Is Chiari I malformation Hereditary? Part 1

Diane Mueller, ND, RN, FNP-BC

Many people with Chiari are curious to know if there is a genetic component, or if their children will ‘inherit’ the disorder.  Although there is no clear answer to the hereditary theory, there are a number of case reports in the English literature that describe familial patterns.

Atkinson, Kokmen & Miller (1998) presented a case report of monozygotic twin sisters with CMI and syringomyelia. The daughter of one twin also had CMI. The three family members underwent posterior fossa decompression. The authors postulated that occipital dysplasia and crowding of the posterior fossa may contribute to the associated tonsillar ectopia.

A case report was published by Mavinkurve, Sciubba, Amundson and Jallo (2005) that describes two sisters who initially presented with scoliosis at the time of their school physicals. Further investigation with MRI revealed CMI with syringomyelia.  Both girls underwent successful decompression surgery with resolution of the syringomyelia in both.

In 2006, Szewka, Walsh, Boaz, Carvalho & Golomb published a report of 3 families with CMI. The authors presented a mother/son, a set of monozygotic twins and two ½ siblings with two maternal cousins, all with CMI. The authors reviewed the literature for a pattern of inheritance.

Robenek, Kloska & Husstedt (2006) reported a sister and two ½ brothers all with syringomyelia and, in two cases, CMI. In this report, the mother did not have CM. The mother had a third son from a different father, without syringomyelia. The authors proposed an autosomal-dominant predisposition for the syringomyelia.

Three sisters diagnosed with symptomatic CMI with cervico-thoracic syrinx, and a fourth sister without radiographic evidence of CMI was reported by Weisfeld-Adams, Carter, Likeman, & Rankin (2007). A fourth sister did not have radiographic findings of CMI or syringomyelia. The mother had platybasic features on MRI and the father had no abnormal radiographic findings.

Tubbs, et al (2008) presented an analysis of the volumetric measurements among a multigenerational family with CMI. The family consisted of a great grandmother (diagnosed with CMI at autopsy), her daughter, the daughter’s son, daughter, and twin (monozygotic) sons. The measurement of tonsillar herniation among the family ranged from 6-25mm. All of the family members (except the great-grandmother) presented with symptoms consistent with CMI. After careful measurements of the posterior fossa, the authors concluded that there was no abnormal or reduced posterior fossa volume among the family members with CMI as compared to normal cohorts.

Family aggregation of 3 family pairs was presented by Shanker, et al (2011). The authors presented a case series of 2 mother-daughter pairs, and a father-daughter with CMI. All of the family members exhibited symptoms referable to CMI at time of diagnosis. The authors indicate experience with familial clustering in their practice, suggesting a genetic basis.

Considering the case reports sited above, in addition to many more published in the English literature, one might conclude that there is a familial preponderance for CMI. However, is there a true genetic factor that contributes to the likely-hood one will have radiographic findings of CMI? Part 2 of this blog will review some of the recent research on the genetic hypothesis of Chiari malformation and related disorders.

References

Atikinson J.L., Kokmen E., & Miller G.M., Evidence of posterior fossa hypoplasia in the familial variant of adult Chiari I malformation: case report. Neurosurgery, 1998, 42(2):401-403.

Mavinkurve G.G., Sciubba D., Amundson E., & Jallo G.I. Familial Chiari type I malformation with syringomyelia in two siblings: case report and review of the literature. Childs Nerv Syst , 2005, 21(11):955-959.

Szewka A.J., Walsh L.E., Boaz J.C., Carvalho K.S., & Golomb M. R. Chiari in the family: inheritance of the Chiari I malformation. Pediatric Neurology. 2006, June; 34(6):481-485.

Robenek M., Kloska S.P., & Husstedt I.W. Evidence of familial syringomyelia in discordant association with Chiari type I malformation. Eur J Neurol, 2006 July;13(7):783-785.

Weisfeld-Adams J.D., Carter M.R., Likeman M.J., Rankin J. Three sisters with Chiari I malformation with and without associated syringomyelia. Pediatr Neurosurg, 2007;43(6):533-538.

Tubbs R.S., Hill M., Loukas M., Shoja M.M., Oakes W. J. Volumetric analysis of the posterior cranial fossa in a family with four generations of the Chiari malformation type I. J Neurosurg Pediatrics, 2008; I:21-24.

Shanker B.D., et al. Familial Chiari malformation: case series. Neurosurg Focus, 2011;31(3):E1.