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Chiari I malformation in patients with RASopathies

  • Case-Based Review
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Abstract

Purpose

Chiari I malformation (CIM) is a common pediatric neurologic anomaly which could be associated with a variety of genetic disorders. However, it is not always clear whether the observed associations between CIM and RASopathies are real or random. The knowledge of the real association could provide useful guidance to clinicians. Furthermore, it could help to better understand the still unknown genetic etiology of CIM.

Method and results

We reviewed the current knowledge of CIM and RASopathies in the paper. Here, we describe one patient with CIM and Noonan syndrome and three patients with CIM and neurofibromatosis type 1. Three of the four patients underwent standard surgical therapy of Chiari decompression and had a straightforward recovery without further complications from surgery.

Conclusion

In RASopathy, imaging of the nervous system may be necessary. With the increase in availability of magnetic resonance imaging, we believe that there will be a growing body of evidence to suggest that CIM is more commonly seen in RASopathy. Future studies should attempt to elucidate the pathogenic mechanism responsible for CIM mediated by the RAS/MAPK signaling pathway.

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References

  1. Ueda K, Yaoita M, Niihori T, Aoki Y, Okamoto N (2017) Craniosynostosis in patients with RASopathies: accumulating clinical evidence for expanding the phenotype. Am J Med Genet A 173:2346–2352

    Article  CAS  Google Scholar 

  2. Aoki Y, Niihori T, Inoue S, Matsubara Y (2016) Recent advances in RASopathies. J Hum Genet 61:33–39

    Article  CAS  Google Scholar 

  3. Saletti V, Viganò I, Melloni G, Pantaleoni C, Vetrano IG, Valentini LG (2019) Chiari I malformation in defined genetic syndromes in children: are there common pathways? Childs Nerv Syst 35:1727–1739

    Article  Google Scholar 

  4. Speer MC, George TM, Enterline DS, Franklin A, Wolpert CM, Milhorat TH (2000) A genetic hypothesis for Chiari I malformation with or without syringomyelia. Neurosurg Focus 8(3):E12

    Article  CAS  Google Scholar 

  5. Markunas CA, Lock E, Soldano K, Cope H, Ding CK, Enterline DS, Grant G, Fuchs H, Ashley-Koch AE, Gregory SG (2014) Identification of Chiari type I malformation subtypes using whole genome expression profiles and cranial base morphometrics. BMC Med Genet 7:39

    Google Scholar 

  6. Keh YS, Abernethy L, Pettorini B (2013) Association between Noonan syndrome and Chiari I malformation: a case-based update. Childs Nerv Syst 29:749–752

    Article  Google Scholar 

  7. Milhorat TH, Nishikawa M, Kula RW, Dlugacz YD (2010) Mechanisms of cerebellar tonsil herniation in patients with Chiari malformations as guide to clinical management. Acta Neurochir 152:1117–1127

    Article  Google Scholar 

  8. Nishikawa M, Sakamoto H, Hakuba A, Nakanishi N, Inoue Y (1997) Pathogenesis of Chiari malformation: a morphometric study of the posterior cranial fossa. J Neurosurg 86:40–47

    Article  CAS  Google Scholar 

  9. Gripp KW, Hopkins E, Doyle D, Dobyns WB (2010) High incidence of progressive postnatal cerebellar enlargement in Costello syndrome: brain overgrowth associated with HRAS mutations as the likely cause of structural brain and spinal cord abnormalities. Am J Med Genet A 152A:1161–1168

    Article  Google Scholar 

  10. Gripp KW, Hopkins E, Sol-Church K, Stabley DL, Axelrad ME, Doyle D, Dobyns WB, Hudson C, Johnson J, Tenconi R, Graham GE, Sousa AB, Heller R, Piccione M, Corsello G, Herman GE, Tartaglia M, Lin AE (2011) Phenotypic analysis of individuals with Costello syndrome due to HRAS p.G13C. Am J Med Genet A 155A:706–716

    Article  Google Scholar 

  11. Tubbs RS, Beckman J, Naftel RP, Chern JJ, Wellons JC 3rd, Rozzelle CJ, Blount JP, Oakes WJ (2011) Institutional experience with 500 cases of surgically treated pediatric Chiari malformation type I. J Neurosurg Pediatr 7:248–256

    Article  Google Scholar 

  12. Tubbs RS, Rutledge SL, Kosentka A, Bartolucci AA, Oakes WJ (2004) Chiari I malformation and neurofibromatosis type 1. Pediatr Neurol 30:278–280

