Genetic causes underlying grey matter heterotopia

Vriend, Ilona; Oegema, Renske

doi:10.1016/j.ejpn.2021.09.015

Cited by 29 publications

(18 citation statements)

References 119 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Epilepsy was found in 72% of patients with PNH, with a mean age of 12 years 6) . PNH may also show some cen tral nervous system anomalies, including corpus callosum agenesis, hydrocephalus, or lissencephaly, and cardiovascular abnorma lities, such as aortic valve insufficiency or PDA 7) . This patient had symptomatic PDA that had to be ligated surgically; however, she did not show any signs of PNH during antenatal care.…”

Section: Discussionmentioning

confidence: 99%

“…The main differential diagnosis for PNH is tuberous sclerosis, which can involve subependymal tubers; however, these can be differentiated because lesions in tuberous sclerosis are often calcified, irregular in shape, and enhanced after gadolinium administration 9) . PNH can be found in isolated gene defects; however, it seems to be a genetically heterogeneous disease involving many different genes, such as FLNA, ARFGEF2, neural precursor cell ex pressed, developmentally downregulated 4-like (NEDD4L), and microtubule-associated protein 1 B (MAP1B) 7) . Additionally, PNH is associated with many syndromes, including Ehlers-Danlos, Fragile X, and Williams syndrome 1,7) .…”

Section: The Patient Had Recurrent Apnea and Longstanding Cyanosismentioning

confidence: 99%

“…PNH can be found in isolated gene defects; however, it seems to be a genetically heterogeneous disease involving many different genes, such as FLNA, ARFGEF2, neural precursor cell ex pressed, developmentally downregulated 4-like (NEDD4L), and microtubule-associated protein 1 B (MAP1B) 7) . Additionally, PNH is associated with many syndromes, including Ehlers-Danlos, Fragile X, and Williams syndrome 1,7) . FLNA-related X-linked PNH shows rather specific bilateral heterotopia in combination with cerebellar hypoplasia and corpus callosum abnormalities 10) .…”

Section: The Patient Had Recurrent Apnea and Longstanding Cyanosismentioning

confidence: 99%

See 2 more Smart Citations

Newborn Periventricular Nodular Heterotopia with Persistent Feeding Cyanosis and Apneic Spell: A Case Report

et al. 2022

View full text Add to dashboard Cite

Periventricular nodular heterotopia (PNH) is a neuronal migration disorder that occurs during early brain development. Patients with PNH may be asymptomatic and have normal intelligence; however, PNH is also known to cause various symptoms such as seizures, dyslexia, and cardiovascular anomalies. PNH is not commonly diagnosed during early infancy because of the lack of clinical manifestations during this period. We present the case of a female infant diagnosed with PNH based on brain magnetic resonance imaging, who had symptomatic patent ductus arteriosus that had to be ligated surgically and had prolonged feeding cyanosis with frequent apneic spells.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: The Patient Had Recurrent Apnea and Longstanding Cyanosismentioning

confidence: 99%

Section: The Patient Had Recurrent Apnea and Longstanding Cyanosismentioning

confidence: 99%

See 1 more Smart Citation

Newborn Periventricular Nodular Heterotopia with Persistent Feeding Cyanosis and Apneic Spell: A Case Report

et al. 2022

View full text Add to dashboard Cite

show abstract

“…We broadened neuronal migration to include axon guidance and growth cone formation because many axon guidance molecules are pleiotropic, with diverse functions in multiple tissues and in the brain, including neuronal migration in the developing brain [ 82 , 83 ] and growth cones are at the tips of the leading processes of migrating neurons and elongating axons [ 82 , 83 ]. Genes in all three pathways have been implicated in disorders of neuronal migration, including periventricular nodular heterotopia [ 84 ], a neuronal migration disorder in which cortical development is compromised, leading to epilepsy and RD [ 85 ]. A total of ~115,000 variants in 351 genes were tested (Table S2 ).…”

