A t(5;16) translocation is the likely driver of a syndrome with ambiguous genitalia, facial dysmorphism, intellectual disability, and speech delay

The MED13L-related intellectual disability or MRFACD syndrome (Mental retardation and distinctive facial features with or without cardiac defects; MIM # 616789) is one of the most common form of syndromic intellectual disability with about a hundred cases reported so far. Affected individuals share overlapping features comprising intellectual disability, hypotonia, motor delay, remarkable speech delay, and a recognizable facial gestalt. De novo disruption of the MED13L gene by deletions, duplications or sequence variants has been identified deleterious. Siblings affected by intragenic deletion transmitted from a mosaic parent have been reported once in the literature. We now present the first case of paternal germinal mosaicism for a missense MED13L variant causing MRFACD syndrome in one of the father's children and be the likely cause of intellectual disability and facial dysmorphism in the other. As part of the Mediator complex, the MED proteins have an essential role in regulating transcription. 32 subunits of the Mediator complex genes have been linked to congenital malformations that are now acknowledged as transcriptomopathies. The MRFACD syndrome has been suggested to represent a recognizable phenotype.

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Mutations in EBF3 disturb transcriptional profiles and underlie a novel syndrome of intellectual disability, ataxia and facial dysmorphism

10.1101/067454 ◽

2016 ◽

Cited By ~ 2

Author(s):

Frederike Leonie Harms ◽

Katta Mohan Girisha ◽

Andrew A. Hardigan ◽

Fanny Kortüm ◽

Anju Shukla ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Transcriptional Regulation ◽

Intellectual Disability ◽

Neuronal Differentiation ◽

Neuronal Development ◽

Facial Dysmorphism ◽

Rna Seq ◽

Speech Delay

AbstractFrom a GeneMatcher-enabled international collaboration, we identified ten individuals with intellectual disability, speech delay, ataxia and facial dysmorphism and a mutation in EBF3, encoding a transcription factor required for neuronal differentiation. Structural assessments, transactivation assays, in situ fractionation, RNA-seq and ChlP-seq experiments collectively show that the mutations are deleterious and impair EBF3 transcriptional regulation. These findings demonstrate that EBF3-mediated dysregulation of gene expression has profound effects on neuronal development in humans.

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Delineating the Clinical Spectrum Associated With Xq25q26.2 Duplications: Report of 2 Families and Review of the Literature

Journal of Child Neurology ◽

10.1177/0883073818811454 ◽

2018 ◽

Vol 34 (2) ◽

pp. 86-93 ◽

Cited By ~ 2

Author(s):

John C. Herriges ◽

Ellen M. Arch ◽

Pamela A. Burgio ◽

Erin E. Baldwin ◽

Danielle LaGrave ◽

...

Keyword(s):

Intellectual Disability ◽

Learning Difficulties ◽

Growth Failure ◽

Speech Delay ◽

Review Of The Literature ◽

Phenotype Correlation ◽

Additional Insight ◽

Dysmorphic Features ◽

Phenotypic Spectrum ◽

Insight Into

To date, 13 patients with interstitial microduplications involving Xq25q26.2 have been reported. Here, we report 6 additional patients from 2 families with duplications involving Xq25q26.2. Family I carries a 5.3-Mb duplication involving 26 genes. This duplication was identified in 3 patients and was associated with microcephaly, growth failure, developmental delay, and dysmorphic features. Family II carries an overlapping 791-kb duplication that involves 3 genes. This duplication was identified in 3 patients and was associated with learning disability and speech delay. The size and gene content of published overlapping Xq25q26.2 duplications vary, making it difficult to define a critical region or establish a genotype-phenotype correlation. However, patients with overlapping duplications have been found to share common clinical features including microcephaly, growth failure, intellectual disability, learning difficulties, and dysmorphic features. The 2 families presented here provide additional insight into the phenotypic spectrum and clinical significance of duplications in this region.

