De novo microdeletion of 5q14.3 excludingMEF2Cin a patient with infantile spasms, microcephaly, and agenesis of the corpus callosum

The Aicardi syndrome consists of infantile spasms, defects of the corpus callosum, dorsal vertebral anomalies, and chorioretinal lacunar defects. The etiology is, as yet, unknown. The most likely cause, however, is an χ-linked mutational event that is lethal in males. The first case of the Aicardi syndrome known to occur in one twin is reported. The patient was female and her unaffected sibling was male. This provides strong evidence to support the theory of an χ-linked mutational event as the cause of this condition. The typical chorioretinal defects, often difficult to document because these children die at an early age, are clearly illustrated in this report.

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A Case With 4 de Novo Copy Number Variations With Clinical Features That Overlap 1q43q44 Microdeletion and 3q29 Microduplication Syndromes

Child Neurology Open ◽

10.1177/2329048x18798200 ◽

2018 ◽

Vol 5 ◽

pp. 2329048X1879820

Author(s):

Miriam Kessi ◽

Jing Peng ◽

Lifen Yang ◽

Haolin Duan ◽

Yulin Tang ◽

...

Keyword(s):

Intellectual Disability ◽

Corpus Callosum ◽

Copy Number ◽

De Novo ◽

Copy Number Variations ◽

Language Delay ◽

Global Developmental Delay ◽

Recurrent Infections ◽

Dental Anomalies ◽

Microdeletion Syndrome

1q43q44 microdeletion syndrome is characterized by intellectual disability/global developmental delay, epilepsy, dysmorphic facies, stereotypic movement, language delay, recurrent infections, dental anomalies, and hand and foot anomalies. Microcephaly and corpus callosum dysplasia are present in some cases depending on gene content. 3q29 microduplication syndrome is characterized by intellectual disability, language delay, microcephaly, and dental anomalies. We report the first case with 4 de novo copy number variations with clinical features which overlap 1q43q44 microdeletion and 3q29 microduplication syndromes. Our case presented with global developmental delay, epilepsy, recurrent infections, stereotypic movements, speech delay, microcephaly, facial dysmorphism, bilateral clinodactyly, and small puffy feet with metatarsus varus; however, she had no corpus callosum dysplasia. Our case highlights the role of multiple copy number variations in the occurrence of a certain phenotype. Moreover, it supports the theory that the loss of HNRNPU gene function cannot explain the occurrence of microcephaly and abnormalities of the corpus callosum in 1q43q44 microdeletion syndrome.

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An Unusual Case of Infantile Spasms Due to a Pathogenic Variant in the MECP2 Gene

Journal of Pediatric Neurology ◽

10.1055/s-0039-1683436 ◽

2019 ◽

Vol 18 (01) ◽

pp. 039-044

Author(s):

Behshad Charkhand ◽

Natarie Liu ◽

Karlene T. Barrett ◽

Walla Al-Hertani ◽

Morris H. Scantlebury

Keyword(s):

Unusual Case ◽

De Novo ◽

Epileptic Encephalopathy ◽

Infantile Spasms ◽

Mecp2 Gene ◽

Disease Etiology ◽

Epileptic Spasms ◽

Uncertain Significance ◽

Atypical Presentations ◽

De Novo Variant

AbstractThe infantile spasms (IS) syndrome is a developmental epileptic encephalopathy disorder characterized by epileptic spasms occurring in infancy, hypsarrhythmia on the electroencephalography (EEG) and developmental arrest or regression. The etiologies include structural, metabolic, and genetic causes. We report an unusual case of IS due to a de novo variant in the MECP2 gene. The patient also had variants of uncertain significance in the SCN9A and SCN5A genes inherited from the father and mother, respectively. This report highlights the need for broad genetic testing in MECP2-related disorders with atypical presentations to better understand the disease etiology.