Section: Methodsmentioning

confidence: 99%

Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities

et al. 2022

View full text Add to dashboard Cite

Reading Disability (RD) is often characterized by difficulties in the phonology of the language. While the molecular mechanisms underlying it are largely undetermined, loci are being revealed by genome-wide association studies (GWAS). In a previous GWAS for word reading (Price, 2020), we observed that top single-nucleotide polymorphisms (SNPs) were located near to or in genes involved in neuronal migration/axon guidance (NM/AG) or loci implicated in autism spectrum disorder (ASD). A prominent theory of RD etiology posits that it involves disturbed neuronal migration, while potential links between RD-ASD have not been extensively investigated. To improve power to identify associated loci, we up-weighted variants involved in NM/AG or ASD, separately, and performed a new Hypothesis-Driven (HD)–GWAS. The approach was applied to a Toronto RD sample and a meta-analysis of the GenLang Consortium. For the Toronto sample (n = 624), no SNPs reached significance; however, by gene-set analysis, the joint contribution of ASD-related genes passed the threshold (p~1.45 × 10–2, threshold = 2.5 × 10–2). For the GenLang Cohort (n = 26,558), SNPs in DOCK7 and CDH4 showed significant association for the NM/AG hypothesis (sFDR q = 1.02 × 10–2). To make the GenLang dataset more similar to Toronto, we repeated the analysis restricting to samples selected for reading/language deficits (n = 4152). In this GenLang selected subset, we found significant association for a locus intergenic between BTG3-C21orf91 for both hypotheses (sFDR q < 9.00 × 10–4). This study contributes candidate loci to the genetics of word reading. Data also suggest that, although different variants may be involved, alleles implicated in ASD risk may be found in the same genes as those implicated in word reading. This finding is limited to the Toronto sample suggesting that ascertainment influences genetic associations.

show abstract

“…PVNH is an infrequent feature of many rare genetic disorders, with a small number manifesting it as a consistent association, as summarized by Vriend and Oegema. 15 The major genetic locus for PVNH is FLNA, with pathogenic variants estimated to account for one-quarter of cases. 16 In addition to PVNH, we observed a previously unrecognized characteristic pattern of additional structural brain anomalies in ZTTK syndrome.…”

mentioning

confidence: 99%

Distinctive Brain Malformations in Zhu-Tokita-Takenouchi-Kim Syndrome

Halliday

Baynam

Ewans

et al. 2022

AJNR Am J Neuroradiol

View full text Add to dashboard Cite

BACKGROUND AND PURPOSE: Zhu-Tokita-Takenouchi-Kim syndrome is a severe multisystem malformation disorder characterized by developmental delay and a diverse array of congenital abnormalities. However, these currently identified phenotypic components provide limited guidance in diagnostic situations, due to both the nonspecificity and variability of these features. Here we report a case series of 7 individuals with a molecular diagnosis of Zhu-Tokita-Takenouchi-Kim syndrome, 5 ascertained by their presentation with the neuronal migration disorder, periventricular nodular heterotopia.MATERIALS AND METHODS: Individuals with a molecular diagnosis of Zhu-Tokita-Takenouchi-Kim syndrome were recruited from 2 sources, a high-throughput sequencing study of individuals with periventricular nodular heterotopia or from clinical diagnostic sequencing studies. We analyzed available brain MR images of recruited individuals to characterize periventricular nodular heterotopia distribution and to identify the presence of any additional brain abnormalities.RESULTS: Pathogenic variants in SON, causative of Zhu-Tokita-Takenouchi-Kim syndrome, were identified in 7 individuals. Brain MR images from these individuals were re-analyzed. A characteristic set of imaging anomalies in addition to periventricular nodular heterotopia was identified, including the elongation of the pituitary stalk, cerebellar enlargement with an abnormally shaped posterior fossa, rounding of the caudate nuclei, hippocampal malformations, and cortical anomalies including polymicrogyria or dysgyria. CONCLUSIONS:The recurrent neuroradiologic changes identified here represent an opportunity to guide diagnostic formulation of Zhu-Tokita-Takenouchi-Kim syndrome on the basis of brain MR imaging evaluation.ABBREVIATIONS: PVNH ¼ periventricular nodular heterotopia; VUS ¼ variant of uncertain significance; WES ¼ whole-exome sequencing; WGS ¼ wholegenome sequencing; ZTTK syndrome ¼ Zhu-Tokita-Takenouchi-Kim syndrome U nderstanding of the distinctive phenotypic features of a rare syndromic disorder facilitates earlier diagnosis. This is particularly evident when genomic sequencing studies yield ambiguous findings, such as variants of uncertain significance (VUSs) in syndromic genes. 1 Moreover, characteristic phenotypic features, or "phenotypic handles," often guide focused investigations. Rare phenotypically heterogeneous disorders present a considerable challenge in this respect due to prior ascertainment biases and limited cohort sizes.Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome (OMIM #617140) is a rare phenotypically heterogeneous disorder characterized by developmental delay and a wide array of congenital multisystem anomalies. Haploinsufficiency of SON, mediated by either truncating variants or whole-gene deletions, has been identified as the underlying cause of ZTTK syndrome. 2-5 SON encodes the RNA-binding protein SON and is constitutively expressed, though expression is enriched during early brain

show abstract

Genetic causes underlying grey matter heterotopia

Cited by 29 publications

References 119 publications

Newborn Periventricular Nodular Heterotopia with Persistent Feeding Cyanosis and Apneic Spell: A Case Report

Newborn Periventricular Nodular Heterotopia with Persistent Feeding Cyanosis and Apneic Spell: A Case Report

Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities

Distinctive Brain Malformations in Zhu-Tokita-Takenouchi-Kim Syndrome

Contact Info

Product

Resources

About