Cause Of Mental Retardation Research Articles

Analytical and Clinical Performance of a Real-time Screening PCR Assay Identifying Congenital CMV Infection

BackgroundCongenital CMV infection (cCMV) is the most common identifiable cause of mental retardation in the United States but requires early diagnosis to define the infection and to institute effective antiviral therapy. Traditional identification strategies including hearing screens and physical exams likely miss many patients with cCMV. We therefore developed and evaluated the performance of a PCR assay optimized for low cost, specimen collection at time of dried blood spot collection, and detection thresholds below the salivary CMV concentrations known to occur in cCMV patients.MethodsWe utilized a real-time CMV PCR assay (SimplexaTM CMV)(DiaSorin, Cypress CA) amplifying the UL83 gene and the 3M Integrated Cycler. Saliva was collected from volunteers (Copan swab), and spiked with known concentrations of CMV culture supernatant quantified by COBAS AmpliprepTM. (Roche Diagnostics). Additionally, saliva was collected by copan swab from all births within a single multi-hospital system from 3/21/16 – 5/4/17. Newborns who were initial screen PCR positive were subsequently evaluated by urine CMV PCR by an outside laboratory for confirmation of cCMV.ResultsAnalytical threshold of detection was well below 4 log copies/ML, with 100% of samples testing positive at 3.5 log copies/ML (Fig 1). 6127 newborn saliva samples were evaluated and 61 were PCR positive (£40 CT). 47 of these tests were confirmed by urine PCR (Fig 2) (PPV 0.9792, NPV 0.9988, Sens 0.8704, Spec 0.9998). Screen positive tests which were not confirmed by urine PCR had CT values £36. Adjusting the definition of a positive to CT £36 further improved the performance (PPV >0.9999, NPV 0.9997, Sens 0.9592, Spec >0.9999).ConclusionWe demonstrate good performance of a congenital CMV methodology thus facilitating an effective universal newborn screening programDisclosures J. P. Devincenzo, AstraZeneca/MedImmune: Investigator, Research support

Mental Retardation in Children, Causes &Prevention

This study was conducted to know the definite & probable causes of mental retardation (M.R.) in children & how can we prevent some of the cases. Three hundred eighty three children with moderate to severe (M.R.) were studied in Kerbala Pediatric Hospital over two years from January 2003 to January 2005. The male to female ratio was 1.51:1. The etiology was known in151 patients (39.4%) & was unknown in 232 patients (60.6%). The probable preventable causes include kernicterus, hypoxic ischaemic encephalopathy, severe malnutrition, prematurity neonatal sepsis, hypothyroidism, encephalitis, meningitis, neural tube defect, galactossaemia, shaken baby syndrome & lead poisoning, constituting (68.8%) of the known probable causes. There was a high rate of consanguinity of parents, (37.8%) were first cousin, (24.8%) wer relatives while (37.4%) were not related. Three hundred forty eight patients (90.88%) were diagnosed before their first birthday. It was concluded from the study that we can help to reduce cases of (M.R.) by practicing primary & secondary prevention through health promotion, specific protection; early diagnosis & treatment of treatable disorders by neonatal screening program.

Dysphagia in Rett Syndrome: A Descriptive Study.

Rett syndrome (RS) is a neurodevelopmental disorder and the second major cause of mental retardation in females. The aim of this study was to evaluate swallowing problems of RS patients by endoscopic assessment and compile a list of suggestions for managing feeding and preventing complications. The sample consisted of 61 female patients (mean age = 13.6 years, range, 2-33 years) admitted to the Department of Neuropsychiatry, where they had previously been diagnosed with RS. Speech evaluation associated with observation during mealtimes was useful to formulate suggestions for caregivers. Progressive deterioration of feeding was commonly noted by caregivers. Fifty-four patients had a history of recurrent episodes of bronchitis. Oral apraxia, dyskinetic tongue movements, prolonged oral stage, and poor bolus formation were the most common findings in all patients. Dysphagia was primarily limited to oral preparatory phases, while the pharyngeal phase was normal in most patients. The high percentage of dysphagia suggests the need to accurately monitor the feeding capability of RS children. It is critical to correctly inform caregivers about safe swallowing procedures to reduce the incidence of fatal complications.

