Neuropediatrics 2018; 49(02): 112-117
DOI: 10.1055/s-0037-1608780
Original Article
Georg Thieme Verlag KG Stuttgart · New York

4H Leukodystrophy: Lessons from 3T Imaging

Ferdy K. Cayami
1   Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands
2   Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
3   Center for Biomedical Research, Faculty of Medicine Diponegoro University, Semarang, Indonesia
,
Marianna Bugiani
2   Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
4   Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
5   Amsterdam Neuroscience, Amsterdam, The Netherlands
,
Petra J.W. Pouwels
5   Amsterdam Neuroscience, Amsterdam, The Netherlands
6   Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands
,
Geneviève Bernard
7   Department of Neurology and Neurosurgery, McGill University, Montreal, Canada
8   Department of Pediatrics, McGill University, Montreal, Canada
9   Department of Medical Genetics, Montreal Children's Hospital, McGill University Health Center, Montreal, Canada
10   Child Health and Human Development Program, Research Institute of the McGill University Health Center, Montreal, Canada
,
Marjo S. van der Knaap
2   Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
5   Amsterdam Neuroscience, Amsterdam, The Netherlands
11   Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University and VU Medical Center, Amsterdam, The Netherlands
,
Nicole I. Wolf
2   Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
5   Amsterdam Neuroscience, Amsterdam, The Netherlands
› Author Affiliations
Further Information

Publication History

25 September 2017

04 October 2017

Publication Date:
27 November 2017 (online)

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Abstract

4H leukodystrophy is characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. With its variability in clinical symptoms, application of pattern recognition to identify specific magnetic resonance imaging (MRI) features proved useful for the diagnosis. We collected 3T MR imaging data of 12 patients with mutations in POLR3A (n = 8), POLR3B (n = 3), and POLR1C (n = 1), all obtained at the same scanner. We assessed these images and compared them with previously obtained 1.5T images in 8 patients. Novel MRI findings were myelin islets, closed eye sign, and a cyst-like lesion in the splenium. Myelin islets were variable numbers of small T1 hyperintense and T2 hypointense dots, mostly in the frontal and parietal white matter, and present in all patients. This interpretation was supported with perivascular staining of myelin protein in the hypomyelinated white matter of a deceased 4H patient. All patients had better myelination of the medial lemniscus with a relatively hypointense signal of this structure on axial T2-weighted (T2W) images (“closed eye sign”). Five patients had a small cyst-like lesion in the splenium. In 10 patients with sagittal T2W images, we also found spinal cord hypomyelination. In conclusion, imaging at 3T identified additional features in 4H leukodystrophy, aiding the MRI diagnosis of this entity.