Idiopathic Mental Retardation Research Articles

Treatment of a Boy with Idiopathic Mental Retardation: From Uneducable to Educable.

Abstract Background: Mental retardation has been recently called by the American Psychiatric Association “Intellectual disability”, despite that the World Health Organization is still using the term “Mental retardation” in its ICD-10 publication. It is a heterogeneous condition marked by generalized neurodevelopmental abnormalities associated with significant impairment in mental or intellectual functioning and adaptive behaviors that affect every day general living. Patients and methods: A comprehensive multi-factorial treatment approach was used to treat a boy with idiopathic (Moderate to severe) mental retardation who was uneducable with the main aim of making him more educable. Treatment courses included intramuscular citicoline, piracetam, cerebrolysin and oral pyritinol. Results: Treatment was successful in advancing the mental and cognitive functions of the patient and making the child perfectly educable. Conclusion: There is no single agent that is known to convert an educable mentally retarded child to perfectly educable. Idiopathic mental retardation is a heterogeneous condition and the use of multi-factorial therapeutic agents is suggested for its treatment.

Treatment of a boy with idiopathic mental retardation: From uneducable to educable

Treatment of a boy with idiopathic mental retardation: From uneducable to educable

Treatment of A Boy with Idiopathic Mental Retardation: From Uneducable to Educable

Mental retardation is heterogeneous a condition marked by generalized neurodevelopmental abnormalities associated...

Chronic Cutaneous Disorders in Down syndrome Patients

Background: Down syndrome is an extensively studied chromosomal disorder characterized by mental retardation and distinct physical manifestations, and it is the second most common cause of mental retardation in Iraqi children after idiopathic mental retardation. However, the chronic cutaneous conditions associated with the syndrome have received relatively inadequate attention. This paper aims to determine chronic cutaneous disorders persisting more than six months or reoccurring over six months in Down syndrome patients. Patients and Methods: Twenty-seven patients (17 males and 10 females) with Down syndrome were observed at the Children Teaching Hospital of Baghdad medical City and the Medical Consultation Clinic of Iraq headquarter of Copernicus Scientists international panel in Baghdad during 2018 and 2019. Their ages when they were first seen ranged from 4 months to 30 years. Results: Chronic cutaneous disorders were observed in four patients of the twenty-seven patients observed. Three patients including a thirteen-year-old girl and two boys had alopecia areata, and a man aged thirty years had familial baldness and Tinea corporis of the dorsum of the right hand. Conclusions: This paper highlights the association between Down syndrome and Tinea corporis which has not been noticeably emphasized in the medical literature.

A Unique Experience with Mental and Developmental Retardation: Innovative Medical Therapies for Idiopathic Mental Retardation

A Unique Experience with Mental and Developmental Retardation: Innovative Medical Therapies for Idiopathic Mental Retardation

Association of Calcineurin B (PPP3R1) Functional Gene Polymorphism in South Indian Children with Idiopathic Mental Retardation

The present study aims to evaluate the possible association of PPP3R1 gene polymorphism (CnB 5I/5D) in clinical presentation of mental retardation (MR). A total of 100 children with idiopathic mental retardation in the age group of 5-16 years from both the sexes were recruited in the study considering age and sex matched healthy controls. Both cases and controls were genotyped by Polymerase Chain Reaction - Restriction Fragment Length Polymorphism (PCR-RFLP) method for a single nucleotide polymorphism in PPP3R1 gene. The psychometric analysis of 100 MR children indicated that 3% of the children had borderline degree of retardation in which 42% of them were mild, 25% of them were moderate, 30% of them had severe degree of retardation. All the subjects included in the study were categorized based on their clinical and dysmorphic features. Among them 54% had behavioural disorders, 9% had cerebral palsy, 8% had microcephaly, 18% had convulsions and 11% had epilepsy. A significant association was observed for genetic variation at PPP3R1 (CnB 5I/5D) and MR [p < 0.04]. The results revealed that PPP3R1 (CnB 5I/5D) gene polymorphism is associated with MR. Insilico analysis of gene polymorphism i.e., CnB 5I/5D showed absence of TBP binding and may be responsible for low levels of calcineurin. Since calcineurin is involved in biosynthesis and release of neurotransmitter, the low levels of calcineurin and the associated gene polymorphism may be involved in causation of mental retardation.

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.