Comprehensive Analyses of Molecules with Altered Expression in the Brain of a Mouse Model of Down Syndrome for Identification of Pharmacotherapeutic Targets.

Down syndrome, caused by the triplication of human chromosome 21, is the most frequent genetic cause of mental retardation. Mice with a segmental trisomy for mouse chromosome 16, which is orthologous to human chromosome 21, exhibit abnormalities similar to those in individuals with Down syndrome and therefore offer the opportunity for a genotype-phenotype correlation. In the current review, I present several mouse lines with trisomic regions of various lengths and discuss their usefulness for elucidating the mechanisms underlying Down syndrome-associated developmental cognitive disabilities. In addition, our recent comprehensive study attempting to identify molecules with disturbed expression in the brain of a mouse model of Down syndrome in order to develop a pharmacologic therapy for Down syndrome is described.

Etiological evaluation of primary congenital hypothyroidism cases.

Primary congenital hypothyroidism is frequently seen endocrine disorder and one of the preventable cause of mental retardation. Aim of study was to evaluate the frequency of permanent/transient hypothyrodism, and to detect underlying reason to identfy any marker which carries potential to discriminate permanent/transient form. Forty eight cases older than 3 years of age, diagnosed as primary congenital hypothyroidism and started thyroxin therapy in newborn-period, and followed up between January 2007-June 2013 were included in the study. Thyroid hormon levels were evaluated and thyroid ultrasonography was performed in cases who are at the end of their 3 years of age, after 6 weeks of thyroxine free period. Thyroid sintigraphy was performed if serum thyroid-stimulating hormone was high (≥ 5 mIU/mL) and perchlorate discharge test was performed if uptake was normal or increased on sintigraphy. Cases with thyroid-stimulating hormone levels ≥ 5 mIU/mL were defined as permanent primary congenital hypothyroidism group and as transient primary congenital hypothyroidism group with normal thyroid hormones during 6 months. The mean age was 3.8±0.7 years. Mean diagnosis age was 16.6±6.5 days and 14 cases (29.2%) were diagnosed by screening program of Ministry of Health. There were 23 cases (14F, 9M) in permanent primary congenital hypothyroidism group and 12 (52.2%) of them were dysgenesis (8 hypoplasia, 4 ectopia), and 11 (47.8%) dyshormonogenesis. In transient primary congenital hypothyroidism group, there were 25 cases (17M, 8F). The mean thyroid-stimulating hormone levels at diagnosis were similar in two groups. The mean thyroxin dose in permanent primary congenital hypothyroidism group was significantly higher than transient group at the time of thyroxin cessation (2.1±0.7, 1.5±0.5 mg/kg/d, respectively, p=0.004). Thyroxin dose ≥1.6 mcg/kg/d was 72% sensitive and 69.6% specific for predicting permenant primary congenital hypothyroidism. Transient primary congenital hypothyroidism is more frequent than expected and found often in males in the primary congenital hypothyroidism cases, started thyroxin therapy in neonatal period. While fT4, thyroid-stimulating hormone, Tg levels at diagnosis do not predict transient/permenant primary congenital hypothyroidism, thyroxin dose before the therapy cessation at the age of 3 may make the distinction between transient/permenant primary congenital hypothyroidism.

Evaluation of Craniofacial Morphology in Subjects with Down’s Syndrome: A Cephalometric Study

<p><em><strong>D</strong>own’s syndrome is a disease entity in which the defect in mental development is associated in a unique way with a large number of physical defects. It is a condition resulting from an extra chromosome 21 and thus the condition is also known as Trisomy 21. It is considered one of the most frequent genetic causes of mental retardation.</em></p><p><em>The incidence of Down’s syndrome is estimated to be between 1.6 to 2.5 per 1000 live births and increases with increase in maternal age.<sup>4,59,10</sup> Mongoloids usually exhibit retarded motor and language skills, with an IQ range from extremely low to 45-55.</em></p><p><em>Cephalometry has now been firmly established as the most essential procedure for gaining knowledge of the complexities of dentofacial skeletal pattern. By utilizing cephalometric radiography, whereby description, morphologic outline, measurement and change in growth of the skull can be fairly accurately ascertained, it might be possible to observe some of the subtle</em></p><em>The present study is an attempt to determine cephalometrically whether the group of individuals with Down’s syndrome have a distinctive craniofacial phenotype. The growth of the craniofacial area in the presence of the extra chromosome is also examined.</em>

The physiological phosphorylation of tau is critically changed in fetal brains of individuals with Down syndrome.

