-
Brain & Development Mar 2021Pallister-Killian syndrome (PKS) is a rare disorder caused by the mosaic tetrasomy of chromosome 12p, and is characterized by facial dysmorphism, developmental delay,...
BACKGROUND
Pallister-Killian syndrome (PKS) is a rare disorder caused by the mosaic tetrasomy of chromosome 12p, and is characterized by facial dysmorphism, developmental delay, hypotonia and seizures.
RESULTS
We report a patient with PKS showing unique polymicrogyria with calcification. He had delayed development and dysmorphic facial features including frontal bossing, hypertelorism, and high arched palate at 6 months of age. Neuroimaging revealed unilateral polymicrogyria with spot calcifications, which predominantly affected the right perisylvian region. Chromosome G-banding showed the karyotype 46,XY, however, array-based comparative genomic hybridization analysis showed mosaic duplication of chromosome 12p, in which CCND2, which encodes cyclin D2 and is a downstream mediator of PI3K-AKT pathway, is located. Supernumerary chromosome of 12p was detected in 58% of buccal mucosa cells by the interphase fluorescence in situ hybridization analysis using chromosome 12 centromere-specific D12Z3 probe. The diagnosis of PKS was made based on distinctive clinical features of our patient and the results of cytogenetic analyses.
CONCLUSION
This report is, to our knowledge, the first case of a patient with PKS who clearly demonstrates polymicrogyria colocalized with calcifications, as shown by CT scans and MRI, and suggests that a patient with PKS could show structural brain anomalies with calcification. We assume that somatic mosaicism of tetrasomy could cause asymmetrical polymicrogyria in our patient, and speculate that increased dosages of CCND2 at chromosome 12p might be involved in the abnormal neuronal migration in PKS.
Topics: Brain Diseases; Calcinosis; Chromosome Disorders; Chromosomes, Human, Pair 12; Comparative Genomic Hybridization; Humans; Infant; Male; Microarray Analysis; Polymicrogyria
PubMed: 33229101
DOI: 10.1016/j.braindev.2020.11.003 -
Ryoikibetsu Shokogun Shirizu 2000
-
The Neuroradiology Journal Oct 2014SUMMARY - We describe a child from consanguineous parents presenting mega corpus callosum (MegaCC), polymicrogyria, psychomotor retardation with swallowing difficulties... (Review)
Review
SUMMARY - We describe a child from consanguineous parents presenting mega corpus callosum (MegaCC), polymicrogyria, psychomotor retardation with swallowing difficulties and language impairment perhaps linked to the syndrome of megalencephaly-polymicrogyria-mega corpus callosum (MEG-PMG-MegaCC). Reviewing the literature, we speculate that MegaCC, psychomotor retardation and anomalies in cortical migration are the three pathognomonic features. The presence of additional possibly associated anomalies such as megalencephaly, indicates that the spectrum of linked malformations with this rare syndrome is broad and yet to be defined.
Topics: Brain; Child, Preschool; Corpus Callosum; Deglutition Disorders; Female; Humans; Language Disorders; Magnetic Resonance Imaging; Megalencephaly; Polymicrogyria; Syndrome
PubMed: 25260206
DOI: 10.15274/NRJ-2014-10065 -
Epilepsia Open Mar 2023Bilateral frontoparietal polymicrogyria (BFPP) is a rare genetic-related migration disorder. It has been attributed to loss-of-function of the ADGRG1 gene, which encodes... (Review)
Review
Identification and clinical characteristics of a novel missense ADGRG1 variant in bilateral Frontoparietal Polymicrogyria: The electroclinical change from infancy to adulthood after Callosotomy in three siblings.
OBJECTIVE
Bilateral frontoparietal polymicrogyria (BFPP) is a rare genetic-related migration disorder. It has been attributed to loss-of-function of the ADGRG1 gene, which encodes an adhesion G protein-coupled receptor, ADGRG1/GPR56. We report the EEG findings of BFPP in three Asian patients, and confirmed that change in protein function was caused by the novel missense variant (p.Leu290Pro).
