Dados do Trabalho
MOYAMOYA AND HOMOZYGOUS MUTATION OF CLN8 IN A BRAZILIAN BOY – A PREVIOUSLY UNREPORTED ASSOCIATION
Apresentação do caso
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 posteri 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.
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.
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.
Referências (se houver)
Neuronal ceroid lipofuscinosis, CLN8, Moyamoya
Fonte de Fomento (se houver)
Declaração de conflito de interesses de TODOS os autores
The authors have no conflicts of interest.
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP - São Paulo - Brasil
Ana Beatriz Arruda Carvalho de Oliveira, Joemir Jábson da Conceição Brito, Flora Cruz de Almeida Ximenes, Renata Silva de Mendonça, Andreia Braga Mota Azzoni, Mariana Piva da Costa, Daniel Shoij Hayashi, Pedro Carrijo Costa, Clarissa Bueno