Etiology Of Mental Retardation Research Articles

STUDY OF PALMAR CREASES IN CHILDREN WITH MENTAL RETARDATION: A CASE CONTROL STUDY IN TERTIARY HOSPITAL IN NORTH INDIA

Introduction- Etiology of mental retardation is multi-factorial which include various genetic and environmental factors. Minor physical anomalies are commonly observed in these children. Abnormal palmar creases are one of them. Aim-To compare prevalence of abnormal palmar creases in children with mental retardation and typically developing children. Methodology- Case controlled cross sectional study conducted on children with mental retardation and typically developing normal children. Photographs of palm were clicked using high resolution camera, digitally saved and evaluated later on. Results- The prevalence of abnormal palmar creases is increased in children with mental retardation. Correlation between increasing severity of mental retardation and abnormal palmar creases was noticed only in the right hand. Conclusion- Abnormal palmar creases are one of the minor physical anomalies found in children with mental retardation. Its presence would prompt clinicians for early screening and diagnosis which would increase possibility of early intervention.

The Etiology of Mental Retardation in Iraqi Children.

Abstract Background: Mental retardation is a group of heterogeneous disorders associated with generalized developmental delay during infancy and early childhood, while impairment in cognitive functions and adaptive behaviors became generally apparent during pre-school and early school years depending on the severity of the condition. Little is known about the etiology of mental retardation in Iraq. The aim of this paper is to describe the etiology of mental retardation in a sample of Iraqi children. Patients and methods: During one-year period (February 2018 to February 2019), thirty-six patients with mental retardation (25 males and 11 females) were observed at the neuropsychiatry clinic at the Children Teaching hospital of Baghdad Medical City. Their ages ranged from two to seventeen years. Patients with cerebral palsy, atypical autism with mental retardation and Rett syndrome were not included in this series. Results: Eighteen patients (50%) had idiopathic mental retardation (11 males and 7 females). Seven patients (19%) had Down syndrome (5 males and 2 females). Two male patients had Beckwith Wiedemann syndrome, one of them had an affected brother. Three males had inborn errors of metabolism, each one had phenylketonuria, homocystinuria and Lesch Nyhan syndrome. The patient with Lesch Nyhan syndrome had an older brother who died from the same condition. Six patients each one had Prader-Labhart-Willi syndrome, Sanjad Sakati Richardson Kirk syndrome, Coffin Siris syndrome, kernicterus, Bartter syndrome, Pediatric Huntington disease. Nonspecific abnormalities were present in three patients and included bilateral optic atrophy in one boy, squint and obesity in one girl and a second girl had large ears. Brain CT-scan was available for two patients with idiopathic mental retardation and one patient with kernicterus and showed normal findings. Conclusion: The causes of mental retardation in about two thirds of Iraqi patients with mental retardation were idiopathic mental retardation and Down syndrome.

The etiology of mental retardation in Iraqi children

The etiology of mental retardation in Iraqi children

The Effects of Robotic Gait Rehabilitation on Psychosomatic Indicators at the People with Different Etiology of Mental Retardation

The Effects of Robotic Gait Rehabilitation on Psychosomatic Indicators at the People with Different Etiology of Mental Retardation

Cytogenetic analysis in a large series of children with non-syndromic mental retardation.

Mental retardation affects 1-3% of the population. To evaluate the implication of chromosomal abnormalities in the etiology of mental retardation, 1420 patients with non-syndromic mental retardation recruited at the department of cytogenetics of Farhat Hached hospital (Sousse, Tunisia) between January 2005 and December 2009, were analyzed using standard cytogenetic techniques. Age ranged between 3 and 18 years with a median of 8 years. Chromosomal abnormalities were detected in 7.8% of patients and an increased prevalence of chromosome anomalies was observed in patients when the mental retardation is associated with a severe degree of intellectual disability, facial dysmorphic features and/or congenital malformations or epilepsy.

The founder of an institution: Robert E. Cooke and the NIHCD.