METHODS
We reviewed the medical records of three siblings with BFPP including one elder girl and two identical twin boys from birth to adulthood. The clinical symptoms, electroencephalography (EEG), brain MRI, whole-exome sequencing, treatment including medications, neuromodulation, and epilepsy surgery, and clinical outcomes were reviewed. The protein structure of a novel missense variant (p.Leu290Pro) was predicted by in silico studies, and molecular analysis was performed via typical flow cytometry and Western blotting.
RESULTS
The elder girl (Patient 1) was 22 years old and the twin boys (Patients 2 and 3) were 20 years old at the time of publication. All of them presented with typical clinical symptoms/signs and MRI findings of BFPP. Whole-exome sequencing followed by Sanger confirmation showed that all three patients had compound heterozygous variants in the ADGRG1 gene. The missense variant (p.Leu290Pro) was confirmed to be related to a reduction in cell surface GPR56 expression. High-amplitude rhythmic activity was noted in sleep EEG during infancy, which may have been due to excessive sleep spindle, and the rhythm disappeared when they were of pre-school age. Partial callosotomy provided short-term benefits in seizure control in Patients 1 and 2, and combined vagus nerve stimulation and partial callosotomy provided longer benefits in Patient 3.
SIGNIFICANCE
Sleep EEG findings of high-amplitude rhythmic activity in our BFPP cases were only noted during infancy and childhood. We also confirmed that the missense variant (p.Leu290Pro) led to loss of function due to a reduction in cell surface GPR56 expression.
Topics: Male; Female; Humans; Infant; Child, Preschool; Child; Young Adult; Adult; Polymicrogyria; Siblings; Receptors, G-Protein-Coupled; Mutation, Missense
PubMed: 36524291
DOI: 10.1002/epi4.12685 -
Clinical Genetics Feb 2014Dominant mutations in TUBB2B have been reported in patients with polymicrogyria. We further explore the phenotype associated with mutations in TUBB2B. Twenty patients...
Dominant mutations in TUBB2B have been reported in patients with polymicrogyria. We further explore the phenotype associated with mutations in TUBB2B. Twenty patients with polymicrogyria (five unilateral) were tested for mutations in TUBB2B by Sanger sequencing. We identified two novel de novo mutations, c.743C>T (p.Ala248Val) and c.1139G>T (p.Arg380Leu) in exon 4 of TUBB2B in three unrelated families. Brain magnetic resonance images showed polymicrogyria involving predominantly the perisylvian regions. In addition, there was a dysmorphic appearance of the basal ganglia, thin corpus callosum, enlargement of the ventricles, thinning of the white matter and hypoplasia of pons and cerebellar vermis. This combination of associated features was absent in all 17 patients with polymicrogyria in whom no mutation was identified. This report underlines that the association of polymicrogyria with thin or absent corpus callosum, dysmorphic basal ganglia, brainstem and vermis hypoplasia is highly likely to result from mutations in TUBB2B and provides further insight in how mutations in TUBB2B affect protein function.
Topics: Basal Ganglia; Base Sequence; DNA Mutational Analysis; Dyneins; Genes, Dominant; Humans; Magnetic Resonance Imaging; Models, Molecular; Molecular Sequence Data; Phenotype; Polymicrogyria; Tubulin
PubMed: 23495813
DOI: 10.1111/cge.12141 -
Frontiers in Pediatrics 2021Pathogenic variants of the gene are associated with bilateral frontoparietal polymicrogyria, defined radiologically by polymicrogyria with an anterior-posterior...
Pathogenic variants of the gene are associated with bilateral frontoparietal polymicrogyria, defined radiologically by polymicrogyria with an anterior-posterior gradient, pontine and cerebellar hypoplasia and patchy white matter abnormalities. We report a novel homozygous variant with atypical features. The patient presented at 8 months of age with motor delay, esotropia, hypotonia with hyporeflexia and subsequently developed refractory epilepsy. At the last assessment, aged 12 years, head control, sitting and language were not acquired. Magnetic resonance imaging revealed diffuse polymicrogyria with relative sparing of the anterior temporal lobes, without an anterior-posterior gradient, diffuse hypomyelination and pontine and cerebellar hypoplasia. A panel targeting brain morphogenesis defects yielded an unreported homozygous nonsense variant (dbSNP rs746634404), present in the heterozygous state in both parents. We report a novel variant associated with diffuse polymicrogyria without an identifiable anterior-posterior gradient, diffuse hypomyelination and a severe motor and cognitive phenotype. Our case highlights the phenotypic diversity of pathogenic variants and the clinico-anatomical overlap between recognized polymicrogyria syndromes.
