Moyamoya and homozygous mutation of CLN8 in a Brazilian boy: a previously unreported association

*Correspondence: [e-mail].

Abstract

Case Presentation: A 6-year-old male patient presented with unaltered development until six years of age, when he displayed focal motor and myoclonic seizures, progressing to weekly episodes. Treatment with Valproic acid was introduced and posterior addition of Levetiracetam and Clobazam to control seizures. Concomitantly, neuropsychomotor regression of development, progressive visual impairment and global cerebellar ataxia were also observed. Brain MRI image showed brain and profound cerebellar atrophy, also vascular analysis pointed to a Moyamoya pattern. Electroencephalography showed epileptiform activity in posterior areas, with photoparoxysmal response absent. Bilateral optic atrophy was confirmed by a neuro-ophthalmologist. Based on the clinical evaluation, a gene epilepsy panel revealed the presence of c.792C>G (p.Asn264Lys), a previously described CLN8-pathogenic variant in homozygous fashion.

Discussion: Neuronal ceroid lipofuscinoses (NCL) are a rare and heterogeneous group of neurodegenerative disorders characterized by intracellular accumulation of autofluorescent storage in multiple tissues, especially neurons. At present, thirteen different neuronal ceroid lipofuscinosis (NCL) genes are known. Pathogenic variants in the CLN8 gene cause two distinct allelic diseases, a progressive epilepsy with mental retardation (EPMR) and a more severe variant late infantile with onset around 3–7 years of age and motor decline, severe epilepsy and progressive vision loss, besides ataxia and dystonia. To our knowledge, this is the first reported case of CLN8-related disease in association with Moyamoya, a condition marked by stenosis of distal internal carotid arteries and proximal cerebral arteries causing cerebral ischemia. Moyamoya has been reported in conjunction with a number of diseases (e.g. neurofibromatosis type 1), as well as a handful of lysosomal storage diseases and with CLN6 bi-allelic mutations.

Final Comments: We described a case of Moyamoya in conjunction with homozygous mutations in CLN8. If the association of these two rare conditions reflects a causal relationship, this case raises some important questions about the role and function of CLN8. Additional genetic testing was not done to find any further mutation that could explain the development of Moyamoya.

Publication History

Article published online:
12 May 2025