Abstract Details

Title Clinical, Radiological and Genetic Results in a Cohort of 50 Patients with Nonsyndromic and Syndromic Polymicrogyria

Topic Child Neurology/Developmental Neurobiology

Presentation(s) S25 - (-)

Poster/Presentation
Number 005

Objective

Background Common clinical features of PMG include seizures, developmental delay, oromotor dysfunction and motor disabilities. PMG is a malformation of cortical development characterized by numerous small gyri that can be attributed to environmental causes, single gene disorders with various patterns of inheritance, or chromosomal rearrangements, usually sporadic.

Design/Methods Inclusion of any type of PMG, excluding confirmed congenital CMV/toxoplasmosis. We performed detailed review of medical records; karyotype and/or CGH and/or genomic SNP microarray; and specific gene analysis when indicated.

Results We studied 46 sporadic patients and two families with two siblings each. Their PMG pattern was variable. 24/50 (48%) had associated brain malformation(s), including 5/24 nodular heterotopia , 4/24 microcephaly, 2/24 corpus callosum dysgenesis, 2/24 brainstem hypoplasia, 2/24 hemimegalencephaly, 1/24 focal cortical dysplasia, 1/24 optic chiasm hypoplasia. 10/50 (20%) had PMG as part of a syndrome. One karyotype showed a reciprocal translocation 46,XY t(8;22)(p23.1;p11.2). Of 27 CGH microarray results, 23 (85%) were normal. The detected CGH anomalies included a 22q11del, 1p36del, a 2p21del of unknown significance, and a 2p13.3-p16.3duplication. We fine mapped a subgroup of bilateral perisylvian polymicrogyria (BPP) patients to 2p16.1-p16.3. We identified a novel TUBB2B mutation in exon 4 in a sporadic patient with PMG and associated anomalies of the basal ganglia and brainstem; neither parent carried this mutation.

Conclusions Polymicrogyria is markedly heterogeneous. Our results support previous suggestions of PMG loci on chromosomes 22q11 and 1p36. We have narrowed a novel locus for BPP to 2p13.1-p16.3. These data can help to identify the causative genes located in these regions. We found a novel and de novo TUBB2B mutation in a patient with complex PMG. Identification of associated brain malformations and phenotypic anomalies can help to orient the genetic diagnosis.

Authors/Disclosures
Dina R. Amrom, MD (McGill University) PRESENTER	No disclosure on file
	No disclosure on file
Heli Hunter, NP (Minnesota Center for Multiple Sclerosis)	No disclosure on file
	No disclosure on file
	No disclosure on file
Annapurna Poduri, MD, MD, MPH	An immediate family member of Dr. Poduri has received personal compensation for serving as an employee of Beam Therapeutics. An immediate family member of Dr. Poduri has stock in Beam Therapeutics. The institution of Dr. Poduri has received research support from NIH.
	No disclosure on file
	No disclosure on file
Vijay Ganesh, MD (Brigham and Women's Hospital)	Dr. Ganesh has received personal compensation in the range of $500-$4,999 for serving as a Honorarium with Muscular Dystrophy Association.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Eugen Trinka	Eugen Trinka has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Eugen Trinka has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Eugen Trinka has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bial. Eugen Trinka has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GW Pharmaceuticals. The institution of Eugen Trinka has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Rapport. The institution of Eugen Trinka has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbott. The institution of Eugen Trinka has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Eugen Trinka has received research support from European Union. Eugen Trinka has received publishing royalties from a publication relating to health care.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Francois Dubeau, MD (Montreal Neurological Hospital and Institute)	Dr. Dubeau has nothing to disclose.
	No disclosure on file
	No disclosure on file
William B. Dobyns, MD	No disclosure on file
Frederick Andermann, MD, FRCPC, FAAN	No disclosure on file
Christopher Walsh, MD, PhD (Boston Children'S Hospital)	Dr. Walsh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Maze therapeutics. Dr. Walsh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Third Rock Ventures. Dr. Walsh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Flagship Pioneering. Dr. Walsh has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Annals of Neurology.
Eva Andermann, MD, PhD (Montreal Neurological Inst)	No disclosure on file

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