Advisor: Igor NestrasilThis research was supported by the Undergraduate Research Opportunities Program (UROP)

Nestrasil, Igor

Nguyen, Carol

Paulson, Amy

Rizzo, William

University of Minnesota Digital Conservancy

Investigation of Alterations in Brain White Matter of Individuals Diagnosed with 
Smith-Lemli-Opitz Syndrome and Sjögren-Larsson Syndrome
METHODS
CONCLUSIONSRESULTS
REFERENCES
Figure 6. Ratio of cerebellar white matter to total 
intracranial volume across age
Background
Acknowledgements
Figure 9. Average cortical thickness versus age
Figure 7. Ratio of cerebral white matter to total 
intracranial volume across age
Undergraduate Research Opportunities Program,
National Institute of Health (NIH): 2U54HD061939-06,
Shire, 
Department of Pediatrics: Nestrasil Laboratory, 
Center for Neurobehavioral Development, 
Center for Magnetic Resonance Research,
Minnesota Supercomputing Institute 
Contact information: Amy Paulson, pauls860@umn.edu
Igor Nestrasil, nestr007@umn.edu
Smith-Lemli-Opitz Syndrome (SLOS) and 
Sjögren-Larsson Syndrome (SLS)
are sterol and isoprenoid disease caused 
by recessive autosomal mutations to 
genes DHCR7 and ALDH3A2 respectively. 
Both mutations cause disruption of lipid 
biosynthesis.
Clinical symptoms:
Neurological
Cognitive 
Physical
Currently, there is no cure for either 
disorder.
Recent incorporation of Magnetic 
Resonance Imaging (MRI) in the 
investigation of SLOS and SLS has 
resulted in evidence suggesting brain 
atrophy and decreases in white matter 
density with progression of the diseases; 
however, it has never been quantitatively 
studied.
SLS and SLOS affected individuals displayed lower 
volumetric values of cerebellar white matter compared to 
controls. Difference in cerebellar white matter between 
SLOS + SLS and controls was found to be statistically 
significant with a p < 0.001 (Figure 6).
Volumetric values for cerebral white matter were 
consistent between SLS, SLOS, and healthy control 
subjects (Figure 7). 
Estimated means of cerebellar white matter volume 
showed statistically relevant differences, p < 0.001 
(Figure 8).
Average cortical thickness displayed a declining value 
with respect to age (Figure 9).
Study participants:
SLOS (n=2) and SLS (n=16) subjects, healthy 
controls (n=97)
MRI image analysis:
T1-weighted images were processed through 
FreeSurfer (FS) Image Analysis Suite version 5.3
Statistics:
t-test with unequal variance and Welch degrees of 
freedom was used to evaluate discrepancies 
between SLOS + SLS patients and controls
Separating each of the group, a one way ANOVA 
was used to assess statistical significance
A univariate analysis of variance was used to control 
for the covariate of age
Comparisons of individuals with SLS, SLOS, and 
healthy controls revealed lower cerebellar white 
matter volume across age.
Lower cerebellar volumes in SLOS and SLS 
individuals suggest a possible cerebellar 
involvement.
Cortical thickness and cerebral white matter volumes 
for individuals with SLOS, SLS, and healthy controls 
illustrated a typical pattern seen in normally 
developing brains. 
Future directions:
Analysis of longitudinal MRI data.
Employing techniques sensitive to white matter 
microstructure and neuronal integrity such as 
diffusion tensor imaging and magnetic resonance 
spectroscopy.
1. Kanungo, S., Soares, N., He, M., & Steiner, R. D. (2013). Sterol metabolism disorders and 
neurodevelopment-an update. Developmental Disabilities Research Reviews,17(3), 197-210. 
doi:10.1002/ddrr.1114
2. Lee, R.W.Y., Conley, S. K., Gropman, A., Porter, F.D., Baker, E. H. (2013). Brain magnetic resonance 
imaging findings in Smith-Lemli-Opitz syndrome. American Journal of Medical Genetics, 161A(10), 
2407-2419. doi:10.1002/ajmg.a.36096
3. Srinivasan, G., Ushanandhini, P., Srividya, S., & Ramprabhanath, S. (2009). Typical neuroradiological 
features of Sjogren-Larsson Syndrome. The Neuroradiology Journal, 22(2), 169-173. 
doi:10.1177/197140090902200205
Objective
Hypotheses
To monitor the white and gray matter 
alteration in individuals diagnosed with 
SLOS and SLS by the use of quantitative 
MRI.
1. We predict lower white matter volumes 
in SLOS and SLS when compared to 
healthy controls.
2. We anticipate a decrease in white 
matter volume over time in SLOS and 
SLS patients with longitudinal follow-up. 
Figure 4. FS segmented 
brain, pial white matter 
surface
Figure 5. FS 3D surface 
model
Figure 1. T1-weighted image in three anatomical planes; 
SLS male, 7 year old
Figure 3. FS pial and white 
matter surface
Amy Paulson1, Carol Nguyen1, William Rizzo2, Igor Nestrasil1
1. University of Minnesota Department of Pediatrics, 2. University of Nebraska Medical Center Department of Pediatrics
Figure 2. T1-weighted image in three anatomical planes; 
healthy control male, 7 year old
Figure 8. Comparison of total cerebellar white matter 
volume between patient groups 


Investigation of Alterations in Brain White Matter of Individuals Diagnosed with Smith-Lemli-Opitz Syndrome and Sjögren-Larsson Syndrome

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Investigation of Alterations in Brain White Matter of Individuals Diagnosed with Smith-Lemli-Opitz Syndrome and Sjögren-Larsson Syndrome

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