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      NEUROIMAGE Year : 2023  |  Volume : 71  |  Issue : 5  |  Page : 1098-1099

Neuroimaging of POLR3B-related Hypomyelinating Leukodystrophy

Luiz F M Borella1, Danilo A Pereira2, Fabiano Reis1
1 Department of Radiology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil
2 Department of Human Reproduction and Childhood, Pontifical Catholic University of São Paulo (PUC-SP), Sorocaba, SP, Brazil

Date of Submission04-Jul-2023Date of Decision08-Jul-2023Date of Acceptance08-Jul-2023Date of Web Publication18-Oct-2023

Correspondence Address:
Luiz F M Borella
Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, 13083-887 Campinas SP
Brazil

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/0028-3886.388056

How to cite this article:
M Borella LF, Pereira DA, Reis F. Neuroimaging of POLR3B-related Hypomyelinating Leukodystrophy. Neurol India 2023;71:1098-9

A 15-year-old female patient presented with ataxia, intellectual disability, abnormal dentition, growth hormone deficiency, short stature, delayed puberty, and myopia, first noticed at the age of 9 years. Magnetic resonance imaging (MRI) showed suggestive features of hypomyelinating leukodystrophy [Figure 1]. 4H leukodystrophy (4H) (OMIM 614381) was diagnosed by genetic analysis, which demonstrated pathogenic heterozygous variants of the POLR3B gene as the following: Chr12:106.433.780 A>C (or alternatively c.1689A>C - ENST00000228347); Chr12:106.433.814T>C (or alternatively c.1723T>C - ENST00000228347) and Chr12:106.432.421 T>A (or alternatively c.1568T>A - ENST00000228347).

Figure 1: T1-weighted images (T1WI) and T2-weighted images (T2WI) of brain MRI showing diffuse T2 hyperintense signal of cerebral white matter (black arrows in a), with relative preservation of perirolandic cortex (black arrows in b), T2 hypointensity of the optic radiation (black arrows in c), and the anterolateral thalamus (black arrows in d), and corpus callosum and cerebellar atrophy (white arrows in e and black arrows in f)

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A group of four clinically overlapping hypomyelinating leukodystrophies has been described with mutations in polymerase 3 enzyme (Pol 3) subunits.[1] Mutations in POLR3A and POLR3B genes may appear at any given coding exon or splicing junctions of these genes, which shows the high degree of mutational heterogeneity of Pol 3-associated leukodystrophies.

Clinically, the patients affected by Pol 3-related leukodystrophies manifest between early childhood to adolescence, usually demonstrating motor delay or regression, with upper motor neuron signs, cerebellar dysfunctions, and some milder degree of cognitive impairment. Dental abnormalities and hypogonadotropic hypogonadism are commonly observed.[2]

The MRI patterns indicate hypomyelination (a necessary MRI criterion), which refers to a permanent, substantial deficit in myelin deposition in the brain.[3],[4] Other features include diffuse atrophy of the cerebellum and a thin corpus callosum.

Considering this case, and all reported in the literature (less than 50 until the present), these data suggest that this observed pattern of leukodystrophy should be searched on MRI, and if present, genetic analysis should be performed.

Declaration of patient consent

Full and detailed consent from the patient/guardian has been taken. The patient's identity has been adequately anonymized. If anything related to the patient's identity is shown, adequate consent has been taken from the patient/relative/guardian. The journal will not be responsible for any medico-legal issues arising out of issues related to the patient's identity or any other issues arising from the public display of the images.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 

  References 
1.Daoud H, Tétreault M, Gibson W, Guerrero K, Cohen A, Gburek-Augustat J, et al. Mutations in POLR3A and POLR3B are a major cause of hypomyelinating leukodystrophies with or without dental abnormalities and/or hypogonadotropic hypogonadism. J Med Genet 2013;50:194-7.  
    2.Bernard G, Chouery E, Putorti ML, Tétreault M, Takanohashi A, Carosso G, et al. Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause a recessive hypomyelinating leukodystrophy. Am J Hum Genet 2011;89:415-23.  
    3.Steenweg ME, Vanderver A, Blaser S, Bizzi A, de Koning TJ, Mancini GM, et al. Magnetic resonance imaging pattern recognition in hypomyelinating disorders. Brain 2010;133:2971-82.  
    4.Schiffmann R, van der Knaap MS. Invited article: An MRI-based approach to the diagnosis of white matter disorders. Neurology 2009;72:750-9.  
    
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