Courtesy of the NIH. Robert E. Cooke was born in Attleboro, Massachusetts, and earned his B.S. at Yale's Sheffield Scientific School, in 1941, and his M.D. at the Yale School of Medicine, in 1944. He completed his internship and residency at the New Haven Hospital, with an intervening period of service in the U.S. Army Medical Corps. In 1956, Cooke joined The Johns Hopkins University School of Medicine as professor and chair of the pediatrics department, at which time he began attending to the needs of underserved mothers and their children and for those with mental health challenges. From his base at Johns Hopkins, Dr. Cooke directed the Kennedy Program for Research into the Etiology of Mental Retardation, led the task force that recommended establishing the National Institute of Child Health and Human Development (NICHD), and helped implement the national Head Start program to help children born into poverty overcome social and education obstacles. Dr. Cooke was a close friend and pediatrician of the Shriver family. Dr. Cooke and Eunice Kennedy Shriver, the sister of then President John F. Kennedy, are considered to be the driving forces behind the establishment of the NIHCD. In the late 1950s, Dr. Cooke began advising Mrs. Shriver as she headed the Joseph P. Kennedy Jr. Foundation, which was dedicated to confronting issues related to intellectual and developmental disabilities. In an interview for the NICHD's 50th anniversary in 2012, Dr. Cooke recounted his involvement: “I was a good friend with Eunice Shriver and when the president was elected, before he took office, they put together a task force to look at health and social services for the new administration. And I got a telephone call one day asking me if I could serve on this task force.” The task force's report highlighted the lack of research on the physical, intellectual, and emotional growth of children, and recommended the establishment of an agency to investigate disorders of human development, including intellectual and developmental pathologies. The NICHD was initially founded to support research on human development throughout the entire life process, focusing on understanding intellectual and developmental disabilities - a focus that was virtually non-existent at the time. As in all eras, resistance came from leaders in the scientific community, who felt that funds would be better spent supporting more productive fields of research. Mrs. Shriver did not back down, instead publicly stressing the positive impact this research would have towards understanding general human development. For her efforts, Congress renamed the institute the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The early years of the Institute were both exciting and challenging. At that time, it was difficult to find researchers, physicians, and educators willing to pursue this new field of study. But, with the support of Congress, the NICHD recruited a cadre of some of the most accomplished researchers in the country, some of whom became directors of the 12 new Institute research centers established by the task-force plan. Dr. Cooke continued his involvement with the NICHD after its founding. He served as a member of the Institute's advisory body, the National Advisory Child Health and Human Development Council, the NICHD Intramural program's Board of Scientific Councilors, and the Advisory Board for the NICHD's National Center for Medical Rehabilitation Research. In his 2012 interview, Dr. Cooke added that the NICHD has proven its value over its 50-year history: “My feeling is that NICHD has made an enormous contribution to children in this country and, I think, to medicine in general…. What you do for the child seems to make an enormous difference in his life.” “Dr. Cooke cared deeply about the health and well being of children—those least able to make their needs known to our country's leadership,” said Dr. Alan E. Guttmacher, current Director of the Eunice Kennedy Shriver NICHD. “The NICHD came into existence largely due to his foresight and determination and, to this day, serves as a tribute to his efforts.” Adapted from: www.nichd.nih.gov/news/releases/Pages/031814-cooke-obituary.aspx www.medicalarchives.jhmi.edu/papers/cooke.html Gary M. Wessel

Evolution of the Discs large gene family provides new insights into the establishment of apical epithelial polarity and the etiology of mental retardation

Cell polarity is essential to the function of many cell types, such as epithelial cells and neurons. The Discs large (Dlg) scaffolding protein was identified in Drosophila as a major regulator of basolateral epithelial identity. Four Dlg orthologs (Dlg1 through 4) are found in vertebrates, and mutations in the human Dlg3 gene are associated with X-linked mental retardation. We recently found that Dlg3 controls apical epithelial polarity and tight junction formation and contributes to neural induction in mouse development.1 During evolution, Dlg3 acquired specific PPxY motifs, which bind to the WW domains of the E3 ubiquitin ligases, Nedd4 and Nedd4-2. This interaction results in monoubiquitination of Dlg3, leading to directed microtubule-dependent protein trafficking, via the exocyst complex, in different polarized cell types. Directed trafficking of Dlg3 plays an important role, during both mammalian development and in adulthood, in the establishment and maintenance of specialized apical cell junctions, such as tight junctions in epithelial cells and synapses in neurons.

