Childhood neurodegeneration associated with a specific UBTF variant: a new case report and review of the literature

• Published in: BMC neurology Vol. 20; no. 1; p. 17
• Main Authors: Bastos, Filipa, Quinodoz, Mathieu, Addor, Marie-Claude, Royer-Bertrand, Beryl, Fodstad, Heidi, Rivolta, Carlo, Poloni, Claudia, Superti-Furga, Andrea, Roulet-Perez, Eliane, Lebon, Sebastien
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 13-01-2020; BioMed Central; BMC
• Subjects: Age; Ataxia; Atrophy; Biosynthesis; Case Report; Case reports; Child; Childhood; Children; Cognitive ability; Diagnosis; Disease; Diseases; EEG; Electroencephalography; Family medical history; Genetic aspects; Genetic Variation; Genotype; Genotype & phenotype; Genotypes; Health aspects; Humans; Intellectual disabilities; Literature reviews; Magnetic resonance imaging; Male; Metabolism; Nervous system; Nervous system diseases; Neurodegeneration; Neurodegenerative diseases; Neurodegenerative Diseases - genetics; Patients; Pediatric neurology; Phenotype; Phenotypes; Pol1 Transcription Initiation Complex Proteins - genetics; Proteins; Ribosomal DNA; RNA polymerase; Sleep; Transcription factors; UBTF; Switzerland; UBTF; Neurodegeneration; EEG
• ISSN: 1471-2377; 1471-2377
• DOI: 10.1186/s12883-019-1586-x

A new monogenic neurodegenerative disease affecting ribosomal metabolism has recently been identified in association with a monoallelic UBTF putative gain of function variant (NM_001076683.1:c.628G>A, hg19). Phenotype is consistent among these probands with progressive motor, cognitive, and behavioural regression in early to middle childhood.
We report on a child with this monoallelic UBTF variant who presented with progressive disease including regression, episodes of subacute deterioration during febrile illnesses and a remarkable EEG pattern with a transient pattern of semi-periodic slow waves.
This case further supports the phenotype-genotype correlation of neurodegeneration associated with UBTF c.628G>A. Moreover, it brings new insights into the clinical features and EEG that could possibly serve as diagnostic markers of this otherwise nonspecific phenotype.