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De Novo Pathogenic Variants in N-cadherin Cause a Syndromic Neurodevelopmental Disorder with Corpus Callosum, Axon, Cardiac, Ocular, and Genital Defects

The American Journal of Human Genetics ◽

10.1016/j.ajhg.2019.09.005 ◽

2019 ◽

Vol 105 (4) ◽

pp. 854-868 ◽

Cited By ~ 3

Author(s):

Andrea Accogli ◽

Sara Calabretta ◽

Judith St-Onge ◽

Nassima Boudrahem-Addour ◽

Alexandre Dionne-Laporte ◽

...

Keyword(s):

Corpus Callosum ◽

De Novo ◽

Neurodevelopmental Disorder ◽

Pathogenic Variants

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Overnight polygraphic study of agenesis of the corpus callosum with seizures resembling infantile spasms

Brain and Development ◽

10.1016/s0387-7604(80)80051-9 ◽

1980 ◽

Vol 2 (4) ◽

pp. 379-386 ◽

Cited By ~ 7

Author(s):

Hideki Horita ◽

Koumei Kumagai ◽

Kihei Maekawa ◽

Shiro Endo

Keyword(s):

Corpus Callosum ◽

Infantile Spasms

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De novo PIK3R2 variant causes polymicrogyria, corpus callosum hyperplasia and focal cortical dysplasia

European Journal of Human Genetics ◽

10.1038/ejhg.2016.7 ◽

2016 ◽

Vol 24 (9) ◽

pp. 1359-1362 ◽

Cited By ~ 12

Author(s):

Gaetano Terrone ◽

Norine Voisin ◽

Ali Abdullah Alfaiz ◽

Gerarda Cappuccio ◽

Giuseppina Vitiello ◽

...

Keyword(s):

Corpus Callosum ◽

De Novo ◽

Focal Cortical Dysplasia ◽

Cortical Dysplasia

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A de novo 163 kb interstitial 1q44 microdeletion in a boy with thin corpus callosum, psychomotor delay and seizures

European Journal of Medical Genetics ◽

10.1016/j.ejmg.2012.08.005 ◽

2012 ◽

Vol 55 (12) ◽

pp. 715-718 ◽

Cited By ~ 5

Author(s):

Kaja K. Selmer ◽

Einar Bryne ◽

Olaug K. Rødningen ◽

Madeleine Fannemel

Keyword(s):

Corpus Callosum ◽

De Novo ◽

Thin Corpus Callosum ◽

Psychomotor Delay

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De novo variants in SUPT16H cause neurodevelopmental disorders associated with corpus callosum abnormalities

Journal of Medical Genetics ◽

10.1136/jmedgenet-2019-106193 ◽

2020 ◽

Vol 57 (7) ◽

pp. 461-465

Author(s):

Roya Bina ◽

Dena Matalon ◽

Brieana Fregeau ◽

Jacqueline Joani Tarsitano ◽

Ingvild Aukrust ◽

...

Keyword(s):

Corpus Callosum ◽

Neurodevelopmental Disorders ◽

Protein Function ◽

De Novo ◽

Chromatin Remodelling ◽

Dysmorphic Features ◽

Whole Exome ◽

Neurodevelopmental Deficits ◽

A Subunit ◽

Genetic Discovery

IntroductionWhole-exome sequencing (WES) has identified de novo variants in chromatin remodelling genes in patients with neurodevelopmental disorders (NDD). We report on a novel genetic discovery in chromatin remodelling in patients with NDD who also have corpus callosum (CC) anomalies.ObjectiveTo discover novel genes linked to both CC anomalies and NDD.MethodsClinical WES was performed for evaluation of NDD, identifying five patients with de novo variants in SUPT16H, a subunit of the FACT (facilitates chromatin transcription) complex. The clinical phenotypes, genetic results and brain MRIs were obtained and systematically reviewed. In silico protein function predictions were assessed and allele frequencies in control populations were compared.ResultsWe identified four patients with de novo missense variants in SUPT16H and one patient with a de novo deletion including SUPT16H. These variants were not reported in the updated Genome Aggregation Database. When assayable, all protein products were predicted to be damaging. Symptoms included intellectual disability, autistic features, minor dysmorphic features and seizures. Anomalies of the CC were seen in all three patients with available brain imaging.ConclusionOur findings implicate the gene SUPT16H in a novel disorder characterised by neurodevelopmental deficits and CC anomalies.

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