Development and clinical application of an innovative fluorescence in situ hybridization technique which detects submicroscopic rearrangements involving telomeres.

We report an innovative fluorescence in situ hybridization technique which exploits a unique resource of 41 telomere-specific probes and allows the simultaneous analysis of the subtelomeric region of every chromosome for deletion, triplication and balanced translocation events. This technique requires only a single microscope slide per patient and is expected to be a useful diagnostic tool with applications in the fields of idiopathic mental retardation, the detection of congenital abnormalities and in some forms of cancer. This will lead to more accurate genetic counselling of patients and their families and will provide the basis for future diagnostic, therapeutic and preventative measures.

Array-CGH in pediatric neurology: A prospective observational study

Array-comparative genomic hybridization (Array-CGH) has been proposed as the first efficient approach to scan the entire genome for variations in DNA copy number. This diagnostic method is based on the study of total genomic DNA isolated from any sample and reference cell populations, differentially labelled and hybridized to DNA microarrays. The method has been initially applied in clinical genetics research and has recently also been used in cancer research, as tumor genomes have a wide variety of copy number phenotypes, indicating different types of genetic instability. In this field, array-CGH has been demonstrated to be an efficient diagnostic method to provide information on the location of important cancer genes. Recently the use of array-CGH has been expanded, including the analysis of constitutional abnormalities, to diagnose subtending mutations of neurologic diseases, with promising results in diagnosing genetic mutations otherwise not evident with other genetic tests. We performed a prospective study on the efficiency of array-CGH in the genetic-molecular diagnosis of pediatric patients affected by developmental delay and mental retardation associated with clinical signs of dimorphism and/or other relevant neurological symptoms. In our study, we had a detection rate of 22.71% by array-CGH analysis and we were able to take more precise genetic information for microdeletion and microduplication of our cohort of patients with developmental delay and/or idiopathic mental retardation and/or dimorphic face and/or epilepsy. In our opinion, we think that these findings would be helpful in early diagnosis and family genetic counseling, above all in those clinical neurologic cases in which other diagnostic tests have not succeed in performing a diagnosis.

Chromosomal Abnormalities in Idiopathic Mental Retardation Patients at a Charity Center in Hamadan, Iran

Background: Chromosomal aberrations are one of the most common causes of mental retardation (MR). Objectives: In this study, in order to identify the rate of chromosomal abnormalities in idiopathic MR, 50 MR patients at a charity center in Hamadan, Iran, were investigated. Methods: Fifty mentally retarded male patients without specific chromosomal abnormalities (e.g., Down syndrome, Fragile X syndrome, and Klinefelter syndrome) were included in the study. Standard cytogenetic techniques and high resolution GTG banding were performed on all the patients. Results: All the patients were male, with a mean age of 37.12 years. Skeletal and facial abnormalities were found in 8% and 22% of patients, respectively. All the patients showed a moderate to severe level of mental retardation. None of the patients had numerical chromosome abnormalities. Twoout of the 50 patients (4%) demonstrated structural chromosomal abnormalities. One patient had a paracentric inversion in chromosome 1, while the other had a pericentric inversion in chromosome 2. Conclusions: The presence of structural chromosomal abnormalities (4%) in the studied MR patient population emphasizes the importance of cytogenetic investigation for all idiopathic MR patients.

Application of BoBs technique for detecting common chromosome microdeletion and microduplication syndromes

To establish a strategy for screening and diagnosing common microdeletion and microduplication syndromes among children with idiopathic mental retardation and development abnormalities. Potential chromosomal variations among patients with unexplained mental retardation, cardiac anomalies, particular facial features, learning disabilities and other clinical characteristics were detected with bacterial artificial chromosome BACs-on-Beads (BoBs) technique and karyotyping. Positive results were verified with array-based comparative genomic hybridization (Array-CGH). Fifty eight of the 60 patients had a normal chromosome karyotype. Ten patients with microdeletion and microduplication syndromes were detected by BoBs, which included two positive cases identified through chromosome karyotyping. Two patients were respectively diagnosed as Smith-Magenis syndrome and Prader-Willi/Angelman syndrome by BoBs and the results were confirmed by Array-CGH. BoBs is capable of detecting chromosome microdeletion and microduplication with high specificity and throughput, which can compensate the shortcomings of conventional cytogenetic technology and will be widely applied for clinical diagnosis.

