Neurology Publish Ahead of PrintDOI: 10.1212/WNL.0000000000010856

Teaching NeuroImages: CLOVES syndrome

Authors: Meagan Collins, BS* ; Eric Krochmalnek, BS*; Sarah Alsubhi, MD; Myriam Srour, MD, PhD

*Co-first authors

Meagan Collins*, Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada, CHU Sainte Justine Research Center, Université de Montréal, Montreal, QC, Canada Eric Krochmalnek* , Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada Sarah Alsubhi, Department of Pediatrics, Division of Pediatric Neurology, McGill University, Montreal, QC, Canada Myriam Srour, Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada, Department of Pediatrics, Division of Pediatric Neurology, McGill University, Montreal, QC, Canada Search Terms: Clinical neurology examination, Cortical dysplasia, CLOVES, Hemimegalencephaly, PIK3CA Neurology® Published Ahead of Print articles have been peer reviewed and accepted for

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Published Ahead of Print on December 1, 2020 as 10.1212/WNL.0000000000010856

Title Character count: 26 Number of Tables: 0 Number of Figures: 1 Word count of Abstract: N/A Word Count of Paper: 104 Corresponding Author: Myriam Srour, myriam.srour@mcgill.ca Disclosure: The authors report no dislcosures relevant to the manuscript. Study Funding: No targeted funding reported. This 17-year-old male is diagnosed with congenital lipomatous overgrowth with vascular,

epidermal, skeletal and spinal anomalies (CLOVES) syndrome1, mainly affecting his right face,

brain and trunk (MIM#612918) (Figure 1.A-C). Brain MRI revealed right hemimegalencephaly

with extensive temporo-parieto-occipital cortical dysplasia (Figure 1.D1-4). He developed

neonatal drug-resistant seizures requiring right hemispherectomy at 15 months. He has left

hemiparesis and intellectual disability. CLOVES syndrome is a segmental overgrowth syndrome

associated with somatic hyperactivating mutations in PIK3CA, belonging to the

PI3K/AKT/mTOR signaling pathway2. Genetic testing on buccal swab revealed a pathogenic

somatic missense mutation in PIK3CA (NM_006218.4:c.1624G>A,p.Glu542Lys) at an alternate

allele frequency of 4.5%, which was absent in blood.

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Appendix 1. Authors

Name Location Contribution Meagan Collins, BS Child Health and Human

Development Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada CHU Sainte Justine Research Center, Université de Montréal, Montreal, QC, Canada

Drafting/revising the manuscript, study concept or design, accepts responsibility for conduct of research and final approval, acquisition of data, study supervision

Eric Krochmalnek, BS Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada

Drafting/revising the manuscript, study concept or design, accepts responsibility for conduct of research and final approval, acquisition of data, study supervision.

Sarah Alsubhi, MD Department of Pediatrics, Division of Pediatric Neurology, McGill University, Montreal, QC, Canada

Drafting/revising the manuscript, study concept or design, accepts responsibility for conduct of research and final approval, acquisition of data, study supervision

Myriam Srour, MD, PhD

Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada Department of Pediatrics, Division of Pediatric Neurology, McGill University, Montreal, QC, Canada

Drafting/revising the manuscript, study concept or design, accepts responsibility for conduct of research and final approval, acquisition of data, study supervision

Acknowledgments: The authors thank the parents for their contribution to this study.

Teaching Slides - http://links.lww.com/WNL/B224

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References

1. Gucev, Z. S., Tasic, V., Jancevska, A., Konstantinova, M. K., Pop-Jordanova, N., Trajkovski, Z., Biesecker, L. G. Congenital lipomatosis overgrowth, vascular malformations, and epidermal nevi (CLOVE) syndrome: CNS malformations and seizures may be a component of this disorder. Am. J. Med. Genet. 146A: 2688-2690, 2008.

2. Kurek, K. C., Luks, V. L., Ayturk, U. M., Alomari, A. I., Fishman, S. J., Spencer, S. A., Mulliken, J. B., Bowen, M. E., Yamamoto, G. L., Kozakewich, H. P. W., Warman, M. L. Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome. Am. J. Hum. Genet. 90: 1108-1115, 2012.

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Figure Legend

Figure 1. Clinical and radiological findings

(A) Right hemifacial overgrowth in our patient with CLOVES syndrome. (B) Epidermal nevus on right face and neck. (C) The epidermal nevus on the trunk, characterized by hyperpigmentation and epidermal thickening, follows Blaschko lines and suggests the presence of an underlying somatic mutation. (D.a-D.d) Axial 1.5T brain MRI at the age of 2 months reveals right hemimegalencephaly, enlarged right ventricle, and extensive cortical dysplasia in the right temporal, parietal and occipital lobes. There is blurring of the grey-white border and polymicrogyric appearance of the cortex. Note the lipomatous overgrowth of the right face (arrowhead) (D.a).

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DOI 10.1212/WNL.0000000000010856 published online December 1, 2020Neurology

Meagan Collins, Eric Krochmalnek, Sarah Alsubhi, et al. Teaching NeuroImages: CLOVES syndrome

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