A New Neurodegenerative Disease of Childhood

Introduction: A new neurodegenerative disease of early childhood was recently identified in seven patients with motor and cognitive regression carrying de novo heterozygous c.628G>A (p.Glu210Lys) UBTF variant. This mutation modifies the initial steps of ribosomal deoxyribonucleic acid transcription necessary for ribosomal biogenesis 1. We found the same mutation by whole exome sequencing in a boy with a similar phenotype in whom all previous etiologic searches were negative.

Case Report: This boy had normal developmental milestones until 2 years old. Then, mild speech and language difficulties and unsteady gait were described. At 5 years old, he had moderate global developmental delay and ataxia. He subsequently presented a slowly progressive behavioral, cognitive, and motor regression with episodes of subacute deterioration, possibly triggered by febrile illnesses. Concurrently, he developed intermittent nonprogressive myoclonus without electroencephalography (EEG) correlate. At 11 years old, he is nonverbal, severely intellectual disabled, and unable to walk alone. Physical examination reveals ataxia and mild dystonic movements. He is normocephalic and no sensory or peripheral nerve impairment was documented.

Brain magnetic resonance imagings showed progressive corticosubcortical atrophy and diffuse T2 white matter hyperintensities but preserved cerebellum. EEGs revealed generalized spike waves with normal background activity; pseudoperiodic delta waves were observed intermittently between 7 and 9 years old. Extensive workup for metabolic, infectious, and inflammatory disorders, CGH array, and genetic panel was negative.

Conclusion: This case is, to our knowledge, the first reported since Edvardson et al's¹ publication in August 2017. It supports the phenotype–genotype correlation and brings new insights into the clinical features of this disease that unveils new mechanisms of neurodegeneration.

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