Molecular characterization of X chromosome fragility in idiopathic mental retardation

BackgroundFragile X syndrome (FXS) is the most common form of inherited mental retardation. Frequency of fragile X syndrome among male siblings and relatives of mentally retarded patients is relatively high. Cytogenetic diagnosis of FXS is unreliable since it is ineffective for the diagnosis of premutated males or females. Proper molecular diagnosis is a pre-requisite for providing proper counseling advice. Subjects and methodsSixty-four males with idiopathic mental retardation, ranging in age from 4.2 to 19years (10.92±4.00) were clinically pre-selected, based on scoring protocol comprising eight features of the syndrome, before molecular testing. A rapid polymerase chain reaction-based screening was applied for detection of expanded FMR1 alleles. Samples that did not yield the normal band lengths were subjected to a second PCR screen. The secondary screen utilizes a chimeric primer demonstrating the presence or absence of an expanded allele. ResultsAmplification of FMRI gene by PCR of tested patients revealed that 8 cases (12.5%) have full mutation and 6 cases (9.4%) have premutation. A wide range of Fra X-scoring ranging from 1 to 7 features was detected in examined cases. Significant clinical features included large prominent ears, hyperextensibility of joints and macroorchidism in post pubertal males. ConclusionsA simplified checklist of fragile X should be used for patients with idiopathic MR and those patients above score 3 should be tested for FXS. The diagnostic assay may be used as a screening method for fragile X syndrome being rapid and cost effective compared to other techniques. In addition, screening of all relatives of proven patients should be performed to detect clinically unidentified cases for provision of proper counseling and optimal management of detected cases.

Subtelomeric aberrations in Thai patients with idiopathic mental retardation and autism detected by multiplex ligation-dependent probe amplification

Background: Chromosomal rearrangements involving telomeres account for approximately 1%–30% of causes of mental retardation (MR). It is therefore recommended that all cases of undiagnosed MR be screened for subtelomeric aberration. Nevertheless, resolution of a standard karyotyping using the G-banding technique is limited. Therefore, an additional technique with higher resolution should be performed to detect this type of anomaly. Objectives: To screen for subtelomeric aberration in Thai patients with mental retardation and autism. Methods: Multiplex ligation-dependent probe amplification (MLPA), was used to screen 114 Thai patients with idiopathic MR and 15 patients with autism. All positive results were confirmed by using a different set of MLPA probes or real-time PCR. Results: We identified 5 patients with submicroscopic aberration in patients with MR. One patient had a submicroscopic deletion at the 1p36.33 region, which was confirmed by real-time PCR. There were 2 patients with subtelomeric duplication at the 15q11.2 and 11p15.5 regions sequentially. Two patients had the same duplication at the Xp22.33. region. Conclusions: The present study shows that the incidence of a subtelomeric aberration in Thai patients with idiopathic MR is approximately the same reported previously (3.9%). Identifying these submicroscopic aberrations requires an advanced method with higher resolution than standard karyotyping. Although microarray techniques may be a more informative, they are costly and require an array facility, which are not widely available, especially in developing countries. Thus, MLPA in a routine cytogenetic test for MR patients with normal karyotypes in this setting can help to increase diagnostic yield. Keywords: Autism, mental retardation, MLPA, subtelomere

Screening of mentally handicapped Egyptian children for fragile X syndrome using clinical, cytogenetic and molecular approaches

Abstract . To screen children with idiopathic mental retardation (MR) using a clinical Ten-Item Checklist (TIC) and to analyzehigh-risk fragile X syndrome (FXS) cases by cytogenetic and molecular genetic techniques. This study was conducted on 192children with idiopathic MR enrolled from Pediatric clinics of University Hospitals and MR institutes of Alexandria, Mansouraand Benha Governorates, Nile Delta, Egypt (age range 2–14 years). Clinical scoring for patients was done using TIC according towhich patients were categorized either positive checklist withscore higher than 5 or negative with score less than 5. Positive casesunderwent cytogenetic analysis that provoke expression of fragile sites on chromosome X and molecular genetic analysis fordetection of permutation among cases or their 1st degree relatives. Analyzing all cases: IQ ranged from 30 to 80%, family historyof MR was found in 28.6% and consanguinity was positive in 26%. Positive checklist cases constituted 23.9% and remainder76.1% were negative checklist. The most frequent items in positive cases were large prominent ears, hyper-extensible fingerjoints, hyperactivity, and large narrow face with less common macro-orchidism. A positive linear association was found betweenlaboratory test positivity and TIC score being stronger with cytogenetic analysis compared to polymerase chain reaction (PCR)(P 0.001 and 0.02, respectively). Using TIC, 76.1% cases could be eliminated from the waiting list of genetics laboratories. Therelatively weaker association of TIC score to PCR compared to cytogenetic analysis together with areas under receiver operatingcharacteristic curve 0.743 and 0.814 respectively denote the higher accuracy and sensitivity of PCR analysis in final diagnosis ofFXS.Keywords: Fragile X syndrome, cytogenetics, molecular genetics, Egypt