Positive Association ofCC2D1AandCC2D2AGene Haplotypes with Mental Retardation in a Han Chinese Population

The CC2D1A and CC2D2A genes are involved in Ca(2+)-regulated signaling pathways and have recently been implicated in the etiology of mental retardation (MR). The aim of this study was to investigate whether CC2D1A and CC2D2A polymorphisms are associated with susceptibility to MR in a Han Chinese population using a family based association approach. The sample included 172 trios (parents and offspring), and all subjects were genotyped for several single-nucleotide polymorphisms covering CC2D1A and CC2D2A. Linkage disequilibrium (LD) analysis revealed that the rs6511901 and rs10410239 polymorphisms of CC2D1A were in strong LD (D'=0.865), and haplotype analysis showed evidence for over-transmission from parents to MR offspring (p=0.0009). The LD analysis also revealed that CC2D2A single-nucleotide polymorphisms rs10025837, rs13116304, and rs7661102 were in strong LD (D'=0.848), and haplotype analysis showed significant transmission disequilibrium (p=0.0004). The results suggest the involvement of CC2D1A and CC2D2A in MR in the Han Chinese population, and some specific haplotypes may be susceptible or protective.

Whole‐genome array CGH identifies pathogenic copy number variations in fetuses with major malformations and a normal karyotype

Despite a wide range of clinical tools, the etiology of mental retardation and multiple congenital malformations remains unknown for many patients. Array-based comparative genomic hybridization (aCGH) has proven to be a valuable tool in these cases, as its pangenomic coverage allows the identification of chromosomal aberrations that are undetectable by other genetic methods targeting specific genomic regions. Therefore, aCGH is increasingly used in clinical genetics, both in the postnatal and the prenatal settings. While the diagnostic yield in the postnatal population has been established at 10-12%, studies investigating fetuses have reported variable results. We used whole-genome aCGH to investigate fetuses presenting at least one major malformation detected on ultrasound, but for whom standard genetic analyses (including karyotype) failed to provide a diagnosis. We identified a clinically significant chromosomal aberration in 8.2% of tested fetuses (4/49), and a result of unclear clinical significance in 12.2% of tested fetuses (6/49). Our results document the value of whole-genome aCGH as a prenatal diagnostic tool and highlight the interpretation difficulties associated with copy number variations of unclear significance.

813 Cytogenetic Results of 153 Patients with Mental Retardation in Middle Anatolia in Turkey

Mental retardation (MR), that is s a major social, educational, and health problem, occurs with the prevalence of 1-3% of general population. The etiologies of MR are complex the cause remains unknown in about 50% of cases and include teratogenic and environmental factors, perinatal asphyxia and genetic causes. Cytogenetic studies have been reported to determine the contribution of chromosomal abnormalities in parents with mental retardation from various other countries. As far as we know, no enaught studies have been done in the middle Anatolia in Turkey. The aim of the present study was to evaluate the frequency and nature of chromosomal aberrations in Turkish patients that contribute to mental retardation.

Disruption of ST5 is associated with mental retardation and multiple congenital anomalies

BackgroundThe authors observed a patient with a cryptic subtelomeric de novo balanced translocation 46,XY.ish t(11;20)(p15.4;q13.2) presenting with severe mental retardation, muscular hypotonia, seizures, bilateral sensorineural hearing loss, submucous cleft palate,...

Etiologic evaluation of genetically-caused mental retardation. Diagnostic algorithm and new molecular techniques

Mental retardation affects 1-3% of the population. Its etiology is heterogeneous and approximately 47% of cases are caused by genetic factors. The aim of this paper is to report on etiologies of mental retardation, to present updates on new technologies of molecular diagnosis, and to analyze their limitations for the appropriate and rational use of them. Finally, an algorithm based on genetics is suggested for the study of mental retardation by reporting on the techniques available in Argentina and in developed countries. A well-defined etiology will lead to the proper management of children with mental retardation, and suitable family counseling.

