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Pediatric Annals Aug 2023Miller-Dieker syndrome (MDS) is a rare disease characterized by type I lissencephaly, craniofacial dysmorphisms, intellectual disability, seizures, and death in early... (Review)
Review
Miller-Dieker syndrome (MDS) is a rare disease characterized by type I lissencephaly, craniofacial dysmorphisms, intellectual disability, seizures, and death in early childhood. We report a case of a premature infant with MDS with an anomalous right coronary artery from the pulmonary artery who developed sudden bowel ischemia. This case prompts the reconsideration of cardiovascular involvement in patients with MDS. In addition, this review highlights key clinical features and reviews the critical manifestations of MDS that persist into childhood. .
Topics: Infant; Infant, Newborn; Humans; Child, Preschool; Classical Lissencephalies and Subcortical Band Heterotopias; Abnormalities, Multiple; Pulmonary Artery; Coronary Vessels; Ischemia
PubMed: 37561828
DOI: 10.3928/19382359-20230613-02 -
Ultrasound in Obstetrics & Gynecology :... Feb 2024Microcephaly with simplified gyral pattern (MSG) is an intrinsic genetic central nervous system disorder, characterized by microcephaly (a reduction of brain volume) and...
Microcephaly with simplified gyral pattern (MSG) is an intrinsic genetic central nervous system disorder, characterized by microcephaly (a reduction of brain volume) and a simplified gyral pattern (a reduced number of gyri and shallow sulci associated with normal cortical thickness and neuroanatomical architecture), related to a reduced number of neuronal progenitors in the germinal matrix. We report the first prenatal series of MSG and define the prenatal imaging pattern, which should inform diagnosis and guide prenatal counseling in cases of fetal microcephaly. In this single-center retrospective study of fetuses with MSG, we assessed features on ultrasound and magnetic resonance imaging (MRI), as well as genetic and neuropathological/postnatal data. We included eight patients who had been referred following observation of microcephaly. Ultrasound examination confirmed microcephaly, with a mean growth delay in head circumference of 3.4 weeks, associated with both a lack of gyration and a lack of opercularization of the Sylvian fissure and without any extracephalic anomaly. Fetal brain MRI confirmed lack of gyration with normal cortical thickness and normal intensity of the white matter in all cases. These MRI features led to exclusion of migration/corticogenesis disorders (lissencephaly/polymicrogyria), instead suggesting MSG. The posterior fossa was normal in seven of the eight cases. The corpus callosum was thin in four cases, hypoplastic in two and dysgenetic in two. In four cases, the pregnancy was terminated. The diagnosis of MSG was confirmed from neuropathological and postnatal MRI data. MSG was associated with a genetic diagnosis of RTTN (n = 1) and ASPM (n = 2) biallelic variants in three of the six cases in which genetic work-up was performed. Mild or moderate intellectual deficit with speech delay was present in the three surviving children who were at least 5 years of age at their last examination, without seizures. In conclusion, in the presence of isolated fetal microcephaly with lack of gyration on ultrasound, fetal cerebral MRI is key to diagnosing MSG, which, in the majority of cases, affects the supratentorial space exclusively, and to ruling out other cortical malformations that show a similar sonographic pattern. In addition to imaging, genetic assessment may guide prenatal counseling, since the prenatal prognosis of MSG is different from that of both diffuse polymicrogyria and lissencephaly. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Child; Female; Pregnancy; Humans; Microcephaly; Retrospective Studies; Polymicrogyria; Prenatal Diagnosis; Nervous System Malformations; Magnetic Resonance Imaging; Lissencephaly; Ultrasonography, Prenatal
PubMed: 37551048
DOI: 10.1002/uog.27450 -
Journal of Clinical Neuroscience :... Sep 2023
Topics: Humans; White Matter; Classical Lissencephalies and Subcortical Band Heterotopias; Cerebral Cortex; Diffusion Tensor Imaging; Brain
PubMed: 37549436
DOI: 10.1016/j.jocn.2023.08.003 -
Genes Jun 202317p13 is a chromosomal region characterized by genomic instability due to high gene density leading to multiple deletion and duplication events. 17p13.3 microduplication...