Down syndrome (DS) is a common cause of mental retardation accompanied by cognitive impairment. Comprehensive studies suggested a link between development and ageing, as nearly all individuals with DS develop Alzheimer disease (AD)-like pathology. However, there is still a paucity of data on tau in early DS to support this notion. Using morphometric immunohistochemistry we compared tau phosphorylation in normal brains and in brains of individuals with DS from early development until early postnatal life. We observed in DS a critical loss of physiological phosphorylation of tau. Rhombencephalic structures showed prominent differences between controls and DS using antibodies AT8 (Ser-202/Thr-205) and AT180 (Thr-231). In contrast, in the subiculum only a small portion of controls deviated from DS using antibodies AT100 (Thr-212/Ser-214) and AT270 (Thr-181). With exception of the subiculum, phosphorylation-independent tau did not differ between groups, as confirmed by immunostaining for the HT-7 antibody (epitope between 159 and 163 of the human tau) as well. Our observations suggest functional tau disturbance in DS brains during development, rather than axonal loss. This supports the role of tau as a further important player in the pathophysiology of cognitive impairment in DS and related AD.

Socioeconomic Determinants Affecting Compliance to therapy in Patients with Congenital Hypothyroidism in Sharkia Governorate

Background: Congenital hypothyroidism (CH) is the most common preventable causes of mental retardation in children thus compliance to medication is known to improve the neurodevelopmental outcomes. Compliance to therapy can be affected by multiple factors. Objectives: The study aimed to explore compliance of the patients' guardian to medical therapy and to explore the socioeconomic factors affecting compliance to medication in patients with CH. Methods: A cohort follow-up study was conducted in Endocrinology and Pediatric Outpatient Clinics in Sharkia Governorate health insurance center. The study participants were 120 newborn and infant with CH. Data were collected using multi-structured questionnaires for determining socioeconomic state and Morisky Medication Adherence Scale (MMAS 8) to assess patient compliance. The results of investigations at diagnosis (initial TSH and T4) and during the follow-up visits were reviewed. Results: About two third of patient families were highly compliant to therapy. Compliance to therapy was affected by the occupational and educational levels of the parents as well as residence, income, social class of the parents and presence of symptoms and associated congenital anomalies. But the most significant factors affecting compliance to therapy were mother's education, social class, and the presence of symptoms at presentation.Conclusion: Compliance with L-thyroxin therapy in our patients and/or their family was found to be reasonable. The most significant factors affecting the compliance were mother's education, social class, and the presence of symptoms at presentation.

The Study on the Psycho-social Issues and Challenges of Children with Mental Retardation: A Case Study

A lot has been written about the psycho-social issues and challenges of children with mental retardation. The aim of this research is to investigate the impact of psycho-social issues and challenges of children with mental retardation. The study utilized qualitative research tools to explore the deep feelings of the participants. Purposive sampling technique and case study employed as a major study tools. The study used in-depth interview, observation and FGD. The collected data were organized and analyzed through qualitative research approach by using thematic analysis. Findings obtained from the study showed that children with mental retardation are facing different psychosocial challenges like stigma, discrimination, isolation, blame, shame, frustration, feeling of upset, self-insult, loneliness, losing respect, despairing (feeling of no hope), insult, anger and sadness. The study also found that the perception parents of children with mental retardation regarding the causes of retardation was changed from religious beliefs to possible causes of mental retardation as a result of the rehabilitation services. Further, praying, helping each other, reaction formation (insulting who insulted them), developing wishful thinking, and limiting one's interaction were some of the mechanisms explored from this study. The study finally concludes some measures to curb the negative belief systems of the communities towards the children with mental retardation. The study has a great implication for social work practice in the area of policy formulation, advocacy, community mobilization, empowerment, service provision, assessment and research in the areas of disability.

