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: 11.91). 05/2003; 53(5):596 - 606. DOI: 10.1002/ana.10520
Source: PubMed

ABSTRACT 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

Download full-text


Available from: Rachel Straussberg, Jul 03, 2015
  • Source
    [Show abstract] [Hide abstract]
    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; DOI:10.1093/cercor/bhs292 · 8.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Animal data demonstrate that the development of distinct cortical areas is influenced by genes that exhibit highly regionalized expression patterns. In this paper, we show genetic patterning of cortical surface area derived from MRI data from 406 adult human twins. We mapped genetic correlations of areal expansion between selected seed regions and all other cortical locations, with the selection of seed points based on results from animal studies. "Marching seeds" and a data-driven, hypothesis-free, fuzzy-clustering approach provided convergent validation. The results reveal strong anterior-to-posterior graded, bilaterally symmetric patterns of regionalization, largely consistent with patterns previously reported in nonhuman mammalian models. Broad similarities in genetic patterning between rodents and humans might suggest a conservation of cortical patterning mechanisms, whereas dissimilarities might reflect the functionalities most essential to each species.
    Neuron 11/2011; 72(4):537-44. DOI:10.1016/j.neuron.2011.08.021 · 15.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The availability of microarray technology has led to the recent recognition of copy number abnormalities of distal chromosome 22q11.2 that are distinct from the better-characterized deletions and duplications of the proximal region. This report describes five unrelated individuals with copy number abnormalities affecting distal chromosome 22q11.2. We report on novel phenotypic features including diaphragmatic hernia and uterine didelphys associated with the distal microdeletion syndrome; and frontomedial polymicrogyria and callosal agenesis associated with the distal microduplication syndrome. We describe the third distal chromosome 22q11.2 microdeletion patient with Goldenhar syndrome. Patients with distal chromosome 22q11.2 copy number abnormalities exhibit inter- and intra-familial phenotypic variability, and challenge our ability to draw meaningful genotype-phenotype correlations.
    American Journal of Medical Genetics Part A 07/2011; 155A(7):1623-33. DOI:10.1002/ajmg.a.34051 · 2.05 Impact Factor