Neuroimaging findings in children with rare or novel de novo chromosomal anomalies.
BACKGROUND
De novo constitutional chromosomal anomalies provide important insights into the genetic loci responsible for congenital neurological disorders. However, most phenotypic descriptions of patients with rare chromosomal abnormalities are published as individual case reports or small group studies, making genotype-phenotype correlations unclear. Moreover, many clinical genetic reports do not include neuroimaging.


METHODS
We conducted a retrospective case series study of all children who had genetic testing done at Children's Memorial Hospital in Chicago, Illinois between 1985 and 2006. The case series was selected from a database containing all chromosomal testing results, clinical data, and neuroimaging. Clinical examination results were assigned by board certified geneticists and/or neurologists and neuroimages were reviewed by both a neurologist or neuroradiologist and a blinded neurologist.


RESULTS
Of the 28,108 children in the series, we identified 34 children with novel or apparently novel de novo chromosomal abnormalities. Several of the cases represent potentially new genetic loci for neurological malformations and novel syndromic conditions.


CONCLUSIONS
This study demonstrates the utility of large clinical databases in assessing genotype-phenotype correlations and mapping loci for congenital neurological disorders. We describe a case-series strategy to analyze existing databases to reveal new genotype-phenotype correlations.
Epstein
Leon G
LG
Northwestern University's Feinberg School of Medicine, Department of Pediatrics, Chicago, Illinois 60611, USA.
Jalali
Ali
A
Chary
Ajit N
AN
Khan
Sophia
S
Ross
Joshua
J
Coppinger
Justine
J
Carlson
Katrin
K
Charrow
Joel
J
Burton
Barbara
B
Zimmerman
Donald
D
Curran
John
J
Kim
Francine
F
Nguyen
Pam
P
Burrowes
Delilah
D
Angle
Brad
B
Stack
Cynthia
C
Shaffer
Lisa
L
Kessler
John A
JA
Bassuk
Alexander G
AG
D002648:Child; D002869:Chromosome Aberrations; D002885:Chromosomes, Human, Pair 16; D002886:Chromosomes, Human, Pair 17; D002887:Chromosomes, Human, Pair 18; D002896:Chromosomes, Human, Pair 6; D002897:Chromosomes, Human, Pair 7; D003952:Diagnostic Imaging; D005260:Female; D020869:Gene Expression Profiling; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007621:Karyotyping; D008297:Male; D009422:Nervous System Diseases / Q000000981:diagnostic imaging* / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011859:Radiography; D012189:Retrospective Studies