Brain Magnetic Resonance Imaging (MRI) Pattern Recognition in Pol III-Related Leukodystrophies

Abstract

Pol III-related leukodystrophies are caused by mutations in POLR3A and POLR3B genes and all share peculiar imaging and clinical features. The objectives of this study are (1) to define the neuroradiologic pattern in a cohort of POLR3A and POLR3B subjects and (2) to compare the neuroradiologic pattern of Pol III-related leukodystrophies with other hypomyelinating disorders. The magnetic resonance imaging (MRI) examinations of 13 patients with POLR3A and POLR3B mutations and of 14 patients with other hypomyelinating disorders were analyzed. All the subjects with Pol III-related leukodystrophies presented hypomyelination associated with T2 hypointensity of the thalami and/or the pallida. Twelve subjects (92%) presented T2 hypointensity of the optic radiations. Cerebellar atrophy was observed in most patients (92%). The combination of the analyzed criteria identified patients with Pol III-related leukodystrophies with a sensitivity of 84.6% and a specificity of 92.9%.

Keywords

leukodystrophy magnetic resonance imaging hypomyelination

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References

van der Knaap

Breiter

Naidu

. Defining and categorizing leukoencephalopathies of unknown origin: MR imaging approach. Radiology. 1999;213:121–133.

Schiffmann

van der Knaap

. The latest on leukodystrophies. Curr Opin Neurol. 2004;17:187–192.

Steenweg

Vanderver

Blaser

. Magnetic resonance imaging pattern recognition in hypomyelinating disorders. Brain. 2010;133:2971–2982.

Wolf

Harting

Boltshauser

. Leukoencephalopathy with ataxia, hypodontia, and hypomyelination. Neurology. 2005;64:1461–1464.

Wolf

Harting

Innes

. Ataxia, delayed dentition and hypomyelination: a novel leukoencephalopathy. Neuropediatrics. 2007;38:64–70.

Bernard

Vanderver

. Pol III-related leukodystrophies. In: Pagon

Bird

Dolan

, et al, eds. GeneReviews™ [Internet]. Seattle, WA: University of Washington, Seattle; 1993. Available at: http://www.ncbi.nlm.nih.gov/books/NBK99167/, accessed August 2, 2012.

Atrouni

Daraze

Tamraz

. Leukodystrophy associated with oligodontia in a large inbred family: fortuitous association or new entity? Am J Med Genet A. 2003;118A:76–81.

Timmons

Tsokos

Asab

. Peripheral and central hypomyelination with hypogonadotropic hypogonadism and hypodontia. Neurology. 2006;67:2066–2069.

Bekiesinska-Figatowska

Mierzewska

Kuczynska-Zardzewialy

. Hypomyelination, hypogonadotropic hypogonadism, hypodontia—first Polish patient. Brain Dev. 2010;32:574–578.

10.

Orcesi

Tonduti

Uggetti

. New case of 4H syndrome and a review of the literature. Pediatr Neurol. 2010;42:359–364.

11.

Vázquez-López

Ruiz-Martín

de Castro-De Castro

. Central hypomyelination, hypogonadotrophic hypogonadism and hypodontia: a new leukodystrophy. Rev Neurol. 2008;47:204-208.

12.

Chouery

Delague

Jalkh

. A whole-genome scan in a large family with leukodystrophy and oligodontia reveals linkage to 10q22. Neurogenetics. 2011;12:73–78.

13.

Bernard

Thiffault

Tetreault

. Tremor–ataxia with central hypomyelination (TACH) leukodystrophy maps to chromosome 10q22.3–10q23.31. Neurogenetics. 2010;11:457–464.

14.

Bernard

Chouery

Putorti Maria

. Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause a recessive hypomyelinating leukodystrophy. Am J Hum Genet. 2011;89:415–423.

15.

Saitsu

Osaka

Sasaki

. Mutations in POLR3A and POLR3B encoding RNA polymerase III subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy. Am J Hum Genet. 2011;89:644–651.

16.

Tétreault

Choquet

Orcesi

. Recessive mutations in POLR3B, encoding the second largest subunit of Pol III, cause a rare hypomyelinating leukodystrophy. Am J Hum Genet. 2011;89:652–655.

17.

Sasaki

Takanashi J-i, Tada H . Diffuse cerebral hypomyelination with cerebellar atrophy and hypoplasia of the corpus callosum. Brain Dev. 2009;31:582–587.

18.

Schenker

Meier

Wichmann

. Age distribution and iron dependency of the T2 relaxation time in the globus pallidus and putamen. Neuroradiology. 1993;35:119–124.

19.

Landis

Koch

. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159–174.

20.

Takanashi

Osaka

Saitsu

. Different patterns of cerebellar abnormality and hypomyelination between POLR3A and POLR3B mutations. Brain Dev. 2013.

21.

Poretti

Wolf

Boltshauser

. Differential diagnosis of cerebellar atrophy in childhood. Eur J Paediatr Neurol. 2008;12:155–167.

22.

Sonninen

Autti

Varho

. Brain involvement in Salla disease. AJNR Am J Neuroradiol. 1999;20:433–443.

23.

Koob

Laugel

Durand

. Neuroimaging in cockayne syndrome. Am J Neuroradiol. 2010;31:1623–1630.

24.

Galluzzi

Rufa

Balestri

. MR brain imaging of fucosidosis type I. Am J Neuroradiol. 2001;22:777–780.

25.

Loddenkemper

Grote

Evers

. Neurological manifestations of the oculodentodigital dysplasia syndrome. J Neurol. 2002;249:584–595.

26.

Moons

Grobbee

. When should we remain blind and when should our eyes remain open in diagnostic studies? J Clin Epidemiol. 2002;55:633–636.