- Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY, USA
- Department of Neurosurgery, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
- Flaum Eye Institute - Department of Ophthalmology, University of Rochester Medical Center, Rochester, NY, USA
Anthony L. Petraglia
Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY, USA
DOI:10.4103/2152-7806.92165Copyright: © 2012 Petraglia AL. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
How to cite this article: Petraglia AL, Chengazi HU, Chung MM, Silberstein HJ. Leber congenital amaurosis associated with Chiari I malformation: Two cases and a review of the literature. Surg Neurol Int 21-Jan-2012;3:4
How to cite this URL: Petraglia AL, Chengazi HU, Chung MM, Silberstein HJ. Leber congenital amaurosis associated with Chiari I malformation: Two cases and a review of the literature. Surg Neurol Int 21-Jan-2012;3:4. Available from: http://sni.wpengine.com/surgicalint_articles/leber-congenital-amaurosis-associated-with-chiari-i-malformation-two-cases-and-a-review-of-the-literature/
Objective:Leber congenital amaurosis (LCA) is a rare, clinically and genetically heterogeneous disorder characterized by severe loss of vision in the first year of life, affecting approximately 3000 people in the United States. Some LCA patients manifest developmental abnormalities of the central nervous system (CNS) and neuroradiological studies have revealed a variety of cerebral anomalies in association with LCA; however, Chiari I malformations (CMI) have never been described.
Case Description:We report two sisters who were referred to the pediatric neurosurgery clinic for evaluation of CMI. The elder sister presented with convergence nystagmus from 3 months of age and magnetic resonance imaging (MRI) demonstrated evidence of significant CMI. Her younger sister began developing nystagmus at 4 months of age. Both had symptomatic progression and underwent suboccipital decompression. Both were subsequently diagnosed with LCA. Case specifics and imaging findings are presented.
Conclusions:CMI have been found in association with several genetic syndromes, but not with LCA. These patients represent the first reported cases of CMI with LCA and suggest an additional potential CNS anomaly. The unique occurrence in siblings and the association with another inherited disorder are suggestive of a genetic basis for CMI.
Keywords: Chiari I malformation, children, genetics, Leber congenital amaurosis
Leber congenital amaurosis (LCA) is a rare, clinically and genetically heterogeneous, autosomal recessive disorder that affects approximately 3000 people in the United States.[
Chiari I malformation (CMI) is a condition in which part of the skull is abnormally small or misshapen, resulting in a downward displacement of the cerebellar tonsils through the foramen magnum. Based on analysis of familial aggregation, an underlying genetic basis for CMI has been suggested.[
The elder sister initially presented with convergence nystagmus at age 3 months. By 5 months of age, her nystagmus was worsening and an MRI of her head demonstrated CMI. She was referred to the University of Rochester Pediatric Neurosurgery clinic at 1 year of age. The patient still had a prominent nystagmus and had now developed photophobia. She was also was noted to be gagging frequently (four to five times) with every meal. On examination, she was active and playful. She was able to pull to standing and had good motor strength. Her toes were downgoing bilaterally. She appeared to track well in all visual fields, although was noted to be squinting with the lights in the room. A repeat MRI of her head [Figure
(a–d) Case 1: Pre- and postoperative MRI images. Preoperative (a) sagittal T1-weighted and (b) axial T2-weighted MRI images demonstrating downward displacement of the cerebellar tonsils by approximately 8 mm, consistent with Chiari Type I malformation. Postoperative (c) sagittal T1-weighted and (d) axial T2-weighted images demonstrating adequate decompression
Due to her worsening symptoms, she underwent a suboccipital decompression. Briefly, the patient was positioned prone on the pediatric horseshoe. A linear skin incision was marked out commensurate with the spinous process of C2 through the inion. A standard sub-periosteal dissection was performed. Using an air drill, a cutting bur, and a diamond bur, the lamina of C1 was thinned out, as was the suboccipital bone adjacent to the foramen magnum. Utilizing a curette as well as small Kerrison and Fulton rongeurs, the C1 arch was removed laterally to the level of the lateral masses. In addition, the suboccipital bone was removed approximately 1.5 cm back from the posterior lip of the foramen magnum and bone removal was carried out to the lateral aspect of the foramen magnum as well. Dense scar tissue was taken off the dura, and while the dura was noted to expand somewhat, it was felt that the dura needed to be opened. The dura was opened in a Y-shape fashion and the arachnoid layer was preserved. A small piece of Gelfoam was placed over the dural defect and arachnoid layer, with no dural patch used. The wound was then closed in layers and the patient tolerated the procedure well. Her symptoms initially improved, but then returned to a lesser degree. Postoperative MRI imaging revealed adequate decompression [Figure
The patient went on to develop some neurobehavioral symptoms not typical for CMI, such as head banging. She was sent for ophthalmologic examination for her nystagmus, photophobia, and difficulty with learning colors. Dilated retinal examination revealed a normal appearing fundus [
The younger sister presented with nystagmus at 4 months of age. Examination revealed swirling, searching nystagmus. She did not exhibit gagging, fussiness, or head banging, but her parents reported poor visual behavior at home. She was seen in consultation with ophthalmology and was determined to have LCA. She was sent for an MRI of her head given her sister's prior medical history and progression. The MRI of her head (not shown) demonstrated evidence of cerebellar ectopia of the tonsils descending down to the level of C1 (approximately 9 mm), although she appeared to have more space at the foramen magnum relative to her sister at 1 year of age. Given her sister's experience and the patient's relatively benign presentation, we elected to clinically observe the patient rather than surgically decompress the CMI.
By 9 months of age, however, she began to experience gagging with meals and the patient was evaluated by a pediatric neurosurgeon at another institution closer to their home. An MRI of her head was repeated and demonstrated further cerebellar displacement, now measuring approximately 14 mm. She underwent surgical decompression for her CMI and has done well postoperatively thus far regarding those symptoms; however, her vision has continued to deteriorate.
LCA is the earliest and most severe form of all inherited retinal dystrophies, responsible for 10–18% of cases of congenital blindness.[
At least 14 genes have been associated with LCA, with mutations in the most common 9 genes accounting for approximately 70% of cases, and with 30% of cases whose causative genes are as yet undiscovered.[
CMI is a congenital abnormality of the brain, resulting in the displacement of the cerebellar tonsils through the foramen magnum. The condition can cause obstruction of CSF flow (resulting in a non-communicating hydrocephalus), as well as headaches, fatigue, nystagmus, difficulty swallowing, dizziness, nausea, impaired coordination, and in severe cases, paralysis. Visual symptoms have been described in CMI as well.[
We have reported here two sisters who presented to our clinic with symptoms concerning for symptomatic CMI but not dissimilar from those observed in some patients with LCA. Both patients were finally diagnosed with LCA as their vision deteriorated and formal ophthalmologic examinations were pursued. While CNS abnormalities are known to be associated with LCA, these patients represent the first reported cases of CMI in LCA and suggest an additional potential CNS anomaly. The association further suggests a genetic etiology of CMI. While a sporadic occurrence of CMI in these two sisters is possible, the previously reported familial aggregation pattern of CMI and its unique occurrence in these siblings with a known rare inherited disorder further supports the notion of a genetic basis for some forms of CMI. This observation is clearly limited by the number of patients in this report. However, the findings are intriguing nonetheless and the potential overlap that may exist between these two conditions necessitates further investigation.
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