Intellectual development in preschool children with early treated congenital hypothyroidism

PurposeDelayed treatment of congenital hypothyroidism (CH) is a common cause of mental retardation. The aim of the present study was to evaluate intellectual outcomes in preschool children with treated CH.MethodsWe retrospectively reviewed the clinical records of 43 children (age range: 13 to 60 days of life; 22 girls and 21 boys) diagnosed with CH. Children aged 5 to 7 years were examined using the Korean Wechsler Intelligence Scale for Children or the Korean Wechsler Preschool and Primary Scale of Intelligence.ResultsThe patients started treatment between 13 and 60 days of age. The mean intelligence quotient (IQ) of patients tested at age 5 to 7 years was 103.14±11.68 (IQ range: 76–126). None had intellectual disability (defined as an IQ <70). Twenty-one subjects were treated with a low dose (6.0–9.9 µg/kg/day) and 22 with a high dose of levothyroxine (10.0–16.0 µg/kg/day). There was no significant difference in the mean full-scale IQ (FSIQ), verbal IQ (VIQ), and performance IQ (PIQ) scores between the 2 groups. FSIQ, PIQ, and VIQ scores were not significantly correlated with initial dose of L-T4, initial fT4, age at treatment in multivariate analysis.ConclusionIQ scores of subjects with early treated CH diagnosed through a neonatal screening test were within normal range, regardless of etiology, thyroid function, initial dose of levothyroxine, and age at start of treatment.

Toxicity and Viral Load in Urine during Valganciclovir Therapy in Premature Infants

Cytomegalovirus (CMV) infection is the most important cause of mental retardation and sensorineural hearing loss. Antiviral treatment with valganciclovir, a relatively new but potential toxic oral drug, is recommended to prevent further hearing deterioration. In this retrospective cohort study we evaluated the relation between the dose of valganciclovir and the reduction of CMV viral load, as well as the toxicity. All neonates with gestational age

The diagnostic impact generated by the presence of Cytomegalovirus IgM antibodies in pregnancy

Background: Cytomegalovirus (CMV) infection is one of the most common congenital infections and the most frequent cause of mental retardation and non-genetically cause of deafness. The risk of fetal transmission is above 40%. The objectives of this study were to review and improve the CMV diagnosis in pregnancy. Method: 50 pregnant women took part in the study. They were taken in evidence at the virology counseling office. The reason for the need of viral diagnosis came from the fact that the result of previous routine serological testing came out positive for CMV IgM antibodies (Ab). Based on the test result, the gynecologist may normally indicate the termination of the pregnancy. Results: In the virology counseling office the results for CMV IgM Ab test turn out negative in 48 of the 50 (96%) referred pregnant women. In two women CMV IgM Ab test turn out positive. These women also tested positive for CMV IgG Ab test. The pregnant women were also tested for pp65 antigenemia. They presented a four times raise in CMV IgG Ab titer. All the rest were negative for pp65 antigemenia. Conclusion: From the 50 women only two needed to terminate their pregnancies. It is important to test for CMV infection in pregnancy along with other viral, bacterial or parasitic infections, but the indication of pregnancy termination must be taken only after a thorough examination and testing. It would be helpful if CMV tests, as well as all the TORCH tests were supported by the health insurance system.

Clinical approach to congenital hypothyroidism

Congenital hypothyroidism (CH) is a preventable cause of mental retardation. The principal causes include thyroid dysgenesis and dyshormonogenesis. Central CH is rare. Due to absence of overt symptoms at birth, diagnosis is often delayed. There are some known syndromic associations with extrathyroidal anomalies. Neonatal screening programs help in early detection and categorization of cases requiring immediate treatment or close follow-up. Results of screening tests could guide further tests required for confirmation diagnosis and urgency of replacement therapy. A diagnostic protocol starting with an ultrasonography of thyroid and serum thyroglobulin levels can aid identify the probable underlying etiology and dictate the cases requiring scintigraphy or genetic tests. Early initiation of treatment with oral levothyroxine improves neurocognitive outcomes. Some cases might have transient hypothyroidism and reevaluation at 3 years of age may help in further discontinuation of treatment.