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Pitt–Hopkins syndrome with electrical stat us epileptic us in slo w-wave sleep: a case report

Russian Journal of Child Neurology ◽

10.17650/2073-8803-2019-14-2-42-48 ◽

2019 ◽

Vol 14 (2) ◽

pp. 42-48

Author(s):

N. G. Lyukshina

Keyword(s):

Case Report ◽

Intellectual Disability ◽

Status Epilepticus ◽

Neuronal Differentiation ◽

Clinical Case ◽

Genetic Disorder ◽

Facial Dysmorphism ◽

Autistic Behavior ◽

Rare Genetic Disorder ◽

Molecular Variant

Pitt–Hoppkins syndrome is rare genetic disorder caused by a molecular variant of TCF4 which is involved in embryologic neuronal differentiation. The syndrome is characterized by specific facial dysmorphism, phychomotor delay, autistic behavior and intellectual disability. Other associated features include ealy-onset myopia, seizures, constipation and hyperventilation-apneic spells. We introduced a clinical case of the patient with molecularly confirmed TCF4 variant and previously undescribed combination with syndrome of the electrical status epilepticus during sleep.

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X-linked intellectual disability-hypotonia-facial dysmorphism-aggressive behavior syndrome

10.32388/ex0hrr ◽

2020 ◽

Author(s):

Keyword(s):

Intellectual Disability ◽

Aggressive Behavior ◽

Facial Dysmorphism ◽

Behavior Syndrome

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Mutated RAP1GDS1 causes a new syndrome of dysmorphic feature, intellectual disability & speech delay

Annals of Clinical and Translational Neurology ◽

10.1002/acn3.51059 ◽

2020 ◽

Vol 7 (6) ◽

pp. 956-964 ◽

Cited By ~ 1

Author(s):

Abdulaziz Asiri ◽

Essra Aloyouni ◽

Muhammad Umair ◽

Yusra Alyafee ◽

Abeer Al Tuwaijri ◽

...

Keyword(s):

Intellectual Disability ◽

Dysmorphic Feature ◽

Speech Delay

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EMC10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay

Clinical Genetics ◽

10.1111/cge.13842 ◽

2020 ◽

Vol 98 (6) ◽

pp. 555-561

Author(s):

Muhammad Umair ◽

Mariam Ballow ◽

Abdulaziz Asiri ◽

Yusra Alyafee ◽

Abeer Tuwaijri ◽

...

Keyword(s):

Intellectual Disability ◽

Developmental Delay ◽

Global Developmental Delay ◽

Speech Delay ◽

Mild Intellectual Disability ◽

Homozygous Variant

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A Private 16q24.2q24.3 Microduplication in a Boy with Intellectual Disability, Speech Delay and Mild Dysmorphic Features

Genes ◽

10.3390/genes11060707 ◽

2020 ◽

Vol 11 (6) ◽

pp. 707 ◽

Cited By ~ 1

Author(s):

Orazio Palumbo ◽

Pietro Palumbo ◽

Ester Di Muro ◽

Luigia Cinque ◽

Antonio Petracca ◽

...

Keyword(s):

Intellectual Disability ◽

De Novo ◽

Chromosome Region ◽

Snp Array ◽

Supporting Evidence ◽

Speech Delay ◽

Dysmorphic Features ◽

Phenotype Comparison ◽

Molecular Comparison ◽

Snp Array Analysis

No data on interstitial microduplications of the 16q24.2q24.3 chromosome region are available in the medical literature and remain extraordinarily rare in public databases. Here, we describe a boy with a de novo 16q24.2q24.3 microduplication at the Single Nucleotide Polymorphism (SNP)-array analysis spanning ~2.2 Mb and encompassing 38 genes. The patient showed mild-to-moderate intellectual disability, speech delay and mild dysmorphic features. In DECIPHER, we found six individuals carrying a “pure” overlapping microduplication. Although available data are very limited, genomic and phenotype comparison of our and previously annotated patients suggested a potential clinical relevance for 16q24.2q24.3 microduplication with a variable and not (yet) recognizable phenotype predominantly affecting cognition. Comparing the cytogenomic data of available individuals allowed us to delineate the smallest region of overlap involving 14 genes. Accordingly, we propose ANKRD11, CDH15, and CTU2 as candidate genes for explaining the related neurodevelopmental manifestations shared by these patients. To the best of our knowledge, this is the first time that a clinical and molecular comparison among patients with overlapping 16q24.2q24.3 microduplication has been done. This study broadens our knowledge of the phenotypic consequences of 16q24.2q24.3 microduplication, providing supporting evidence of an emerging syndrome.

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