Mental Retardation Of Unknown Etiology Research Articles

Clinical studies on submicroscopic subtelomeric rearrangements: a checklist

BACKGROUNDSubmicroscopic subtelomeric chromosome defects have been found in 7.4% of children with moderate to severe mental retardation and in 0.5% of children with mild retardation. Effective clinical preselection is essential...

Isolated adipic aciduria

Adipic acid can appear, in combination with other dicarboxylic acids, in the urine of patients in a number of underlying metabolic diseases. A child with seizures and mental retardation of unknown etiology who was found to have elevated isolated adipic aciduria on investigation for metabolic diseases is reported. A dietary artifact was suspected, and the adipic aciduria resolved after the child was kept on a specific restricted diet for 3 days. This is the third report of isolated adipic aciduria secondary to food. Findings confirm the previous reports of dietary origin of isolated adipic aciduria and should alert clinicians to such artifact before committing patients to unnecessary treatments.

Molecular screening for fragile X syndrome in mentally handicapped children in Korea.

Fragile X syndrome is one of the most common forms of inherited mental retardation and is caused by the expansion of the CGG trinucleotide repeats in the FMR-1 gene. This study was aimed to facilitate the molecular screening of fragile X syndrome in Korean children with mental retardation of unknown etiology. The subjects were tested by Expand Long Template PCR system in the presence of 7-deaza-dGTP, and then by Southern blot analysis. The PCR method provided rapid and reliable results for the identification of fragile X negative and positive patients. One hundred one mentally retarded children (78 males and 23 females) were screened by PCR amplification, which detected only one abnormal sample. The PCR-positive case was confirmed by the CGG repeat expansion on Southern blot analysis with a positive cytogenetic result. In conclusion, Expand Long Template PCR may be used as the first screening test for detecting the fragile X syndrome.

FRAXA screening in Brazilian institutionalized individuals with nonspecific severe mental retardation.

Individuals with mental disabilities are a heterogeneous group, mainly when we consider the etiology of mental retardation (MR). Recent advances in molecular genetics techniques have enabled us to unveil more about the molecular basis of several genetic syndromes associated with MR. In this study, we surveyed 85 institutionalized individuals with severe MR, 38 males and 47 females, by two molecular techniques, to detect CGG amplifications in the FMR1 gene. No FRAXA mutations were found in the FMR1 gene, reinforcing the low prevalence of Fragile X syndrome among institutionalized individuals with severe MR. We considered the PCR protocol used adequate for screening males with mental retardation of unknown etiology. The use of the Southern blot is still necessary for the decisive diagnosis of the Fragile X syndrome. To exclude chromosomal abnormalities associated with MR as a possible cause of the phenotype in these individuals, G-banded chromosome analysis was performed in all patients and 7.3% of chromosomal aberrations were found. Our results are similar to those reported previously and point to the necessity of expanding the molecular investigation toward other causes of MR, such as subtle chromosomal rearrangements, as suggested recent by a combination of fluorescence in situ hybridization (FISH) and PCR studies.

Clinical characteristics of children with mental retardation of unknown etiology in Korea.

The purpose of this study was to investigate the clinical characteristics of children with mental retardation (MR) of unknown etiology for early recognition and intervention. In this study, we defined children with MR of unknown etiology as those without clear etiologies for MR despite extensive evaluation and were not associated with pathological behavioral problems such as pervasive developmental disorders and attention-deficit/hyperactivity disorder. The clinical characteristics of children with MR of unknown etiology were as follows. 1) MR of unknown etiology was 48.8% of all MR. 2) MR of unknown etiology was more common in males. 3) Delayed language development was a leading factor that made the parents of children with MR of unknown etiology seek help from physicians. However, most of the children with MR of unknown etiology showed a relatively uniform delay in several areas of development. 4) Most children with MR of unknown etiology were delayed walkers. 5) Most children with MR of unknown etiology were mild cases.

Brief report: gaze behavior and theory of mind abilities in individuals with autism, down syndrome, and mental retardation of unknown etiology.

Brief report: gaze behavior and theory of mind abilities in individuals with autism, down syndrome, and mental retardation of unknown etiology.

Fast‐wave periodic complexes in a mentally retarded child who later developed subacute sclerosing panencephalitis: a modification of a classic EEG by preexisting brain damage?

The EEG of a 12-year-old girl with stage II subacute sclerosing panencephalitis (SSPE), who had also suffered from a non-progressive mental retardation of unknown aetiology since early childhood, revealed periodic generalised stereotyped fast wave bursts synchronous with myoclonic jerks. The background activity was nearly normal. The diagnosis of SSPE was established by raised serum and measles antibody titres, raised CSF IgG, and brain biopsy. This rare type of periodic complex has only once been described in the literature, again in a mentally retarded child who had developed SSPE. We suggest a mechanism of origin of this type of periodic complex drawn from observations in these two cases, and discuss its significance.

Linguistic and cognitive ability of adults with Down syndrome and mental retardation of unknown etiology

The linguistic and cognitive abilities of adults with Down syndrome were compared to those of adults with mental retardation of unknown etiology matched for mental and chronological age. Linguistic data consisted of verbal responses to an elicitation procedure that tested for forty-three different linguistic constructions. Cognitive tests measured simultaneous, successive, auditory, and visual processing. The adults with Down syndrome exhibited significantly poorer linguistic ability than the adults with mental retardation of unknown etiology. Though the two groups exhibited different cognitive profiles, differences in cognitive abilities could not account for the difference in linguistic ability.