Impact of compliance to therapy of congenital hypothyroidism on the neurodevelopmental outcome in Sharkia Governorate

Objective The objective of this study was to evaluate the compliance to congenital hypothyroidism (CH) therapy and the effect of noncompliance on the physical and mental development. Background CH is the most common preventable cause of mental retardation in children. Early treatment and high compliance are important prognostic factors for mental and physical development in children with CH. Patients and methods A prospective study design was conducted in the Endocrinology Outpatient Clinics in Sharkia Governorate health insurance center. The participants were 120 newborns and infants with CH and their mothers (patients), and 120 age-matched volunteers of healthy infants and children and their mothers (control). Data were collected using multistructured questionnaires for determining the socioeconomic state, clinical picture, personal, family and obstetric history, and Morisky Medication Adherence Scale (MMAS 8) to assess compliance. Assessment of physical growth was carried out through anthropometric measurements and assessment of mental development was conducted using Vineland-II scale for infants below 2 years and using Stanford–Binet 5 Intelligence scales for individuals of 2 years and older. Review of the results of investigations at diagnosis and during the follow-up visits are provided. Results Two-thirds of the patient families were highly compliant. There was a very high significant difference between different compliance grades and between patients and control groups as regards the parameters of mental and physical development. No significant difference was found between the highly compliant cases and control. Conclusion Compliance to therapy in our patients and/or their family was reasonable. High compliance to treatment was an important prognostic factor for normal mental and physical development in patients with CH.

Congenital hypothyroidism - An Indian perspective

Congenital hypothyroidism (CH) is a preventable cause of mental retardation in neonates. In India, CH is compounded by a lack of efficient newborn screening (NBS) programs, nonavailability of infrastructure, and the rising cost of health care. This review focuses on NBS techniques for early detection of CH, along with management strategies in the Indian scenario. Guidelines recommend measuring thyroid-stimulating hormone (TSH) or thyroxine (T4) levels or combined TSH and T4 as an ideal approach for screening CH within 2–4 days after birth. In preterm and low birth weight neonates, additionally, after 2–4 weeks, a follow-up screening has been suggested. If laboratory test is positive, a noninvasive scintigraphy and/or ultrasound has also been suggested as additional test to identify underlying etiology. Levo-T4 (L-T4) has been recommended as the first-line treatment with an initial standard dose of 10–15 μg/kg/day, based on the disease severity; with regular follow-up, up to 3 years of age. Although L-T4 tablet form is the standard of care in many developing countries like India, liquid formulations of L-T4 have been found to possess some additional beneficial effects. In summary, the government or policymakers should encourage mandatory cost-effective NBS for the early detection and treatment of CH.

The role of season and climate in the incidence of congenital hypothyroidism in Kerman province, Southeastern Iran.

Congenital hypothyroidism (CH) is a common endocrine disease and an important cause of mental retardation. The purpose of this study was to investigate the probable role of season and climatic factors in the incidence of CH in Kerman province, Iran. Incidence data were collected from the CH screening program files from 2005 to 2011 in Kerman province, a number of 288,437 infants were included in the study. Climate data were collected from the Meteorological Office. The relations were tested by χ2-test, Pearson correlation, and negative binomial regression. The overall incidence of CH in Kerman province was 2.68 per 1000 births. There was a significant difference in both the monthly and seasonal incidence of CH (p<0.05). There were a few significant, but weak correlation between some climatic factors and the incidence of CH in some regions, but the results were inconsistent. It seems like there is no clear relation between CH incidence and climate factors, in Kerman Province. However, CH incidence was highest in October (Autumn) and lowest in June (Summer).

Permanent and Transient Congenital Hypothyroidism in Hamadan West Province of Iran.

