Bilateral frontoparietal polymicrogyria: Clinical and radiological features in 10 families with linkage to chromosome 16

Comprehensive Epilepsy Center, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, MA
Annals of Neurology (Impact Factor: 9.98). 05/2003; 53(5):596 - 606. DOI: 10.1002/ana.10520
Source: PubMed


Polymicrogyria is a common malformation of cortical development characterized by an excessive number of small gyri and abnormal cortical lamination. Multiple syndromes of region-specific bilateral symmetric polymicrogyria have been reported. We previously have described two families with bilateral frontoparietal polymicrogyria (BFPP), an autosomal recessive syndrome that we mapped to a locus on chromosome 16q12-21. Here, we extend our observations to include 19 patients from 10 kindreds, all linked to the chromosome 16q locus, allowing us to define the clinical and radiological features of BFPP in detail. The syndrome is characterized by global developmental delay of at least moderate severity, seizures, dysconjugate gaze, and bilateral pyramidal and cerebellar signs. Magnetic resonance imaging demonstrated symmetric polymicrogyria affecting the frontoparietal regions most severely, as well as ventriculomegaly, bilateral white matter signal changes, and small brainstem and cerebellar structures. We have refined our genetic mapping and describe two apparent founder haplotypes, one of which is present in two families with BFPP and associated microcephaly. Because 11 of our patients initially were classified as having other malformations, the syndrome of BFPP appears to be more common than previously recognized and may be frequently misdiagnosed. Ann Neurol 2003

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    • "The molecular basis of polymicrogyria is beginning to be elucidated with the identification of a gene GPR56 and its mechanism responsible for bilateral fronto-parietal polymicrogyria.[4] Chromosome 16q12-21 has also been linked to bilateral fronto-parietal polymicrogyria.[56] "
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    ABSTRACT: Polymicrogyria is a type of cortical dysplasia with cortical organizational defect. Bilateral polymicrogyria are distinct with genetic basis in a subset. We hereby report a case of bilateral frontal polymicrogyria (BFP) in association with chorioretinal dystrophy and ectopia lentis (EL) in a 26-year-old lady born of a consanguineous parentage. Her male sibling also had chorioretinal dystrophy and EL. This combination of autosomal recessive inheritance has not been reported earlier in the literature and suggests a role of connective tissue genes in BFP.
    Annals of Indian Academy of Neurology 10/2013; 16(4):678-80. DOI:10.4103/0972-2327.120473 · 0.60 Impact Factor
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    • "Polymicrogyria (PMG) is a malformation of cortical development in which the process of normal cortical development is interrupted during the late stages of neuronal migration; the result is the formation of multiple small gyri and abnormal cortical lamination (Barkovich 2010). Patterns of cortical involvement have been classified and described according to the distribution of the PMG including bilateral frontal (Guerrini et al. 2000), bilateral frontoparietal (Piao et al. 2002; Chang et al. 2003), bilateral perisylvian (Kuzniecky et al. 1993), bilateral parieto-occipital (Guerrini et al. 1997), generalized PMG (Chang et al. 2004), and also unilateral PMG (Chang et al. 2006). A recent study determined the relative frequencies of different PMG patterns with 328 patients and defined the spectrum of their imaging features (Leventer et al. 2010). "
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    ABSTRACT: Polymicrogyria (PMG) is a malformation of cortical development characterized by an irregular gyral pattern and its diagnosis and severity have been qualitatively judged by visual inspection of imaging features. We aimed to provide a quantitative description of abnormal sulcal patterns for individual PMG brains using our sulcal graph-based analysis and examined the association with language impairment. The sulcal graphs were constructed from magnetic resonance images in 26 typical developing and 18 PMG subjects and the similarity between sulcal graphs was computed by using their geometric and topological features. The similarities between typical and PMG groups were significantly lower than the similarities measured within the typical group. Furthermore, more lobar regions were determined to be abnormal in most patients when compared with the visual diagnosis of PMG involvement, suggesting that PMG may have more global effects on cortical folding than previously expected. Among the PMG, the group with intact language development showed sulcal patterns more closely matched with the typical than the impaired group in the left parietal lobe. Our approach shows the potential to provide a quantitative means for detecting the severity and extent of involvement of cortical malformation and a greater understanding of genotype-phenotype and clinical-imaging features correlations.
    Cerebral Cortex 09/2012; 23(12). DOI:10.1093/cercor/bhs292 · 8.67 Impact Factor
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    • "GPR56 is a member of the adhesion G protein-coupled receptor (GPCR) family. Mutations in GPR56 cause a specific human brain malformation called bilateral frontoparietal polymicrogyria (BFPP) [3]–[6]. The magnetic resonance images of BFPP brains revealed a thickened cerebral cortex with coarse gyri, shallow sulci, and a “scalloped” appearance at the grey-white matter junction – much like the radiological features of other polymicrogyria malformations. "
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    ABSTRACT: It has recently been discovered that Collagen III, the encoded protein of the type IV Ehlers-Danlos Syndrome (EDS) gene, is one of the major constituents of the pial basement membrane (BM) and serves as the ligand for GPR56. Mutations in GPR56 cause a severe human brain malformation called bilateral frontoparietal polymicrogyria, in which neurons transmigrate through the BM causing severe mental retardation and frequent seizures. To further characterize the brain phenotype of Col3a1 knockout mice, we performed a detailed histological analysis. We observed a cobblestone-like cortical malformation, with BM breakdown and marginal zone heterotopias in Col3a1⁻/⁻ mouse brains. Surprisingly, the pial BM appeared intact at early stages of development but starting as early as embryonic day (E) 11.5, prominent BM defects were observed and accompanied by neuronal overmigration. Although collagen III is expressed in meningeal fibroblasts (MFs), Col3a1⁻/⁻ MFs present no obvious defects. Furthermore, the expression and posttranslational modification of α-dystroglycan was undisturbed in Col3a1⁻/⁻ mice. Based on the previous finding that mutations in COL3A1 cause type IV EDS, our study indicates a possible common pathological pathway linking connective tissue diseases and brain malformations.
    PLoS ONE 01/2012; 7(1):e29767. DOI:10.1371/journal.pone.0029767 · 3.23 Impact Factor
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