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

2020 ◽  
Vol 7 (6) ◽  
pp. 956-964 ◽  
Author(s):  
Abdulaziz Asiri ◽  
Essra Aloyouni ◽  
Muhammad Umair ◽  
Yusra Alyafee ◽  
Abeer Al Tuwaijri ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Dysmorphic Feature ◽  
Speech Delay

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

2018 ◽  
Vol 34 (2) ◽  
pp. 86-93 ◽  
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.

scholarly journals MED13L-related intellectual disability due to paternal germinal mosaicism

2021 ◽  
pp. mcs.a006124
Author(s):  
Beata Bessenyei ◽  
Istvan Balogh ◽  
Attila Mokanszki ◽  
Aniko Ujfalusi ◽  
Rolph Pfundt ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Mediator Complex ◽  
Facial Dysmorphism ◽  
Facial Features ◽  
Speech Delay ◽  
Motor Delay ◽  
First Case ◽  
Intragenic Deletion ◽  
Germinal Mosaicism

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.

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

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

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

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 707 ◽  
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.

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

2015 ◽  
Vol 2 (2) ◽  
pp. a000703 ◽  
Author(s):  
Ayşegül Ozantürk ◽  
Erica E. Davis ◽  
Aniko Sabo ◽  
Marjan M. Weiss ◽  
Donna Muzny ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Ambiguous Genitalia ◽  
Facial Dysmorphism ◽  
Speech Delay

scholarly journals Floating-Harbor syndrome: Presentation of the first Romanian patient with a SRCAP mutation and review of the literature

2018 ◽  
Vol 21 (1) ◽  
pp. 83-86
Author(s):  
M Budisteanu ◽  
N Bögershausen ◽  
SM Papuc ◽  
S Moosa ◽  
M Thoenes ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Short Stature ◽  
Clinical Features ◽  
Rare Condition ◽  
Bone Age ◽  
Speech Development ◽  
Speech Delay ◽  
Mild Intellectual Disability ◽  
Intensive Program ◽  
Floating Harbor Syndrome

Abstract Floating-Harbor syndrome (FHS) is a rare autosomal dominant syndrome characterized by short stature with delayed bone age, retarded speech development, intellectual disability and dysmorphic facial features. Recently, dominant mutations almost exclusively clustered in the final exon of the Snf2-related CREBBP activator protein (SRCAP) gene were identified to cause FHS. Here, we report a boy with short stature, speech delay, mild intellectual disability, dysmorphic features, and with genetically confirmed FHS. To the best of our knowledge, this is the first molecularly confirmed case with this syndrome reported in Romania. An intensive program of cognitive and speech stimulation, as well as yearly neurological, psychological, ophthalmological, otorhinolaryngological, pediatric and endocrinological monitoring for our patient were designed. We propose a checklist of clinical features suggestive of FHS, based on the main clinical features, in order to facilitate the diagnosis and clinical management of this rare condition.

MYT1L mutation in a patient causes intellectual disability and early onset of obesity: a case report and review of the literature

2019 ◽  
Vol 32 (4) ◽  
pp. 409-413 ◽  
Author(s):  
Abeer Al Tuwaijri ◽  
Majid Alfadhel
Keyword(s):  
Intellectual Disability ◽  
Early Onset ◽  
De Novo ◽  
Copy Number Variants ◽  
Speech Delay ◽  
Single Nucleotide Variants ◽  
Genome Wide ◽  
Whole Exome ◽  
Syndromic Obesity ◽  
The Central Nervous System

Abstract Background Obesity has become one of the greatest health risks worldwide. Recently, there was an explosion of information regarding the role of the central nervous system (CNS) in the development of monogenic and syndromic obesity. Case presentation Over the last decade, terminal and interstitial submicroscopic deletions of copy number variants (CNVs) in 2p25.3 and single nucleotide variants (SNVs) in myelin transcription factor 1 like (MYT1L) were detected by genome-wide array analysis and whole exome sequencing (WES) in patients with a nonspecific clinical phenotype that commonly includes intellectual disability (ID), early onset of obesity and speech delay. Here, we report the first Saudi female patient with mild to moderate ID, early onset of obesity and speech delay associated with a de novo pathogenic SNV in the MYT1L gene (c. 1585G>A [Gly529Arg]), which causes an amino acid change from Gly to Arg at position 529 that leads to mental retardation, autosomal dominant 39.

scholarly journals Variability of Phenotype in Two Sisters with Pyridoxine Dependent Epilepsy

2012 ◽  
Vol 39 (4) ◽  
pp. 516-519 ◽  
Author(s):  
Majid Alfadhel ◽  
Sandra Sirrs ◽  
Paula J. Waters ◽  
András Szeitz ◽  
Eduard Struys ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Case Report ◽  
Intellectual Disability ◽  
Genetic Background ◽  
Autosomal Recessive ◽  
Vitamin B ◽  
Missense Mutations ◽  
Compound Heterozygosity ◽  
Speech Delay ◽  
Seizure Disorders

Background:Pyridoxine dependent epilepsy (PDE) is characterized by neonatal epileptic encepahalopathy responsive to pharmacological doses of vitamin B6. Recently an autosomal recessive deficiency in Antiquitin (ALDH7A1), a gene involved in the catabolism of lysine has been identified as the underlying cause.Case report:In 21 and 23 year-old sisters, who had presented with neonatal / early infantile onset seizures, PDE was confirmed by elevated urinary alpha aminoadipic- 6- semialdehyde (α-AASA) excretion and compound heterozygosity for two known ALDH7A1 missense mutations. Although epilepsy was well controlled upon treatment with pyridoxine, thiamine, phenytoin and carbamazepine since early infancy, both had developmental delay with prominent speech delay as children. As adults, despite the same genetic background and early treatment with pyridoxine, their degree of intellectual disability (ID) differed widely. While the older sister's cognitive functions were in the moderate ID range and she was not able to live unattended, the younger sister had only mild ID and was able to live independently.Conclusion:Although seizures are a defining feature of PDE, other disease manifestations can vary widely even within the same family. Adult neurologists should be aware that the diagnosis of PDE can be delayed and PDE should be considered in the differential diagnosis of adults with seizure disorders dating from childhood.

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