Familial Chiari Malformation

Case Series

Benjamin D. Schanker, B.S.; Brian P. Walcott, M.D.; Brian V. Nahed, M.D.; Kristopher T. Kahle, M.D., Ph.D.; Yan Michael Li, M.D., Ph.D.; Jean-Valery C. E. Coumans, M.D.

Disclosures

Neurosurg Focus. 2011;31(3):e1 

In This Article

Abstract and Introduction

Abstract

Chiari malformations (Types I–IV) are abnormalities of the posterior fossa that affect the cerebellum, brainstem, and the spinal cord with prevalence rates of 0.1%–0.5%. Case reports of familial aggregation of Chiari malformation, twin studies, cosegregation of Chiari malformation with known genetic conditions, and recent gene and genome-wide association studies provide strong evidence of the genetic underpinnings of familial Chiari malformation. The authors report on a series of 3 family pairs with Chiari malformation Type I: 2 mother-daughter pairs and 1 father-daughter pair. The specific genetic causes of familial Chiari malformation have yet to be fully elucidated. The authors review the literature and discuss several candidate genes. Recent advances in the understanding of the genetic influences and pathogenesis of familial Chiari malformation are expected to improve management of affected patients and monitoring of at-risk family members.

Introduction

Chiari malformation can be a congenital or acquired condition in which the cerebellar tonsils protrude through the foramen magnum, and the disorder has traditionally been defined as downward herniation of the tonsils of 5 mm or more.[3] The size of the posterior fossa and the degree of stenosis also play a role in the development of symptoms. Patients may be asymptomatic, even when there is significant descent of the tonsils. Conversely, symptoms can appear when relatively minimal cerebellar displacement exists. While the rate of progression can vary, most patients experience chronic or exertional headaches, ocular disturbances, neck pain, scoliosis, cerebellar ataxia, and vertigo. This condition can also result in hydrocephalus or syringomyelia as the result of CSF pathway obstruction. The mean age of presentation is 24.9 ± 15.8 years.[27] Estimates suggest that approximately 215,000 Americans may be affected with CM, with or without syringomyelia.[35] The incidence of CM ranges between 1/18,000 and 1/1280, not correcting for the suspected underdiagnosis of asymptomatic patients due to a lack universal neuroimaging.[25,33,35] An estimated 65%–80% of patients with CM present with syringomyelia.[11,27] Traditionally, combined surgical decompression and enlargement of the posterior fossa is a common method of treatment, although patients may require additional care for syringomyelia and hydrocephalus. The decision to proceed with surgical intervention often depends on disease severity and/or progression.

Chiari malformations have long been considered sporadic conditions, without a heritable etiology. However, there have been a number of case reports identifying familial aggregation and clustering of CM, suggesting a genetic basis.[1,6–9,13,15,17,22,27,28,34,37–40,42,44,45,49,51,52] A recent large retrospective series of 500 cases spanning the past 2 decades found the prevalence of familial CM to be about 3%,[41] and a past study of 364 patients with CM found that 12% of patients had a close relative with CM and/or syringomyelia.[27] We report on a series of 3 family pairs in whom a CM was present (Table 1).

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