Chromosomal variants in mentally retarded and normal men

The possible phenotypic effect of chromosomal variants is as yet an unsolved problem. QM- and C-banded chromosomes of 100 male patients with idiopathic mental retardation were compared with chromosomes of 100 Royal Military College cadets, as controls. Increased size of 9qh seems to be a factor with possible negative effects. 9qh- was found to be more common in the control sample. Another variant found more often in the retarded subjects was 16qh-. Increased frequencies of Yq+ or small inversions in chromosomes 3 and 9 were not found in the retarded.     

Array-CGH detection of micro rearrangements in mentally retarded individuals: clinical significance of imbalances present both in affected children and normal parents

Background

The underlying causes of mental retardation remain unknown in about half the cases. Recent array‐CGH studies demonstrated cryptic imbalances in about 25% of patients previously thought to be chromosomally normal.

Objective and methods

Array‐CGH with approximately 3500 large insert clones spaced at ∼1 Mb intervals was used to investigate DNA copy number changes in 81 mentally impaired individuals.

Results

Imbalances never observed in control chromosomes were detected in 20 patients (25%): seven were de novo, nine were inherited, and four could not have their origin determined. Six other alterations detected by array were disregarded because they were shown by FISH either to hybridise to both homologues similarly in a presumptive deletion (one case) or to involve clones that hybridised to multiple sites (five cases). All de novo imbalances were assumed to be causally related to the abnormal phenotypes. Among the others, a causal relation between the rearrangements and an aberrant phenotype could be inferred in six cases, including two imbalances of the X chromosome, where the associated clinical features segregated as X linked recessive traits.

Conclusions

In all, 13 of 81 patients (16%) were found to have chromosomal imbalances probably related to their clinical features. The clinical significance of the seven remaining imbalances remains unclear. The limited ability to differentiate between inherited copy number variations which cause abnormal phenotypes and rare variants unrelated to clinical alterations currently constitutes a limitation in the use of CGH‐microarray for guiding genetic counselling.     

提重辨别实验中精神发育迟滞儿童的反应特征

采用提重辨别实验对精神发育迟滞儿童(MR)和正常儿童进行了测试比较。结果表明,MR 儿童左手、右手和双手测试成绩间虽未产生显著性差异,但此三种测试条件下的辨别能力明显低于正常儿童。提示其大脑两半球认知功能存有缺陷,不支持国外 MR 儿童认知功能障碍的“左脑障碍”或“右脑障碍”假说。测试中 MR 儿童有明显的不肯定判断倾向,似可作为 MR 儿童高层认知结构的特性反应。     

Cardiovascular and electrodermal responses to simple stimuli in autistic,retarded and normal children

Phasic changes in respiratory period, electrodermal activity (EDA), the evoked cardiac response (ECR), and the vasoconstrictive pheripheral pulse amplitude response (PPAR), were examined in matched groups of autistic, retarded, and normal children, using repeated presentation of simple visual and auditory stimuli. Analysis as a function of group membership and age indicated that respiratory pause and EDA showed habituation in the retarded and normal groups, but not in the autistic group, with no age effects in any group. PPAR and ECR showed no habituation in any group, but within-group age differences, and a higher mean response level for the autistic subjects. The autistic children did not display the diminution of response level with increased age that was characteristic of both the control groups. These effects were obtained across both modalities. Results could not be attributed to between-group tonic cardiac arousal differences, and were interpreted as further indications of diminished sensitivity to reductions in stimulus novelty, as well as developmental delay, in early-onset psychosis.     

Comparative genomic hybridisation in mentally retarded patients with dysmorphic features and a normal karyotype

Segmental aneusomy for small chromosomal regions has been shown to be a common cause of mental retardation and multiple congenital anomalies. A screening method for such chromosome aberrations that are not detected using standard cytogenetic techniques is needed. Recent studies have focused on detection of subtle terminal chromosome aberrations using subtelomeric probes. This approach however excludes significant regions of the genome where submicroscopic rearrangements are also liable to occur. The aim of the present study was to evaluate the efficiency of comparative genomic hybridisation (CGH) for screening of submicroscopic chromosomal rearrangements. CGH was performed in a cohort of 17 patients (14 families) with mental retardation, dysmorphic features and a normal karyotype. Five subtle unbalanced rearrangements were identified in 7 patients. Subsequent FISH studies confirmed these results. Although no interstitial submicroscopic rearrangement was detected in this small series, the study emphasises the value of CGH as a screening approach to detect subtle chromosome rearrangements in mentally retarded patients with dysmorphic features and a normal karyotype.     

