A rare case of CLN3-associated Iiolated retinal degeneration with macular oedema

Abstract

Introduction: the neuronal ceroid lipofuscinoses (NCLs) comprise a set of hereditary neurodegenerative disorders involving lysosomal storage, and up to this point, they have been linked to 13 genes. Prevalence is one in every 100,000 live births [1]. Historically, the ailment was categorised into various types based on the onset of the disease. Given considerable variations in disease onset and progression, a conclusive diagnosis often necessitates genetic testing and confirmation of the specific sequence variant responsible. As a result, a novel gene-centred nomenclature has been implemented to simplify the classification of the disease. The classic CLN3 disease, characterized by an early onset in adolescence, previously termed "juvenile neuronal ceroid lipofuscinosis" (JNCL) and commonly known as "Batten disease," is a variant of NCL caused by sequence variations in the CLN3 gene (Ceroid Lipofuscinosis, Neuronal, 3; Online Mendelian Inheritance in Man: 204200). This gene is responsible for encoding a transmembrane protein with an unidentified function [2]. The prevalent sequence variant in CLN3 is a homozygous 1 kb deletion, constituting around 85% of JNCL cases [3]. This deletion spans exons 7 to 8, leading to the production of a truncated and non-functional protein. However, other mutations in CLN3 may give rise to an isolated adult-onset retinal degeneration [4]. Confirmation of a JNCL diagnosis may involve the identification of vacuolated lymphocytes and lysosomal (fingerprint) inclusions on a blood film, in addition to molecular genetic testing [2, 5]. Symptoms commonly manifest in early childhood, including vision loss between 4 and 10 years, behavioural and cognitive issues between 7 and 10 years, and progressive motor deterioration and seizures between 10 and 13 years. Ultimately, these complications lead to premature death in the second or third decade of life [6, 7]. This case illustrates that CLN3 mutations can manifest as an isolated retinal phenotype with cystoid macular oedema, and should be considered in atypical cases of this condition.

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ORCID for Andrew John Lotery: orcid.org/0000-0001-5541-4305

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