17p13 is a chromosomal region characterized by genomic instability due to high gene density leading to multiple deletion and duplication events. 17p13.3 microduplication syndrome is a rare condition, reported only in 40 cases worldwide, which is found in the Miller-Dieker chromosomal region, presenting a wide range of phenotypic manifestations. Usually, the duplicated area is de novo and varies in size from 1.8 to 4.0 Mbp. Critical genes for this region are (#601545), (#605066), and (#164762). 17p13.3 microduplication syndrome can be categorized into two classes (Class I and Class II) based on the genes that are present in the duplicated area, which lead to different phenotypes. In this report, we present a new case of Class I 17p13.3 microduplication syndrome that presents with unilateral sensorineural hearing loss. Oligonucleotide and SNP array comparative genomic hybridization (a-CGH) analysis revealed a duplication of approximately 121 Kbp on chromosome 17p13.3, which includes and genes. Whole-exome sequencing (WES) analysis confirmed the duplication. Our patient has common clinical symptoms of Class I 17p13.3 microduplication syndrome, and in addition, she has unilateral sensorineural hearing loss. Interestingly, WES analysis did not detect any mutations in genes that are associated with hearing loss. The above findings lead us to propose that hearing loss is a manifestation of 17p13.3 duplication syndrome.
Topics: Female; Humans; Hearing Loss, Unilateral; Comparative Genomic Hybridization; Classical Lissencephalies and Subcortical Band Heterotopias; Chromosome Duplication; Chromosome Disorders; Chromosome Deletion; Hearing Loss, Sensorineural
PubMed: 37510238
DOI: 10.3390/genes14071333 -
Journal of Pediatric Ophthalmology and... 2023A 2-year-old girl with severe muscular dystrophy presented with unilateral eye pain and corneal clouding. She was found to have absent red reflex, hypotonia, cerebral...
A 2-year-old girl with severe muscular dystrophy presented with unilateral eye pain and corneal clouding. She was found to have absent red reflex, hypotonia, cerebral hypoplasia, and iris bombe on ultrasound biomicroscopy, a feature not previously reported in this syndrome. She responded favorably to surgical management. Iris bombe can be a cause of glaucoma in muscle-eye-brain disease. This highlights the importance of incorporating ultrasound biomicroscopy into the diagnostic algorithm of muscle-eye-brain disease and other types of congenital syndromic glaucoma. .
Topics: Female; Humans; Child, Preschool; Iris; Walker-Warburg Syndrome; Iris Diseases; Glaucoma; Microscopy, Acoustic
PubMed: 37478202
DOI: 10.3928/01913913-20230518-01 -
American Journal of Medical Genetics.... Oct 2023Biallelic pathogenic variants in LAMB1 have been associated with autosomal recessive lissencephaly 5 (OMIM 615191), which is characterized by brain malformations...
Biallelic pathogenic variants in LAMB1 have been associated with autosomal recessive lissencephaly 5 (OMIM 615191), which is characterized by brain malformations (cobblestone lissencephaly, hydrocephalus), developmental delay, and epilepsy. Pathogenic variants in LAMB1 are rare, with only 11 pathogenic variants and 11 patients reported to date. Here, we report on a 6-year-old patient from a consanguineous family with profound developmental delay, microcephaly, and a history of a perinatal cerebrovascular event. Brain magnetic resonance imaging (MRI) showed cerebellar cystic defects, signal intensity abnormalities, and a hypoplastic corpus callosum. Trio-exome analysis revealed a homozygous in-frame deletion of Exons 23 and 24 of LAMB1 affecting 104 amino acids including the epidermal growth factor (EGF)-like units 11 and 12 in Domain III. To our knowledge, this is the first reported in-frame deletion in LAMB1. Our findings broaden the clinical and molecular spectrum of LAMB1-associated syndromes.
Topics: Pregnancy; Female; Humans; Child; Nervous System Malformations; Brain; Microcephaly; Sequence Deletion; Homozygote; Laminin
PubMed: 37466007
DOI: 10.1002/ajmg.a.63349 -
Frontiers in Cellular Neuroscience 2023Microtubules are dynamic cytoskeletal structures involved in several cellular functions, such as intracellular trafficking, cell division and motility. More than other...
