Susceptibility-Weighted Imaging for Calcification in Cockayne Syndrome
A
9-year-old girl with microcephaly, failure to thrive, progressive visual and hearing loss, facial dysmorphic features, and increasing headaches and vomiting underwent brain magnetic resonance imaging (MRI). T2weighted images demonstrated nonspecific reduction in size and diffuse hyperintense signal of the supratentorial white matter with hypointense foci representing preserved perivascular myelin (Figure, A). Additionally, cerebral and cerebellar atrophy was noted (Figure, C and D). Susceptibility-weighted imaging (SWI) showed symmetric, hypointense, punctate foci in the globi pallidi consistent with calcifications (Figure, B). Clinical and neuroimaging findings were suggestive of Cockayne syndrome (CS),
Mendelian Inheritance in Man (OMIM) 216400. Genetic analysis revealed a homozygous nonsense mutation in ERCC8, which is predicted to cause premature protein termination and confirms the diagnosis of CS. CS is a rare autosomal recessive, multisystem disorder that belongs to the family of damaged DNA repair disorders.1 Clinical features include cachectic dwarfism, neurodevelopmental delay, cutaneous photosensitivity, progressive pigmentary retinopathy, neurosensory hearing loss, dental caries, and characteristic physical features.1 Neuroimaging findings in CS that may suggest the diagnosis include abnormal signal of the white matter, progressive atrophy of cerebellum and/or cerebrum, and calcifications.2 Calcifications are typically bilateral and symmetric, range from punctuate to severe, and are usually located in the basal ganglia, dentate nuclei, cortex, and, more rarely, white matter and thalami.2 SWI is a gradient-echo MRI sequence with a high sensitivity for blood, blood products, nonheme iron, and calcifications within the brain.3 SWI may detect calcifications with higher sensitivity compared with other MRI sequences, potentially leading to earlier diagnosis of CS. SWI can obviate the need for head computed tomography to check for calcifications. In children with suspicion of neurodegenerative disorders, metabolic diseases, or other long-standing processes, SWI should be considered a part of the MRI protocol to search for calcifications.3 n Matthias W. Wagner, MD Andrea Poretti, MD Section of Pediatric Neuroradiology Division of Pediatric Radiology Russell H. Morgan Department of Radiology and Radiological Science
Tao Wang, MD, PhD McKusick–Nathans Institute of Genetic Medicine Department of Pediatrics
Thomas O. Crawford, MD Figure. A, Axial T2-weighted image shows reduction in size and diffuse hyperintense signal of the supratentorial white matter with hypointense foci representing preserved perivascular myelin. B, Axial SWI image demonstrates hypointense punctuate foci in the globi pallidi consistent with calcifications (arrows). C, Sagittal T1-weighted image at 2 years of age reveals normal size of the cerebellum. D, Sagittal T1-weighted image at 9 years of age shows cerebellar atrophy.
Department of Neurology
Thierry A.G.M. Huisman, MD Thangamadhan Bosemani, MD Section of Pediatric Neuroradiology Division of Pediatric Radiology Russell H. Morgan Department of Radiology and Radiological Science The Johns Hopkins University School of Medicine Baltimore, Maryland
References available at www.jpeds.com J Pediatr 2014;-:---. 0022-3476/$ - see front matter. Copyright ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2014.04.030
1
THE JOURNAL OF PEDIATRICS
www.jpeds.com
References 1. Laugel V. Cockayne syndrome: the expanding clinical and mutational spectrum. Mech Ageing Dev 2013;134:161-70.
1.e1
Vol. -, No. 2. Koob M, Laugel V, Durand M, et al. Neuroimaging in Cockayne syndrome. Am J Neuroradiol 2010;31:1623-30. 3. Bosemani T, Poretti A, Huisman TA. Susceptibility-weighted imaging in pediatric neuroimaging. J Magn Reson Imaging 2013. epub Nov 4.
Wagner et al
A
9-year-old girl with microcephaly, failure to thrive, progressive visual and hearing loss, facial dysmorphic features, and increasing headaches and vomiting underwent brain magnetic resonance imaging (MRI). T2weighted images demonstrated nonspecific reduction in size and diffuse hyperintense signal of the supratentorial white matter with hypointense foci representing preserved perivascular myelin (Figure, A). Additionally, cerebral and cerebellar atrophy was noted (Figure, C and D). Susceptibility-weighted imaging (SWI) showed symmetric, hypointense, punctate foci in the globi pallidi consistent with calcifications (Figure, B). Clinical and neuroimaging findings were suggestive of Cockayne syndrome (CS),
Mendelian Inheritance in Man (OMIM) 216400. Genetic analysis revealed a homozygous nonsense mutation in ERCC8, which is predicted to cause premature protein termination and confirms the diagnosis of CS. CS is a rare autosomal recessive, multisystem disorder that belongs to the family of damaged DNA repair disorders.1 Clinical features include cachectic dwarfism, neurodevelopmental delay, cutaneous photosensitivity, progressive pigmentary retinopathy, neurosensory hearing loss, dental caries, and characteristic physical features.1 Neuroimaging findings in CS that may suggest the diagnosis include abnormal signal of the white matter, progressive atrophy of cerebellum and/or cerebrum, and calcifications.2 Calcifications are typically bilateral and symmetric, range from punctuate to severe, and are usually located in the basal ganglia, dentate nuclei, cortex, and, more rarely, white matter and thalami.2 SWI is a gradient-echo MRI sequence with a high sensitivity for blood, blood products, nonheme iron, and calcifications within the brain.3 SWI may detect calcifications with higher sensitivity compared with other MRI sequences, potentially leading to earlier diagnosis of CS. SWI can obviate the need for head computed tomography to check for calcifications. In children with suspicion of neurodegenerative disorders, metabolic diseases, or other long-standing processes, SWI should be considered a part of the MRI protocol to search for calcifications.3 n Matthias W. Wagner, MD Andrea Poretti, MD Section of Pediatric Neuroradiology Division of Pediatric Radiology Russell H. Morgan Department of Radiology and Radiological Science
Tao Wang, MD, PhD McKusick–Nathans Institute of Genetic Medicine Department of Pediatrics
Thomas O. Crawford, MD Figure. A, Axial T2-weighted image shows reduction in size and diffuse hyperintense signal of the supratentorial white matter with hypointense foci representing preserved perivascular myelin. B, Axial SWI image demonstrates hypointense punctuate foci in the globi pallidi consistent with calcifications (arrows). C, Sagittal T1-weighted image at 2 years of age reveals normal size of the cerebellum. D, Sagittal T1-weighted image at 9 years of age shows cerebellar atrophy.
Department of Neurology
Thierry A.G.M. Huisman, MD Thangamadhan Bosemani, MD Section of Pediatric Neuroradiology Division of Pediatric Radiology Russell H. Morgan Department of Radiology and Radiological Science The Johns Hopkins University School of Medicine Baltimore, Maryland
References available at www.jpeds.com J Pediatr 2014;-:---. 0022-3476/$ - see front matter. Copyright ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2014.04.030
1
THE JOURNAL OF PEDIATRICS
www.jpeds.com
References 1. Laugel V. Cockayne syndrome: the expanding clinical and mutational spectrum. Mech Ageing Dev 2013;134:161-70.
1.e1
Vol. -, No. 2. Koob M, Laugel V, Durand M, et al. Neuroimaging in Cockayne syndrome. Am J Neuroradiol 2010;31:1623-30. 3. Bosemani T, Poretti A, Huisman TA. Susceptibility-weighted imaging in pediatric neuroimaging. J Magn Reson Imaging 2013. epub Nov 4.
Wagner et al
