Transcript Velo-Cardio-Facial Syndrome - National Alliance for Medical Image

Velo-Cardio-Facial Syndrome
PRINCIPAL INVESTIGATOR:
Marek Kubicki, MD, PhD
INVESTIGATORS:
Zora Kikinis, PhD
Sylvain Bouix, PhD
Marc Niethammer, PhD
Martha Shenton, PhD
Christine Finn, MD
Raju Kucherlapati, MD
RESEARCH ASSISTANT:
Doug Markant, BA
National Alliance for Medical Image Computing
http://na-mic.org
AHM, SLC, January 2007
Velo-Cardio-Facial Syndrome (VCFS)
• Condition defined by Sphrintzen in 1978
• Chromosome 22 q11.2 deletion. Deletion of 1.5 to 3 Mb
(single copies of 30 to 45 genes missing)
• Prevalence 1 in every 4000 newborns
National Alliance for Medical Image Computing
http://na-mic.org
AHM, SLC, January 2007
VCFS Symptoms
• "velum" latin meaning soft palate
Cleft palate, small or aplastic tonsils,
hypernasal speech
• “kardia" greek meaning heart
VSD , right sided aortic arch, tetralogy
of Fallot, aberrant subclavian artery
• "facial" latin having to do with the face
maxillary excess, malar flatness, facial asymmetry, thin
upper lip, prominent nasal root, large nasal tip, pinched,
hypoplastic base
National Alliance for Medical Image Computing
http://na-mic.org
AHM, SLC, January 2007
Common Cognitive Deficits in VCFS
• Psychomotor and perceptual deficits
• Learning and memory disabilities
• Emotional abnormalities (flat affect and poor
social interaction).
• High incidence for schizophrenia and/or
bipolar disorder in adult (30% VCFS patients
develop schizophrenia)
National Alliance for Medical Image Computing
http://na-mic.org
AHM, SLC, January 2007
Neuroimaging Findings in VCFS
•
MRI case reports (most)
- high frequency of nonspecific white matter hyperintensities (30% of cases)
- cavum septi pellucidi (in 45% of cases)
•
MRI quantitative reports (few)
- Reduced volumes of regions related to language and verbal memory (superior
temporal gyrus, hippocampus, amygdala and parietal lobe).
- Increased volume and posterior displacement of the corpus callosum
•
DTI (two studies)
- Reduced anisotropy in frontal, parietal, and temporal white matter
- Reduced anisotropy in white matter tracts connecting frontal and temporal lobes
- Reduced anisotropy in inferior parietal lobule which is correlated with scores from the
arithmetic subscale of the WISC/WAIS, after co-varying for IQ and age of subjects.
National Alliance for Medical Image Computing
http://na-mic.org
AHM, SLC, January 2007
Neuroimaging Findings in VCFS
Cases with Schizophrenia
•
MRI (3 studies, only one with IQ matched populations)
- Decreased total gray and white matter volumes
- Increased total and sulcal CSF volumes.
- Decreased frontal, temporal and parietal gray matter volumes
- Increased corpus callosum volume
Based on scarce findings, VCFS investigators proposed a model, in which a deficiency
in frontal maturation leads to a vulnerability for schizophrenia among individuals with
VCFS
•
DTI
- None
National Alliance for Medical Image Computing
http://na-mic.org
AHM, SLC, January 2007
VCFS Schizophrenia Candidate Genes
• COMT (controls dopamine degradation in prefrontal
cortex, related to attention and memory)
• RTN4R (also known as Nogo-66 Receptor, related to
axonal regeneration and plasticity as well as myelin)
• PRODH (one of the enzymes to convert proline to
glutamate)
• ZDH8
• SNAP29
• TBX1
National Alliance for Medical Image Computing
http://na-mic.org
AHM, SLC, January 2007
Project
• Subject recruitment
• Psychological interview
• DNA analysis, genotyping of the
22q11.2 region
• Brain imaging (MRI and DTI on 3T)
• Analysis of imaging data, and genetic
correlations
National Alliance for Medical Image Computing
http://na-mic.org
AHM, SLC, January 2007
Aims
• Etiology of schizophrenia and
related diseases
• Prognosis of mental health diseases
in VCFS
• Early intervention
National Alliance for Medical Image Computing
http://na-mic.org
AHM, SLC, January 2007
Hypotheses
Regions that we want to study with MRI
-
DLPC (COMT)
-
Orbital Frontal Gyrus (emotion)
-
Cingulate Gyrus (attention, emotion)
-
Hippocampus (memory, learning)
Tracts that we want to study with DTI
-
Fornix (memory)
-
Arcuate Fasciculus (language)
-
Cingulum Bundle (attention)
-
Uncinate Fasciculus (emotion, affective flattening)
National Alliance for Medical Image Computing
http://na-mic.org
AHM, SLC, January 2007
Potential Challenges for Atlas Based
Scripts
• Brain atrophy
• Congenital abnormalities
• Brain asymmetry
• White matter lesions
National Alliance for Medical Image Computing
http://na-mic.org
AHM, SLC, January 2007
Velo-Cardio-Facial Syndrome (VCFS)
as a Genetic Model for Schizophrenia.
PRINCIPAL INVESTIGATOR:
Marek Kubicki, MD, PhD
INVESTIGATORS:
Zora Kikinis, PhD
Sylvain Bouix, PhD
Marc Niethammer, PhD
Christine Finn, MD
Raju Kucherlapati, MD
Martha Shenton, PhD
RESEARCH ASSISTANT:
Doug Markant, BA
BACKGROUND:
•
VCFS is a rare genetic syndrome (single
copies of 30-45 genes on 22 chromosome
are missing)
•
30% of patients with VCFS develop
schizophrenia
AIMS:
•
To characterize anatomical similarities and
dissimilarities between VCFS and
Schizophrenia
•
To find “schizophrenia” genes
DATA:
•
National Alliance for Medical Image Computing
http://na-mic.org
DTI, MRI, haplotypes, neuropsychology
AHM, SLC, January 2007