Clinical Symptoms in Late Infantile and Juvenile Onset Neuronal Ceroid Lipofuscinosis Type 7 (CLN7 Disease).

BACKGROUND

Neuronal ceroid lipofuscinosis type 7 (CLN7 disease) can present with late-infantile or juvenile onset phenotypes. Current understanding of disease progression is limited as most published data derive from case reports or case series. Our goal was to characterize clinical aspects of CLN7 disease across phenotypes.

METHODS

Participants with CLN7 disease were enrolled in a longitudinal observational study. We obtained medical and developmental histories, assessed adaptive behavior ability, and conducted standardized NCL-specific assessments, including the Unified Batten Disease Rating Scale and/or the Hamburg late infantile NCL rating scale.

RESULTS

We enrolled 5 participants with late infantile onset and 2 participants with juvenile onset CLN7 disease. Those with late-infantile CLN7 disease typically demonstrated normal early development followed by a plateau in language development. Initial symptoms were commonly cognitive/learning problems (median onset 3.0 years). Developmental regression started between ages 4 and 6 years, with loss of independent ambulation and expressive language by age 6 years. In contrast, both participants with juvenile onset CLN7 disease had normal early development with vision loss as the initial symptom (ages 10-12.5 years), followed by seizure onset within 4 years.

CONCLUSIONS

Late-infantile and juvenile onset phenotypes of CLN7 disease have distinct natural histories and progression patterns, including typical presenting symptoms, presence of developmental regression and differences in disease course. Disease progression in the juvenile cohort was more protracted compared to the late infantile cohort. Characterizing the natural history of CLN7 disease phenotypes is essential for improving early diagnosis, improving clinical management, and supporting therapeutic development for this devastating disorder.