Microtubules are dynamic cytoskeletal structures involved in several cellular functions, such as intracellular trafficking, cell division and motility. More than other cell types, neurons rely on the proper functioning of microtubules to conduct their activities and achieve complex morphologies. Pathogenic variants in genes encoding for α and β-tubulins, the structural subunits of microtubules, give rise to a wide class of neurological disorders collectively known as "tubulinopathies" and mainly involving a wide and overlapping range of brain malformations resulting from defective neuronal proliferation, migration, differentiation and axon guidance. Although tubulin mutations have been classically linked to neurodevelopmental defects, growing evidence demonstrates that perturbations of tubulin functions and activities may also drive neurodegeneration. In this study, we causally link the previously unreported missense mutation p.I384N in TUBA1A, one of the neuron-specific α-tubulin isotype I, to a neurodegenerative disorder characterized by progressive spastic paraplegia and ataxia. We demonstrate that, in contrast to the p.R402H substitution, which is one of the most recurrent TUBA1A pathogenic variants associated to lissencephaly, the present mutation impairs TUBA1A stability, reducing the abundance of TUBA1A available in the cell and preventing its incorporation into microtubules. We also show that the isoleucine at position 384 is an amino acid residue, which is critical for α-tubulin stability, since the introduction of the p.I384N substitution in three different tubulin paralogs reduces their protein level and assembly into microtubules, increasing their propensity to aggregation. Moreover, we demonstrate that the inhibition of the proteasome degradative systems increases the protein levels of TUBA1A mutant, promoting the formation of tubulin aggregates that, as their size increases, coalesce into inclusions that precipitate within the insoluble cellular fraction. Overall, our data describe a novel pathogenic effect of p.I384N mutation that differs from the previously described substitutions in , and expand both phenotypic and mutational spectrum related to this gene.
PubMed: 37435044
DOI: 10.3389/fncel.2023.1162363 -
Zhonghua Yi Xue Yi Chuan Xue Za Zhi =... Jul 2023To explore the genetic basis for a Chinese pedigree affected with recurrent fetal hydrocephalus.
OBJECTIVE
To explore the genetic basis for a Chinese pedigree affected with recurrent fetal hydrocephalus.
METHODS
A couple who had presented at the Affiliated Hospital of Putian College on March 3, 2021 was selected as the study subject. Following elective abortion, fetal tissue and peripheral blood samples were respectively obtained from the abortus and the couple, and were subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing.
RESULTS
The fetus was found to harbor compound heterozygous variants of the B3GALNT2 gene, namely c.261-2A>G and c.536T>C (p.Leu179Pro), which were inherited from its father and mother, respectively.According to the guidelines of American College of Medical Genetics and Genomics, both variants were classified as pathogenic (PVS1+PM2_Supporting; PM3+PM2_Supporting+PP3+PP4).
CONCLUSION
The compound heterozygous variants of the B3GALNT2 gene probably underlay the α-dystroglycanopathy in this fetus. Above results have provided a basis for genetic counseling of this pedigree.
Topics: Female; Humans; Pregnancy; Aborted Fetus; Asian People; East Asian People; Fetus; Genetic Counseling; Mutation; N-Acetylgalactosaminyltransferases; Pedigree; Walker-Warburg Syndrome
PubMed: 37368380
DOI: 10.3760/cma.j.cn511374-20220624-00426 -
Journal of Neuroimaging : Official... 2023Subcortical band heterotopia (SBH) is a malformation of cortical development diagnosed via MRI. Currently, patients with SBH are classified according to Di Donato's...
BACKGROUND AND PURPOSE
Subcortical band heterotopia (SBH) is a malformation of cortical development diagnosed via MRI. Currently, patients with SBH are classified according to Di Donato's classification. We aimed to show a variation of SBH and the usefulness of double inversion recovery (DIR) images.
METHODS
We retrospectively reviewed the MRI findings of 28 patients with SBH. The patients were classified according to Donato's classification by using conventional MR images, and their DIR findings were reviewed.
RESULTS
Of 28 patients, 20 were grade 1 and 8 were grade 2 according to Di Donato's classification. In 15 of 28 patients, the following four types of atypical MRI findings were detected: asymmetry distribution (four cases), coexistence of thin and thick SBH (five cases), and DIR faint abnormal signal intensity in subcortical white matter (five cases) and in deep white matter (five cases). The latter two types were detected on DIR alone and have not been reported. Additionally, these were identified only in the mild group (Di Donato's classification 1-1 or 1-2).
CONCLUSION
DIR is a useful MRI sequence for detecting faint white matter signal abnormalities, and it can aid in the accurate classification of SBH and identification of its variations, which may reflect the pathology of SBH.
Topics: Humans; Classical Lissencephalies and Subcortical Band Heterotopias; Retrospective Studies; Magnetic Resonance Imaging
PubMed: 37355835
DOI: 10.1111/jon.13141