spoke in complete sentences. All participants experienced regression in language and motor function. NCL symptoms started with cognitive concerns (median 3.3 years, range 2.2-4.6), followed by motor concerns (median 3.5 years, range 2.3-4.1), seizure onset (median 4.0 years, range 4.0-4.2) and vision loss (median 5.5 years, range 2.3-5.6). In the JNCL cohort, median age (range) at baseline assessment was 18.1 (range 6.1-28.7) years. For the 2 participants with developmental history data, both achieved early developmental milestones on time. NCL symptom onset was available for all 4 JNCL participants. All participants reported vision loss (median 11.1 years, range 5.1-12.5) and seizures (median 13.9 years, range 6.1-15.8). Motor problems and cognitive problems were only reported in 2 participants. 

Conclusions: The LINCL and JNCL onsets of CLN7 disease differ by impact on early development and developmental regression, symptom manifestation and order of symptoms onset. These data are valuable for understanding the natural histories of these diseases.