Identification of subtelomeric genomic imbalances and breakpoint mapping with quantitative PCR in 296 individuals with congenital defects and/or mental retardation

BackgroundSubmicroscopic imbalances in the subtelomeric regions of the chromosomes are considered to play an important role in the aetiology of mental retardation (MR). The aim of the study was to evaluate a quantitative PCR (qPCR) protocol established by Boehm et al. (2004) in the clinical routine of subtelomeric testing.Results296 patients with MR and a normal karyotype (500–550 bands) were screened for subtelomeric imbalances by using qPCR combined with SYBR green detection. In total, 17 patients (5.8%) with 20 subtelomeric imbalances were identified. Six of the aberrations (2%) were classified as causative for the symptoms, because they occurred either de novo in the patients (5 cases) or the aberration were be detected in the patient and an equally affected parent (1 case). The extent of the deletions ranged from 1.8 to approximately 10 Mb, duplications were 1.8 to approximately 5 Mb in size. In 6 patients, the copy number variations (CNVs) were rated as benign polymorphisms, and the clinical relevance of these CNVs remains unclear in 5 patients (1.7%). Therefore, the overall frequency of clinically relevant imbalances ranges between 2% and 3.7% in our cohort.ConclusionThis study illustrates that the qPCR/SYBR green technique represents a rapid and versatile method for the detection of subtelomeric imbalances and the option to map the breakpoint. Thus, this technique is highly suitable for genotype/phenotype studies in patients with MR/developmental delay and/or congenital defects.

Lack of association between MTHFR C677T and MTHFR A1298C genetic polymorphisms and mental retardation

Findings suggest that there is no association between MTHFR C677T and MTHFR A1298C and mental retardation in the studied Italian population and that these polymorphisms are not contributing to the aetiology of mental retardation.

A loss‐of‐function mutation in the FTSJ1 gene causes nonsyndromic X‐linked mental retardation in a japanese family

Mental retardation (MR) is a common trait, affecting approximately 2-3% of individuals in the general population. Although the etiology of MR remains largely unknown, genetics apparently play a major role. Recent molecular studies of X-linked form of MR in European and North American countries have revealed 24 nonsyndromic X-linked mental retardation (NS-XLMR) genes including FTSJ1, a human homolog of the Escherichia coli 2'-O-rRNA methyltransferase FtsJ/RrmJ gene. Here we identified a novel FTSJ1 mutation in an XLMR family through mutation screening of a cohort of 73 unrelated Japanese male probands with MR. Sequence analysis of the proband and his mother revealed a G > A substitution at the consensus for the donor splicing site in intron 8 (c.571 + 1G > A) of FTSJ1. This mutation prevented the removal intron 8 from the pre-mRNA, thereby leading to a frameshift in the mutant FTSJ1 mRNA and resulting in a premature termination in exon 9. Quantitative RT-PCR showed a significant reduction of mutant FTSJ1 mRNA in the patient's lymphoblast cells, which was restored by treatment with cycloheximide, a potent inhibitor of nonsense-mediated mRNA decay (NMD). Therefore, mRNAs carrying this mutation are likely subject to degradation by NMD. Together, loss-of-function of FTSJ1 may be a mechanism for the cognitive dysfunction observed in this family. Our study also suggested that the FTSJ1 mutation probably accounts for XLMR in Japanese at a similar frequency (1-2%) as in Europeans.

Finding new etiologies of mental retardation and hypotonia: X marks the spot

Mental retardation (MR) and hypotonia occur together frequently and have a heterogeneous etiology. Molecular and clinical studies have led to the recent discovery of genes on the X chromosome that may be associated with syndromal forms of X-linked MR (XLMR). These disorders manifest additional neurological and somatic features that are helpful in establishing a specific diagnosis and etiology. This article provides an overview of MR and its association with hypotonia, with a review of five 'new' XLMR-hypotonia syndromes.

