Evidence for a Genetic Component in Chiari Malformation Type I With or Without Syringomyelia

While little is known about the developmental causes of Chiari Malformation Type I or syringomyelia, there is evidence of familial aggregation, suggesting genetics may be important. In the early 1990’s, there were several reports of familial cases of CMI, including two affected siblings, 5 identical twins, 11 and identical triplets. 2 A more recent twin study examined 6 additional sets of twins and reported a higher concordance between identical twins when compared with fraternal twins (Speer et al , 2003). Because identical twins arise from the same gamete and fraternal twins arise from two separate gametes, the higher concordance rate in identical twins is support that genetic factors contribute to CMI. In another study of 364 CMI patients, 12% reported having at least one close relative with CMI and/or syringomyelia. 7 Thus, familial clustering occurs in at least a subset of CMI patients.

Another clue that genetics may be important for risk to develop CMI is that it has been associated with other genetic conditions. Many of the known genetic disorders that co-segregate with CMI affect mesodermally derived cartilage and/or bone such as achondroplasia, Klippel Feil sequence, Hadju-Cheney syndrome, Albright Hereditary Osteodystrophy (pseudohypoparathyroidism), familial hypophosphatemia rickets, and spondylo-epiphyseal dyplasia tarda. 4,8 CMI is also associated with syringohydromyelia, hydrocephalus, and several other disorders that cause malformations of the skull and cervical spine. 3,6,12

Further, the identification of a heritable form of CMI in cavalier King Charles spaniels provides more evidence for a genetic basis, and may also provide an important animal model for further investigation of the relevance of identified genes and/or treatment strategies. 9

The important work of finding the specific genes associated with CMI has only just begun. One study found that MRI measurements from the skull of CMI family members were highly correlated, particularly the volume of the posterior fossa. 1 Perhaps surprisingly, the degree of cerebellar tonsil herniation was not heritable. Boyles and colleagues1 also conducted a genome screen in twenty-three families with multiple individuals affected with CMI. They found significant evidence for a gene associated with CMI on chromosomes 9 and 15.

In summary, the etiology of CMI is complex and has an important genetic component. The specific genes involved have not yet been identified and the proportion of CMI families with genetic causes is unknown. However, this is an active area of research ( http://www.chg.duke.edu/diseases/chiari.html ).


  1. Boyles AL, Enterline DS, Hammock PH, et al. Phenotypic definition of Chiari type I malformation coupled with high-density SNP genome screen shows significant evidence for linkage to regions on chromosomes 9 and 15. Am J Med Genet A. 2006;140(24):2776-85.
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  5. Herman MD, Cheek WR, StorrsBB. Two siblings with the Chiari 1 malformation. Pediatric Neurosurgery 1990;16:183-184.
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  7. Milhorat TH, Chou MW, Trinidad EM, et al. Chiari I malformation redefined: clinical and radiographic findings for 364 symptomatic patients. Neurosurgery 1999;44:1005-1017.
  8. Pauli RM, Horton VK, Glinski LP, Reiser CA. Prospective assessment of risks for cervicomedullary-junction compression in infants with achondroplasia. Am J Hum Genet 1995;56:732-744.
  9. Rusbridge C, Knowler SP. Hereditary aspects of occipital bone hypoplasia and syringomyelia (Chiari type I malformation) in cavalier King Charles spaniels. Veterinary Record 2003;153:107-112.
  10. Speer MC, Enterline DS, Mehltretter L, et al. Chiari type I malformation with or without syringomyelia: Prevalence and genetics. Journal of Genetic Counseling 2003;12:297-311.
  11. Stovner LJ. Headache and chiari type 1 malformation: occurrence in female monozygotic twins and first-degree relatives. Cephalalgia 1992;12:304-307.
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Revised 05/2010

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