Search results for " developmental delay"
showing 10 items of 14 documents
DLG4-related synaptopathy: a new rare brain disorder
2021
Contains fulltext : 245031.pdf (Publisher’s version ) (Closed access) PURPOSE: Postsynaptic density protein-95 (PSD-95), encoded by DLG4, regulates excitatory synaptic function in the brain. Here we present the clinical and genetic features of 53 patients (42 previously unpublished) with DLG4 variants. METHODS: The clinical and genetic information were collected through GeneMatcher collaboration. All the individuals were investigated by local clinicians and the gene variants were identified by clinical exome/genome sequencing. RESULTS: The clinical picture was predominated by early onset global developmental delay, intellectual disability, autism spectrum disorder, and attention deficit-hyp…
De Novo and Inherited Pathogenic Variants in KDM3B Cause Intellectual Disability, Short Stature, and Facial Dysmorphism
2019
Contains fulltext : 202646.pdf (Publisher’s version ) (Open Access) By using exome sequencing and a gene matching approach, we identified de novo and inherited pathogenic variants in KDM3B in 14 unrelated individuals and three affected parents with varying degrees of intellectual disability (ID) or developmental delay (DD) and short stature. The individuals share additional phenotypic features that include feeding difficulties in infancy, joint hypermobility, and characteristic facial features such as a wide mouth, a pointed chin, long ears, and a low columella. Notably, two individuals developed cancer, acute myeloid leukemia and Hodgkin lymphoma, in childhood. KDM3B encodes for a histone …
Heterozygous Variants in KDM4B Lead to Global Developmental Delay and Neuroanatomical Defects
2020
International audience; KDM4B is a lysine-specific demethylase with a preferential activity on H3K9 tri/di-methylation (H3K9me3/2)-modified histones. H3K9 tri/di-demethylation is an important epigenetic mechanism responsible for silencing of gene expression in animal development and cancer. However, the role of KDM4B on human development is still poorly characterized. Through international data sharing, we gathered a cohort of nine individuals with mono-allelic de novo or inherited variants in KDM4B. All individuals presented with dysmorphic features and global developmental delay (GDD) with language and motor skills most affected. Three individuals had a history of seizures, and four had a…
Chromosome 15q BP3 to BP5 deletion is a likely locus for speech delay and language impairment: Report on a four‐member family and an unrelated boy
2020
Abstract Background Deletions in chromosome 15q13 have been reported both in healthy people and individuals with a wide range of behavioral and neuropsychiatric disturbances. Six main breakpoint (BP) subregions (BP1‐BP6) are mapped to the 15q13 region and three further embedded BP regions (BP3‐BP5). The deletion at BP4‐BP5 is the rearrangement most frequently observed compared to other known deletions in BP3‐BP5 and BP3‐BP4 regions. Deletions of each of these three regions have previously been implicated in a variable range of clinical phenotypes, including minor dysmorphism, developmental delay/intellectual disability, epilepsy, autism spectrum disorders, behavioral disturbances, and speec…
Phenotype associated with TAF2 biallelic mutations: a clinical description of four individuals and review of the literature
2021
International audience; Transcription factor IID is a multimeric protein complex that is essential for the initiation of transcription by RNA polymerase II. One of its critical components, the TATA-binding protein-associated factor 2, is encoded by the gene TAF2. Pathogenic variants of this gene have been shown to be responsible for the Mental retardation, autosomal recessive 40 syndrome. This syndrome is characterized by severe intellectual disability, postnatal microcephaly, pyramidal signs and thin corpus callosum. Until now, only three families have been reported separately. Here we report four individuals, from two unrelated families, who present with severe intellectual disability and…
LARGE FOR GESTATIONAL AGE, MACROSOMIA, OVERGROWTH: AN UPDATE ON DEFINITIONS AND DETERMINANTS
2020
Human growth and development, starting from conception, are characterized by a progressive increase in body and organ dimensions, as well as specific functional maturity, under the influence of genetic as well as environmental and epigenetic determinants. Beyond a possible normal familial trait, increased fetal growth resulting in a large for gestational age newborn, isolated macrosomia or that associated with congenital malformation, can be attributable to both maternal metabolic and genetic pathology. Overgrowth syndromes are a heterogeneous group of diseases characterized by excessive tissue development often concomitant to neurodevelopmental involvement. Recently, an increased risk of f…
MACROCEPHALY FROM A NORMAL VARIANT TO A THREATENING CONDITION. A SINGLE CENTER RETROSPECTIVE STUDY ON 189 SUBJECTS
2020
Introduction: Macrocephaly, defined as a head circumference more than two standard deviations from the normal distribution, is among the most frequently requested neuropediatric consultations. Materials: we conducted a retrospective study on 189 subjects with macrocephaly, from birth to 18 years old, enrolled from October 2001 to December 2019, for diagnostic definition and/or neurodevelopmental assessment. Brain sonography has been performed in all infants and CT or MR in selected patients. Results: macrocephaly was prevalent in males (62.4%), a head circumference >3SD (8.5%) has been associated with a neurodevelopmental impairment. A genetic and/or concomitant malformation were present…
A Recurrent De Novo PACS2 Heterozygous Missense Variant Causes Neonatal-Onset Developmental Epileptic Encephalopathy, Facial Dysmorphism, and Cerebel…
2018
International audience; Developmental and epileptic encephalopathies (DEEs) represent a large clinical and genetic heterogeneous group of neurodevelopmental diseases. The identification of pathogenic genetic variants in DEEs remains crucial for deciphering this complex group and for accurately caring for affected individuals (clinical diagnosis, genetic counseling, impacting medical, precision therapy, clinical trials, etc.). Whole-exome sequencing and intensive data sharing identified a recurrent de novo PACS2 heterozygous missense variant in 14 unrelated individuals. Their phenotype was characterized by epilepsy, global developmental delay with or without autism, common cerebellar dysgene…
Novel LRPPRC compound heterozygous mutation in a child with early-onset Leigh syndrome French-Canadian type: Case report of an Italian patient
2020
Abstract Background Mitochondrial diseases, also known as oxidative phosphorylation (OXPHOS) disorders, with a prevalence rate of 1:5000, are the most frequent inherited metabolic diseases. Leigh Syndrome French Canadian type (LSFC), is caused by mutations in the nuclear gene (2p16) leucine-rich pentatricopeptide repeat-containing (LRPPRC). It is an autosomal recessive neurogenetic OXPHOS disorder, phenotypically distinct from other types of Leigh syndrome, with a carrier frequency up to 1:23 and an incidence of 1:2063 in the Saguenay-Lac-St Jean region of Quebec. Recently, LSFC has also been reported outside the French-Canadian population. Patient presentation We report a male Italian (Sic…
Inhibition, set-shifting and working memory in Global Developmental Delay preschool children
2018
Executive functions (EFs) allow to planning and voluntarily and autonomously produce targeted behaviors, in unusual or complex conditions in which the automated response schemes are not appropriate or sufficient to achieve behavior goal. The aim of this study was to evaluate EFs in preschool children presenting with Global Developmental Delay (GDD). Fifty-two preschool children participated in this study: 20 GDD children and 32 typical developing children (TDC) as control group, enrolled in the schools of Campania and Sicily Regions. All subjects underwent evaluation of the executive functioning through the administration of the Battery for the Assessment of Preschool Executive Functions (B…