BackgroundPrimary congenital hypothyroidism (CH) is the most common treatable cause of mental retardation and can be classified into permanent and transient types. The purpose of this study was to determine the prevalence of permanent and transient congenital hypothyroidism (CH) in Hamadan, West province of Iran.MethodsThe study population included all cases with primary congenital hypothyroidism, which were confirmed by thyroid function tests (TSH levels ≥ 10 mIU/L). All these patients had been followed up at the outpatient pediatric endocrine clinic of Besat hospital (Hamadan, Iran) for a period of time between May 2006 and March 2013. Biochemical findings at diagnosis and detailed medical records were collected. Patients were considered as permanent hypothyroidism if their TSH level was 10 (mIU/l) during 6 - 12 months of treatment. Also three years old patients with TSH level > 10 mU/L during one or three months after discontinuation of levothyroxine treatment were considered as permanent hypothyroidism.ResultsA total of 164 children (49.9% male and 50.6% female) diagnosed with CH completed the study. Female/male ratio was 1.02/1. The incidence of CH was about 1/1250 in Hamadan, West province of Iran. Of the 164 patients, 105 cases (64 %) were diagnosed as permanent CH and other 59 cases (36%) were proven to have transient hypothyroidism. Female to male ratio was 1.14 in patients suffering from permanent CH and 0.8 in patients with transient CH. The initial TSH level was found to be significantly higher in cases with permanent CH compared to the patients with transient CH (P = 0.001). Mean TSH level during the first year of treatment was higher in permanent CH cases compared to transient cases (P = 0.001). Children with transient CH had a lower TSH serum level during the three years of treatment (P = 0.000). A significant statistical difference was not found between the genders and permanent or transient CH (P = 0.352). Co-occurring congenital anomalies and birth order were significantly different between two groups (P = 0.028 and P = 0.024, respectively).ConclusionsOur regional follow-up data showed that about 40% of newborns with primary CH had transient thyroid dysfunction. Our results further clarify our previous research by providing evidences on the incidence rate of CH. The incidence rates of CH as well as transient type of CH in our region were higher than those reported by other studies which have been conducted in other regions of the world. The initial TSH level was the strongest predictor of treatment cessation. Given the high incidence of transient CH in our region, further studies are needed to confirm the etiology and to provide considerable insight into preventive and/or the treatment strategies.

CONGENITAL HYPOTHYROIDISM

Congenital hypothyroidism (CH) is the most common congenital endocrine disorder whose incidence in newborns is 1:2,000 to 1:4,000. It is the leading cause of mental retardation. Neonatal Screening Programs make it possible to identify the disease at an early stage and to start the adequate therapy of the children, thanks to which it is possible to avoid complications related to the hormone deficiency.

Molecular Characterization of Down Syndrome Embryonic Stem Cells Reveals a Role for RUNX1 in Neural Differentiation.

SummaryDown syndrome (DS) is the leading genetic cause of mental retardation and is caused by a third copy of human chromosome 21. The different pathologies of DS involve many tissues with a distinct array of neural phenotypes. Here we characterize embryonic stem cell lines with DS (DS-ESCs), and focus on the neural aspects of the disease. Our results show that neural progenitor cells (NPCs) differentiated from five independent DS-ESC lines display increased apoptosis and downregulation of forehead developmental genes. Analysis of differentially expressed genes suggested RUNX1 as a key transcription regulator in DS-NPCs. Using genome editing we were able to disrupt all three copies of RUNX1 in DS-ESCs, leading to downregulation of several RUNX1 target developmental genes accompanied by reduced apoptosis and neuron migration. Our work sheds light on the role of RUNX1 and the importance of dosage balance in the development of neural phenotypes in DS.

The Role of Season and Climate in the Incidence of Congenital Hypothyroidism in Kerman Province, Southeastern Iran

Objective: Congenital hypothyroidism (CH) is a common endocrine disease and an important cause of mental retardation. The purpose of this study was to investigate the probable role of season and climatic factors in the incidence of CH in Kerman Province, Iran which has various climates. Methods: Incidence data were collected from the CH screening program files from 2005 – 2011 in Kerman Province, Iran. Climate data was collected from the Kerman Province Meteorological Office. Data were analyzed using R version 3.0.2 and Minitab16 soft wares. The relations were tested by Negative binomial Regression and time series trend analysis. Results: The overall incidence of CH in Kerman was 2.7 per 1000 births. A similar pattern between CH incidence and temperature, humidity and rainfall was not observed in different cities with different climates. Changes in the incidence of hypothyroidism fitted a quadratic trend time series model. It is expected that the incidence of CH declines in the next 10 years. Conclusions: It seems like there is no relation between CH incidence and climate factors. Other world studies have not confirmed a specific pattern either.