PubMed: 34513772
DOI: 10.3389/fped.2021.728077 -
AJNR. American Journal of Neuroradiology Feb 1997
Topics: Cerebellum; Humans; Muscular Dystrophies
PubMed: 9111684
DOI: No ID Found -
American Journal of Obstetrics and... Dec 2020Cytomegalovirus infection is the most frequent congenital infection and a major cause of long-term neurologic morbidity. The aim of this meta-analysis was to calculate... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Cytomegalovirus infection is the most frequent congenital infection and a major cause of long-term neurologic morbidity. The aim of this meta-analysis was to calculate the pooled rates of vertical transmission and fetal impairments according to the timing of primary maternal infection.
DATA SOURCES
From inception to January 2020, MEDLINE, Scopus, Cochrane Library, and gray literature sources were used to search for related studies.
STUDY ELIGIBILITY CRITERIA
Cohort and observational studies reporting the timing of maternal cytomegalovirus infections and rate of vertical transmission or fetal impairments were included. The primary outcomes were vertical transmission and fetal insult, defined as either prenatal findings from the central nervous system leading to termination of pregnancy or the presence of neurologic symptoms at birth. The secondary outcomes included sensorineural hearing loss or neurodevelopmental delay at follow-up and prenatal central nervous system ultrasonography findings.
STUDY APPRAISAL AND SYNTHESIS METHODS
The pooled rates of the outcomes of interest with their 95% confidence intervals (CI) were calculated for primary maternal infection at the preconception period, periconception period, first trimester, second trimester, and third trimester.
RESULTS
A total of 17 studies were included. The pooled rates of vertical transmission (10 studies, 2942 fetuses) at the preconception period, periconception period, first trimester, second trimester, and third trimester were 5.5% (95% CI, 0.1-10.8), 21.0% (95% CI, 8.4-33.6), 36.8% (95% CI, 31.9-41.6), 40.3% (95% CI, 35.5-45.1), and 66.2% (95% CI, 58.2-74.1), respectively. The pooled rates of fetal insult in case of transmission (10 studies, 796 fetuses) were 28.8% (95% CI, 2.4-55.1), 19.3% (95% CI, 12.2-26.4), 0.9% (95% CI, 0-2.4%), and 0.4% (95% CI, 0-1.5), for maternal infection at the periconception period, first trimester, second trimester, and third trimester, respectively. The pooled rates of sensorineural hearing loss for maternal infection at the first, second, and third trimester were 22.8% (95% CI, 15.4-30.2), 0.1% (95% CI, 0-0.8), and 0% (95% CI, 0-0.1), respectively.
CONCLUSION
Vertical transmission after maternal primary cytomegalovirus infection increases with advancing pregnancy, starting from the preconception period. However, severe fetal impairments are rare after infection in the first trimester of pregnancy.
Topics: Abortion, Induced; Cytomegalovirus Infections; Female; Gestational Age; Hearing Loss, Sensorineural; Humans; Infectious Disease Transmission, Vertical; Microcephaly; Nervous System Malformations; Neurodevelopmental Disorders; Polymicrogyria; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, First; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Time Factors
PubMed: 32460972
DOI: 10.1016/j.ajog.2020.05.038 -
Revista de Neurologia
Topics: Brain; Child, Preschool; Humans; Male
PubMed: 17033986
DOI: No ID Found -
Cureus May 2022Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) is an uncommon malformation syndrome, characterized by primary megalencephaly, capillary...
Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) is an uncommon malformation syndrome, characterized by primary megalencephaly, capillary malformations of the midline face and body, or distal limb anomalies such as syndactyly and polymicrogyria. Herein, we report a young male child, who presented with complaints of increasing head size, delay in speech, and one episode of focal seizure with distinctive morphological and neuroradiological manifestations which led to the diagnosis of MCAP. We have also reviewed recently published literature and the various diagnostic criteria proposed by authors to achieve the early clinical diagnosis of these patients in the outpatient department.
PubMed: 35733479
DOI: 10.7759/cureus.25123