Variants in the RAB3A gene are not associated with mental retardation in the Chinese population

Mental retardation is a common form of cognitive impairment among children. The underlying causes of mental retardation are extremely heterogeneous, and include significant genetic factors. The coexistence of neuropathology and cognitive deficits supports the view that mental retardation is a disorder of brain development and plasticity. Rab3A, a member of the Rab small G protein family, is a key molecule in modulating basal neurotransmission and contributes to synaptic plasticity. The RAB3A gene is located on chromosome 19p13.11, near a region shown by a linkage study to be involved in the etiology of mental retardation. Because of both its function and chromosomal location, RAB3A is a potential candidate susceptibility gene for mental retardation. To investigate the possible genetic contribution of the RAB3A gene, we performed a case-control association study focused on the Han population of northwestern China using four common SNPs in the gene (rs7259012, rs17683539, rs2271882, and rs874628). Pairwise linkage disequilibrium analysis showed that the four SNPs were in linkage disequilibrium. However, there were no significant differences of either allele or genotype frequencies at any of the SNPs nor any significant differences in haplotype distributions between cases and controls. In conclusion, we have found no evidence for RAB3A conferring susceptibility on mental retardation in the Han Chinese population.

The ARX mutations: A frequent cause of X‐linked mental retardation

The ARX gene mutations have been demonstrated to cause different forms of mental retardation (MR). Beside FMR1, in families with X-linked mental retardation (XLMR), the ARX dysfunction was demonstrated to be among the most frequent causes of this heterogeneous group of disorders. Nevertheless, in sporadic cases of MR, ARX mutations are extremely rare. In order to evaluate the frequency of ARX mutation in XLMR, we performed mutational analysis of ARX in 165 mentally retarded probands negative for FRAXA and belonging to families in which the condition segregates as an X-linked condition. The same recurrent mutation, an in frame 24 bp insertion (c.428-451 dup (24 bp)), was identified in five patients. In one family, the mother of two affected boys was found not to carry the mutation detected in her sons. These data suggest the presence of germline mosaicism for the mutation in the mother. Our results confirm the significant contribution of ARX mutations in the etiology of MR, especially in this group of patients selected for XLMR (3%). These data, together with those reported in the literature, imply that screening for c.428-451 dup (24 bp) mutation should be recommended in all patients with suspected XLMR.

The behavioural neurogenetics of Fragile X syndrome: a model of gene-brain behaviour relationships

Results The syndrome is the most important X-linked etiology of mental retardation and developmental disability currently known. The physical, cognitive and behavioural features of individuals with fragile X syndrome depend on gender (females have two X chromosomes, one active and one inactive) and the molecular status of the mutation (permutation, full mutation or mosaic). Features of the behavioural profile of individuals with fragile X syndrome include hypersensitivity to stimuli, overarousability, inattention, hyperactivity and (mostly in men) explosive and aggressive behaviour to others or self. Accumulating evidence also indicates that male and female carriers of the fragile X genetic abnormality demonstrate a relatively specific pattern of psychiatric disturbance. Other anxiety disorders such as social anxiety, depression, impulse control disorder and mood disorders are the most common psychiatric disorders diagnosed in individuals with fragile X syndrome. Discussion Analyzing gene-brain-behavior linkages in childhood neurodevelopmental disorders, a research approach called behavioural neurogenetics, has provided new insights into understanding how both genetic and environmental factors contribute to complex variations in typical and atypical human development. Our research and that of others demonstrates that neurobehavioural and neurocognition, genetics, and neuroanatomy are all different views of the same intriguing biological puzzle; a puzzle that today is rapidly emerging into a more complete picture of the intricate linkages among gene, brain, and behavior in developing children. from International Society on Brain and Behaviour: 2nd International Congress on Brain and Behaviour Thessaloniki, Greece. 17–20 November 2005

Advanced microscopic imaging methods to investigate cortical development and the etiology of mental retardation

Studies on human patients and animal models of disease have shown that disruptions in prenatal and early postnatal brain development are a root cause of mental retardation. Since proper brain development is achieved by a strict spatiotemporal control of neurogenesis, cell migration, and patterning of synapses, abnormalities in one or more of these events during prenatal development can lead to cognitive dysfunction after birth. Many of underlying causes of mental retardation must therefore be studied in developing brains. To aid in this research, live imaging using laser scanning microscopy (LSM) has recently allowed neuroscientists to delve deeply into the complex three-dimensional environment of the living brain to record dynamic cellular events over time. This review will highlight recent examples of how LSM is being applied to elucidate both normal and abnormal cortical development.