    Article  Google Scholar 

  13. Ejarque I, Millán-Salvador JM, Oltra S, Pesudo-Martínez JV, Beneyto M, Pérez-Aytés A (2015) Arnold-Chiari malformation in Noonan syndrome and other syndromes of the RAS/MAPK pathway. Rev Neurol 60:408–412

    PubMed  Google Scholar 

  14. Yoon G, Rosenberg J, Blaser S, Rauen KA (2007) Neurological complications of cardio-facio-cutaneous syndrome. Dev Med Child Neurol 49:894–899

    Article  Google Scholar 

  15. Poretti A, Ashmawy R, Garzon-Muvdi T, Jallo GI, Huisman TA, Raybaud C (2016) Chiari type 1 deformity in children: pathogenetic, clinical, neuroimaging, and management aspects. Neuropediatrics 47:293–307

    Article  Google Scholar 

  16. McClugage SG, Oakes WJ (2019) The Chiari I malformation. J Neurosurg Pediatr 24:217–226

    Article  Google Scholar 

  17. Greenlee JD, Donovan KA, Hasan DM, Menezes AH (2002) Chiari I malformation in the very young child: the spectrum of presentations and experience in 31 children under age 6 years. Pediatrics 110:1212–1219

    Article  Google Scholar 

  18. Pozetti M, Belsuzarri TA, Belsuzarri NC, Seixas NB, Araujo JF (2016) Neurofibromatosis type 1 and Chiari type 1 malformation: a case report and literature review of a rare association. Surg Neurol Int 7(Suppl 16):S469–S472

    PubMed  PubMed Central  Google Scholar 

  19. Schwartz NS, Regelmann MO (2019) Precocious puberty and Chiari I malformation with syrinx: a case report of an unusual presentation of Costello syndrome. Int J Pediatr Endocrinol 2019:2

  20. Hara H, Arakawa H (2005) Coexistence of neurofibromatosis 1 and Chiari type I malformation: an unusual association. J Dermatol 32:34–37

    Article  Google Scholar 

  21. Ratner N, Miller SJ (2015) A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor. Nat Rev Cancer 15:290–301

    Article  CAS  Google Scholar 

  22. Leon TJ, Kuhn EN, Arynchyna AA (2019) Patients with “benign” Chiari I malformations require surgical decompression at a low rate. J Neurosurg Pediatr 23:498–506

    Article  Google Scholar 

  23. Tidyman WE, Rauen KA (2008) Noonan, Costello and cardio-facio-cutaneous syndromes: dysregulation of the Ras-MAPK pathway. Expert Rev Mol Med 10:e37

    Article  Google Scholar 

  24. Roberts PJ, Der CJ (2007) Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 26(22):3291–3310

    Article  CAS  Google Scholar 

  25. Tubbs RS, Doyle S, Conklin M, Oakes WJ (2006) Scoliosis in a child with Chiari I malformation and the absence of syringomyelia: case report and a review of the literature. Childs Nerv Syst 22:1351–1354

    Article  Google Scholar 

  26. Hankinson T, Shane Tubbs R, Wellons JC (2011) Duraplasty or not? An evidence-based review of the pediatric Chiari I malformation. Childs Nerv Syst 27:35–40

    Article  Google Scholar 

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Funding

The study was supported by the Science and Education Program of Suzhou (KJXW2017023).

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Authors and Affiliations

  1. Department of Neurosurgery, Children’s Hospital of Soochow University, 92 Zhongnan Street, Suzhou, 215006, Jiangsu, People’s Republic of China

    Yong Han, Min Chen & Hangzhou Wang

Authors
  1. Yong Han
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  2. Min Chen
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  3. Hangzhou Wang
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Corresponding author

Correspondence to Hangzhou Wang.

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Conflict of interest

The authors received no financial and/or material support for the research reported in this paper. The authors state that there are no conflicts of interest arising from the research reported in this paper.

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Written informed consent was obtained from the patients for the publication of these cases and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

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Yong Han is the first author.

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Han, Y., Chen, M. & Wang, H. Chiari I malformation in patients with RASopathies. Childs Nerv Syst 37, 1831–1836 (2021). https://doi.org/10.1007/s00381-020-05034-2

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  • DOI: https://doi.org/10.1007/s00381-020-05034-2

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