Females with fragile X syndrome: A review of the effects of an abnormal FMR1 gene

AbstractIn 1980, Turner et al. described a sample of females affected with fragile X syndrome and recommended that all females with mental retardation of unknown etiology be evaluated for this condition. Since then, much has been learned about fragile X syndrome and its effects on females. Although research has primarily focused on abnormal cognitive and emotional findings in a proportion of women, studies have also addressed the physical characteristics and specific findings of young girls. Some of the early results were puzzling because so little was understood about the genetics of this condition, but much has become clear since the gene was sequenced in 1991. Many questions about this condition are still unanswered, but are likely to be addressed in the near future. This article highlights major advances made during the past 10 years with regard to females having fragile X syndrome. © 1995 Wiley‐Liss, Inc.

Etiologic and pathogenetic study of mental retardation with multiple congenital anomalies.

Etiology and pathogenesis of MCA/MR in 1,023 patients (618 male; 405 female) with mental retardation were studied. Of 1,023 patients, there were 563 cases (317 male; 246 female) with MCA (55%). Among the MCA patients, there were 303 (156 male; 147 female) whose primary etiology was clarified (53.8%). Among the 260 patients with MCA/MR of unknown etiology, there were 23 with recognizable syndromes of unknown etiology and 7 previously reported by us as possibly having a new malformation syndrome. We had 569 patients with mental retardation of unknown etiology including 263 (41.5%) who were involved with MCA.

Martin-Bell syndrome in Greece, with report of another 47,XXY fragile X patient.

A cytogenetic investigation was carried out among 200 mentally retarded boys in Greece for the detection of the fragile X [fra(X)] syndrome. Thirteen patients were found to carry fra(X) (6.5%). Of those, six boys had a history of familial X-linked mental retardation, two had the phenotype of the Martin-Bell syndrome, four had only mental retardation of unknown etiology, and one was a mentally retarded patient with Klinefelter syndrome. The remaining 187 boys were fra(X) negative. Our findings emphasize the importance of early identification of this syndrome in the diagnosis and prevention, through proper genetic counselling, of mental retardation.

Increased blood lead levels in mentally retarded children in Greece.

In 60 children with mental retardation of unknown etiology, the whole blood lead, as well as the activity of the red cell delta-aminolevulinic acid dehydratase (delta-ALAD), was measured. Thirty normal children and 30 with mental retardation of known etiology were used as controls. The lead values were found significantly higher in the study patients compared with both control groups (P less than 0.001). The delta-ALAD activity in the 14 patients with blood lead levels greater than or equal to 40 microgram/dl, was significantly reduced compared with the normal controls (P less than 0.001) and the mentally retarded controls (P less than 0.01). In more than 20% of the patients with mental retardation of unknown etiology, indications of significant exposure to lead were found. There was no difference in blood lead values between children from cities and those from rural areas. The possible role of lead in the etiology of mental retardation is discussed.

Variant chromosome 3 (inv3) in normal newborns and their parents, and in children with mental retardation.

The chromosomes of 102 normal newborn babies (51 boys and 51 girls) born at term, their parents, and 45 nonrelated children with mental retardation at the level of imbecility were investigated by fluorescence microscopy using propyl quinacrine mustard. In each of the 11 families, one of the parents had a variant chromosome 3 that was interpreted as resulting from a pericentric inversion of the brilliant band (or C band) only (inv3). In four cases inv3 was transmitted to the child. The frequency of inv3 in newborn boys and girls was 2 and 6% respectively, and in adult men and women 5 and 6% respectively. In children with mental retardation of unknown etiology the inv3 was detected in five cases (11.1%). This difference from normal persons was not significant.

Pathologic axons and synapses in human neuropsychiatric disorders

Ultrastructural studies of cerebral biopsy specimens from patients with various forms of psychomotor retardation and dementia have disclosed pathologic changes in axons and presynaptic or postsynaptic processes. The clinical disorders with lesions in axons and presynaptic terminals are reviewed. Three basic abnormalities have been detected: proliferation of tubulovesicular structures, which probably originate from the smooth endoplasmic reticulum, “abnormal” mitochondria, and proliferation of 80 to 100filaments. Understanding of the pathogenesis of human disorders associated with axonic or “synaptic” lesions will probably depend on progress in areas of basic biomedical research concerned with the synthesis and turnover of biological membranes and the packaging and secretion of neurotransmitters, elucidation of mechanisms of cytoplasmic streaming and axoplasmic flow, and biophysical and biochemical characteristics and functions of “fibrous” proteins (neurotubules, neurofilaments, pathologic fibrous proteins). In several cases of mental retardation of unknown etiology, abnormal dendritic spines of cortical neurons have been observed with the use of the Golgi method. These dendritic (postsynaptic) disorders have been attributed to defective development (“dysgenesis”). The knowledge provided by ultrastructural analysis of brain tissue from the human disorders of mental retardation or dementia is “still formless, incomplete, lacking the essential threads of connection,” 55 and only future developments in basic neurobiology will make possible the dissection of the primary phenomena from the secondary and probably irrelevant findings.

Dendritic Spine "Dysgenesis" and Mental Retardation

Golgi studies reveal abnormally long, thin spines and the absence of short, thick spines on dendrites of cortical neurons in retarded children with normal karyotypes. The degree of dendritic spine loss and abnormality appears to be related to age and the severity of developmental retardation. Dendritic spine "dysgenesis" is a common feature of the microstructural pathology that occurs in profound mental retardation of unknown etiology.