Static Leukoencephalopathy Associated with 17p13.3 Microdeletion Syndrome: A Case Report

Abstract

Background Leukoencephalopathy associated with dysmorphic features may be attributed to chromosomal abnormalities such as 17p13.3 microdeletion syndrome.

Case A 19-year-old female patient was referred to our hospital for diagnostic evaluation of her leukoencephalopathy. She demonstrated moderate intellectual disability, minor dysmorphic features, and short stature. Serial brain magnetic resonance images obtained within a 16-year interval revealed prolonged T2 signals in the deep cerebral white matter with enlarged Virchow–Robin spaces. A nonsymptomatic atlas anomaly was also noted. Using microarray-based comparative genomic hybridization, we identified a 2.2-Mb terminal deletion at 17p13.3, encompassing YWHAE, CRK, and RTN4RL1 but not PAFAH1B1.

Conclusion Except for atlas anomaly, the patient's clinical and imaging findings were compatible with the diagnosis of 17p13.3 microdeletion syndrome. The white matter abnormality was static and nonprogressive. The association between the atlas abnormality and this deletion remains elusive. We note the importance of exploring submicroscopic chromosomal imbalance when patients show prominent but static white matter abnormalities with discrepantly mild and stable neurological signs.

Keywords

17p13.3 microdeletion - YWHAE - PAFAH1B1 - leukoencephalopathy - Virchow–Robin space

Ethics

This study was approved by the Institutional Review Board of the National Center of Neurology and Psychiatry. The parents of the patient provided written informed consent. Written informed consent was obtained from both the patient and her mother for the publication of the patient's images.

• References

• 1 Schiff M, Delahaye A, Andrieux J. , et al. Further delineation of the 17p13.3 microdeletion involving YWHAE but distal to PAFAH1B1: four additional patients. Eur J Med Genet 2010; 53 (05) 303-308
• 2 Emrick LT, Rosenfeld JA, Lalani SR. , et al. Microdeletions excluding YWHAE and PAFAH1B1 cause a unique leukoencephalopathy: further delineation of the 17p13.3 microdeletion spectrum. Genet Med 2019; 21: 1652-1656
• 3 Barros Fontes MI, Dos Santos AP, Rossi Torres F. , et al. 17p13.3 microdeletion: insights on genotype-phenotype correlation. Mol Syndromol 2017; 8 (01) 36-41
• 4 Nagamani SC, Zhang F, Shchelochkov OA. , et al. Microdeletions including YWHAE in the Miller-Dieker syndrome region on chromosome 17p13.3 result in facial dysmorphisms, growth restriction, and cognitive impairment. J Med Genet 2009; 46 (12) 825-833
• 5 Bruno DL, Anderlid BM, Lindstrand A. , et al. Further molecular and clinical delineation of co-locating 17p13.3 microdeletions and microduplications that show distinctive phenotypes. J Med Genet 2010; 47 (05) 299-311
• 6 Toyo-oka K, Shionoya A, Gambello MJ. , et al. 14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome. Nat Genet 2003; 34 (03) 274-285
• 7 Park TJ, Curran T. Crk and Crk-like play essential overlapping roles downstream of disabled-1 in the Reelin pathway. J Neurosci 2008; 28 (50) 13551-13562
• 8 Østergaard JR, Graakjær J, Brandt C, Birkebæk NH. Further delineation of 17p13.3 microdeletion involving CRK. The effect of growth hormone treatment. Eur J Med Genet 2012; 55 (01) 22-26
• 9 Fournier AE, GrandPre T, Strittmatter SM. Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature 2001; 409 (6818): 341-346
• 10 Urasaki E, Yasukouchi H, Yokota A. Atlas hypoplasia manifesting as myelopathy in a child--case report. Neurol Med Chir (Tokyo) 2001; 41 (03) 160-162