Child's Nervous System

, Volume 35, Issue 10, pp 1665–1671 | Cite as

Chiari malformation type I: what information from the genetics?

  • Valeria Capra
  • Michele Iacomino
  • Andrea Accogli
  • Marco Pavanello
  • Federico Zara
  • Armando Cama
  • Patrizia De MarcoEmail author
Special Annual Issue



Chiari malformation type I (CMI), a rare disorder of the craniocerebral junction with an estimated incidence of 1 in 1280, is characterized by the downward herniation of the cerebellar tonsils of at least 5 mm through the foramen magnum, resulting in significant neurologic morbidity. Classical CMI is thought to be caused by an underdeveloped occipital bone, resulting in a posterior cranial fossa which is too small to accommodate the normal-sized cerebellum. In this review, we dissect the lines of evidence supporting a genetic contribution for this disorder.


We present the results of two types of approaches: animal models and human studies encompassing different study designs such as whole genome linkage analysis, case-control association studies, and expression studies. The update of the literature also includes the most recent findings emerged by whole exome sequencing strategy.


Despite evidence for a genetic component, no major genes have been identified and the genetics of CMI is still very much unknown. One major challenge is the variability of clinical presentation within CMI patient population that reflects an underlying genetic heterogeneity.


The identification of the genes that contribute to the etiology of CMI will provide an important step to the understanding of the underlying pathology. The finding of a predisposing gene may lead to the development of simple and accurate diagnostic tests for better prognosis, counseling, and clinical management of patients and their relatives.


Chiari type I malformation (CMI) Syringomyelia (SM) Hindbrain Tonsillar ectopia Posterior cranial fossa (PCF)  Autosomal dominant/recessive inheritance Whole exome sequencing (WES) 


Funding information

This work was supported by Ricerca Corrente Ministero Salute-Italy 2016; M.I. is supported by Trust Volpati.

Compliance with ethical standards

Conflict of interest

The authors report no conflicts of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Valeria Capra
    • 1
  • Michele Iacomino
    • 1
    • 2
  • Andrea Accogli
    • 1
  • Marco Pavanello
    • 1
  • Federico Zara
    • 2
  • Armando Cama
    • 1
  • Patrizia De Marco
    • 2
    Email author
  1. 1.UOC NeurochirurgiaIRCCS Istituto Giannina GasliniGenoaItaly
  2. 2.UOSD Laboratorio Neurogenetica e NeuroscienzeIRCCS Istituto Giannina GasliniGenoaItaly

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