Clinical characterization and genotype analysis of idiopathic mental retardation in male patients with epilepsy

Objective To detect genetic causes of idiopathic mental retardation /developmental delay in 20 male patients with epilepsy and to analyze their clinical characteristics of positive mutation carriers. Methods The families, consisted of the patient and his parents were recruited.Genomic DNA was extracted from peripheral blood, and candidate gene mutation screening was carried out by next-generation sequencing technology.Mutations in positive gene were verified by polymerase chain reaction(PCR) and direct sequencing. Results Three missense mutations were identified among 3 patients out of 20 cases, with a detection rate of 15%.They were: OPHN1 gene c. 1996 C>G, RAB39B gene c. 542 C>T and AFF2 gene c. 427 A>T, none of which had been reported before.All of these mutations were likely to be pathogenic based on gene function, evolutionary conservation, variant frequency in normal population(NHLBI Exome Sequencing Project and 1 000 Genomes), bioinformatics prediction and inheritance patterns.In addition, all 3 genes disrupted were residing on the X chromosome previously demonstrated to be associated with X-linked mental retardation(XLMR), indicating that they were probably pathogenic or might serve as one of the risk factors. Conclusions Abnormal function of genes on the X chromosomal is one of the most impotent causes of XLMR.X chromosomal gene mutation screening would be recommended for male children suffering from idiopathic mental retardation with epilepsy. Key words: Mental retardation; Epilepsy; Male; Gene mutation

Pathologic Genomic Rearrangements in Idiopathic Mentally Retarded Patients from Iran

Background: Mental retardation is a relatively frequent disorder and occurs in 1-3% of the general population. Chromosomal rearrangements involving microdeletion and microduplication particularly in subtelomeric regions are involved as a significant cause of idiopathic mental retardation. This study was designed to detect these aberrations in the Iranian patients with idiopathic mental retardation. Seventy six patients with unexplained MR, a normal conventional karyotype and negative for fragile X without a clinically recognizable syndrome were included in our study. We used a combination of MLPA kits procured from MRC Holland to increase the detection rate of chromosomal abnormalities in idiopathic MR patients. These kits included P036 and P070 for subtelomeric screening, and in addition P064 and P096 for the 16 common microdeletion syndromes. Results: The MLPA analysis revealed chromosomal aberrations in 8 cases. Conclusion: Using the combination of four MLPA kits the rate of chromosomal abnormality detection in our study was 10.52% which confirms the previous published findings.

Identification of Chromosome Abnormalities in Subtelomeric Regions Using Multiplex Ligation Dependent Probe Amplification (MLPA) Technique in 100 Iranian Patients With Idiopathic Mental Retardation

BackgroundMental retardation/Developmental delay (MR/DD) is present in 1 - 3% of the general population (1, 2). MR is defined as a significant impairment of both cognitive (IQ < 70) and social adaptive functions, with onset before 18 years of age.ObjectivesThe purpose was to determine the results of subtelomeric screening by the Multiplex Ligation Dependent Probe Amplification (MLPA) Technique in 100 selected patients with idiopathic mental retardation (IMR) in Iran.Materials and MethodsA number of 100 patients with IMR, normal karyotypes and negative fragile-X and metabolic tests were screened for subtelomeric abnormalities using MLPA technique.ResultsNine of 100 patients showed subtelomeric abnormalities with at least one of the two MLPA kits. Deletion in a single region was found in 3 patients, and in two different subtelomeric regions in 1 patient. Duplication was only single and was present in 2 patients. Three patients were found to have both a deletion and duplication.MLPA testing in the parental samples of 7 patients which was accessible showed that 4 patients were de novo, 2 patients had inherited from a clinically normal mother, and one had inherited from a clinically normal father. Screening with the two MLPA kits (SALSA P036 and SALSA P070) proved abnormality in only five of the 9 patients.ConclusionsSo, the prevalence rate of abnormal subtelomeres using MLPA technique in patients with idiopathic MR in our study was 5 - 9%, the higher limit referring to the positive results of one of the two MLPA kits, and the lower limit representing the results of positive double-checking with the two MLPA kits.

