Polymicrogyria, Bilateral Frontoparietal

Alternative Names

  • BFPP
  • Cerebellar Ataxia with Neuronal Migration Defect
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WHO-ICD-10 version:2010

Congenital malformations, deformations and chromosomal abnormalities

Congenital malformations of the nervous system

OMIM Number

606854

Mode of Inheritance

Autosomal recessive

Gene Map Locus

16q13

Description

Polymicrogyria is a common malformation of cortical development that is grossly characterized by abnormal cortical lamination and an excessive number of small gyri. The syndrome is manifested by global developmental delay of at least moderate severity, epilepsy, dysconjugate gaze, and bilateral pyramidal and cerebellar signs. Polymicrogyria can be generalized or focal, unilateral or bilateral. Among the rare, bilateral symmetrical forms several syndromes, such as bilateral frontal, frontoparietal, perisylvian, and parasagittal parieto-occipital polymicrogyria have been recognized. Severity of polymicrogyria is dependant on the location and size of the affected area.

The etiology of polymicrogyria is heterogeneous. The topographic arrangement of the lesions, the frequency of bilateral symmetry, and historical data may suggest a transient intrauterine perfusion failure in many patients. However, abnormal hemodynamic data in the fetal cerebral arteries and infectious or toxic theories fail to explain completely the distribution of all polymicrogyric lesions.

 

Molecular Genetics

Both extrinsic and inherited factors can cause polymicrogyria. Bilateral frontoparietal polymicrogyria can be caused by splice site, frameshift, and missense mutations in the G Protein-Coupled Receptor 56 (GPR56) gene. The GPR56 gene, assigned to the region 16q12.2-q21 on chromosome 16, contains 14 exons covering 15 kb and has a 3-kb open reading frame. GPR56 signaling plays an essential role in regional development of human cerebral cortex.

Epidemiology in the Arab World

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Other Reports

Kuwait

In a large consanguineous Bedouin family, probably from Kuwait, with bilateral frontoparietal polymicrogyria, Piao et al. (2004) identified a C>T transition at nucleotide 1693 of the GPR56 gene, resulting in the substitution of the conserved amino acid (p.R565W). This pedigree consisted of two nuclear families that were distantly related to one another; the two affected individuals from the first family had first-cousin parents, and the affected individual from the second family had consanguineous parents whose exact relationship was unknown. In addition, in one child, born to first cousin Arab parents, with bilateral frontoparietal polymicrogyria, Piao et al. (2004) identified homozygosity for a G>C transversion at nucleotide 272 of exon 3 of the GPR56 gene, resulting in a cysteine-serine substitution at codon 91 (p.C91S).

Palestine

Straussberg et al. (1996) described a Palestinian family in which the parents were first cousins and three of the siblings suffered from moderate mental retardation, pachygyria and strabismus. In 2002, Piao et al. described the clinical and genetic features of the autosomal recessive stereotyped form of polymicrogyria in two consanguineous families from Palestine, includeing the one described by Straussberg et al. (1996)

Chang et al. (2003) reported 19 patients from 10 kindreds with apparent autosomal recessive bilateral frontoparietal polymicrogyria. Included were the 2 families reported previously by Piao et al. (2002).  The authors noted that the syndrome of bilateral frontoparietal polymicrogyria appears to be very common and may be frequently misdiagnosed.

Qatar

In a consanguineous Qatari family with two children with bilateral frontoparietal polymicrogyria, Piao et al. (2004) identified a C>T transition at nucleotide 112 of the GPR56 gene, resulting in an arg-trp substitution at codon 38 (p.R38W) and probably affecting ligand binding by GPR56.

United Arab Emirates

Sztriha and Nork (2000) reported two unrelated Emirati patients with bilateral frontoparietal polymicrogyria born to consanguineous parents. Sztriha and Nork (2002) reported a third case of bilateral symmetrical frontoparietal polymicrogyria in an 8-year-old-boy who was born at term to consanguineous parents of United Arab Emirates origin. 

Sztriha et al. (2004) reported two boys with chromosome 22q11 deletion syndrome and polymicrogyria. Both patients showed severe developmental delay with cardiovascular malformations and one of them had drug resistant epilepsy.  Both patients had serious delay of mental and motor development. They also had dysmorphic features and cardiovascular abnormalities.Histology revealed four-layered polymicrogyria.

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