Genomic characterization of some Iranian children with idiopathic mental retardation using array comparative genomic hybridization.

BACKGROUND:Mental retardation (MR) has a prevalence of 1-3% and genetic causes are present in more than 50% of patients. Chromosomal abnormalities are one of the most common genetic causes of MR and are responsible for 4-28% of mental retardation. However, the smallest loss or gain of material visible by standard cytogenetic is about 4 Mb and for smaller abnormalities, molecular cytogenetic techniques such as array comparative genomic hybridization (array CGH) should be used. It has been shown that 15-25% of idiopathic MR (IMR) has submicroscopic rearrangements detectable by array CGH. In this project, the genomic abnormalities were investigated in 32 MR patients using this technique.MATERIALS AND METHODS:Patients with IMR with dysmorphism were investigated in this study. Karyotype analysis, fragile X and metabolic tests were first carried out on the patients. The copy number variation was then assessed in a total of 32 patients with normal results for the mentioned tests using whole genome oligo array CGH. Multiple ligation probe amplification was carried out as a confirmation test.RESULTS:In total, 19% of the patients showed genomic abnormalities. This is reduced to 12.5% once the two patients with abnormal karyotypes (upon re-evaluation) are removed.CONCLUSION:The array CGH technique increased the detection rate of genomic imbalances in our patients by 12.5%. It is an accurate and reliable method for the determination of genomic imbalances in patients with IMR and dysmorphism.

Microarray-Based Prenatal Diagnosis in Developing Countries

Detection of chromosomal alterations in prenatal diagnosis requires speed and precision, imposing the development of high-throughput screening methods. Thus the array CGH technology, used to diagnose genomic rearrangements in children with multiple congenital anomalies, idiopathic mental retardation and developmental delay, caught the attention of specialists worldwide who are now trying to implement it in routine prenatal practice in order to obtain rapidly useful information for a more accurate genetic counseling. Array comparative genomic hybridisation (Array CGH) has the capacity to detect genomic rearrangements at a higher resolution than other methods used in prenatal testing, like standard G banding, multiplex ligation dependent probe amplification (MLPA) or fluorescent in-situ hybridization (FISH), being able to detect chromosomal imbalances smaller than 3 Mb. Despite all these evidences that prove its utility in prenatal diagnosis, this method is not used worldwide either because of lack of experienced specialists in interpreting array results or because, especially in developing countries, the national health insurance systems does not settle the high cost of this analysis and patients cannot afford it. This paper is a summary of recent progresses made using the array CGH technology in prenatal testing to detect if genomic imbalances are involved in the development of congenital malformations. Our aim is to reveal the importance of using advanced technologies like array CGH in routine prenatal practice, and thus to contribute to its implementation in developing countries like ours.

Multiplex ligation-dependant probe amplification study of children with idiopathic mental retardation in South India

BACKGROUND:Mental retardation (MR) is a heterogeneous dysfunction of the central nervous system exhibiting complex phenotypes and has an estimated prevalence of 1-3% in the general population. However, in about 50% of the children diagnosed with any form of intellectual disability or developmental delay the cause goes undetected contributing to idiopathic intellectual disability.MATERIALS AND METHODS:A total of 122 children with developmental delay/MR were studied to identify the microscopic and submicroscopic chromosome rearrangements by using the conventional cytogenetics and multiplex ligation dependent probe amplification (MLPA) analysis using SALSA MLPA kits from Microbiology Research Centre Holland [MRC] Holland.RESULTS:All the recruited children were selected for this study, after thorough clinical assessment and metaphases prepared were analyzed by using automated karyotyping system. None was found to have chromosomal abnormality; MLPA analysis was carried out in all subjects and identified in 11 (9%) patients.CONCLUSION:Karyotype analysis in combination with MLPA assays for submicroscopic micro-deletions may be recommended for children with idiopathic MR.