96名精神发育迟滞儿童的儿童适应行为评定量表试测报告

本文对96例精神发育迟滞儿童(以下称弱智儿童)采用儿童适应行为评定量表和韦氏智力量表进行了测试,发现该组儿童适应行为评定成绩随年龄增长,但发展水平普遍低于正常儿童,尤以认知应用技能缺损明显。适应行为评定量表与韦氏智测结果具有密切相关,并有较好的临床实证效度。提示该评定量表可作为弱智儿童智力评估的辅助方法。     

A simplified test to detect PKU heterozygotes by discriminant analysis in mentally retarded children and their mothers

We have developed classification coefficients and an equation to detect heterozygotes for phenylketonuria. The combination of several variables (Phe, Phe/Tyr, Phe2/Tyr) gave a safe diagnosis in more than 96% of cases. We then computerized a random selection of our population, which was divided into two groups: the first was "selected" to compute discriminant functions, while the second, excluded from computation, was used to check the fitness of our method. Despite the reduction of sample size, 95.2% of unknown subjects were correctly classified. Finally, we used our equation to detect heterozygotes for phenylketonuria in a population of 26 children, affected by non-specific mental retardation, and their mothers. We found a high proportion of carriers for phenylketonuria, defined as subjects having a percent probability of correct classification higher than 90. By this method, heterozygosity was detected in two child-mother couples, four individual children and five mothers.     

Chromosomal and biochemical screening on mentally retarded school children in Taiwan

Governmental officials as well as medical scientists in Taiwan have worked hard in recent years to develop and to implement various measures, such as prenatal diagnosis and neonatal screening, to lower the incidence of hereditary diseases and mental retardation in the population. An inquiry into the possibility of devising a chromosomal and biochemical screening program and to apply it routinely to all the mentally retarded school children island-wide was the major aim of the present study. A collection of 1,614 blood samples was screened for phenylketonuria (PKU), galactosemia, homocystinuria, biotinidase deficiency, and congenital hypothyroidism. The IQ of these children ranged from 50–75 (1,397 children, moderate group) to less than 50 (217 children, severe group). Six cases of PKU (one tetrahydrobiopterin deficient and five classical) and three cases of thyroid dysfunction were found. The overall incidence of these two diseases was 0.56%. Of the 1,614 blood samples, 1,323 were cultured and karyotyped successfully. One hundred and twenty-five of them had chromosome abnormalities. The majority (64 out of 125) were trisomy 21. A remarkable diffrence in the percentage of mentally retarded children with chromosome abnormalities was observed between the moderate (7.87%) and severe (17.51%) retardates.     

Ring chromosome 17 in a mentally retarded young man—clinical,cytogenetic, and biochemical investigations

A young, mentally retarded man with seizures was discovered to have a ring chromosome 17. He had no major anomalies. The phenotype associated with r(17) probably is variable. The patient's deletion and genotype allowed us to reduce further the chromosome location of the acid α-glucosidase gene.     

A genetic-diagnostic survey in an institutionalized population of 173 severely mentally retarded patients

In this report we summarize the findings in a genetic-diagnostic survey of an institutionalized population of 173 severely mentally retarded patients. The etiological study was based on a clinical genetic approach with special attention for dysmorphology and neurological findings. A constitutional disorder, as the direct cause of the severe mental handicap, was found in 75 patients (43.35%). A detailed survey of the different data and findings are given, and compared with the results of previous studies.     

A genetic diagnostic survey in a population of 202 mentally retarded institutionalized patients in the south of Brazil

Filix TM, Leite JCL, Maluf SW, Coelho JC. A genetic diagnostic survey in a population of 202 mentally retarded institutionalized patients in the south of Brazil. Clin Genet 1998: 54: 219–223. 0 Munksgaard, 1998
The Associaciio dos Pais e Amigos dos Excepciondis (APAE) is an institution for mentally retarded patients located at Caxias do Sul in the south of Brazil. A genetic diagnostic survey of 202 individuals from this institution is presented. The patients had a male:female ratio of 1.3:l and their ages vaned from 1 month to 47 years with a mean of 5.5 years. Using personal and family data, careful clinical examination and laboratory investigation, the authors established a definitive diagnosis in 132 patients (65.34%). A constitutional disorder was present in 111 patients (54.95%). Down's syndrome patients represented 32.15%, while I.98% had other chromosomal anomalies. In 15 patients (12.37%) a disorder of Mendelian inheritance was diagnosed. In 8 patients (3.96%) a multiple congenital anomalies/mental retardation (MCA/MR) syndrome was recorded. Eight patients (3.960/0) had a central nervous system (CNS) malformation. An acquired condition was observed in 21 patients (10.39%), including pre- or post-natal infections. In the remaining 70 patients (34.65%) a conclusive diagnosis was not possible.     

A clinical, cytogenetic and familial study of 307 mentally retarded, institutionalized, adult male patients with special interest for fra(X) negative X-linked mental retardation

In this study we report the results of a systematic etiological, clinical genetic study in 307 institutionalized mentally retarded adult males. Special attention is paid to the nosology of X-linked mental retardation. During the survey 63 males with one or more 'Martin Bell'-like features were identified in whom repetitive fragile Xq27-3 screenings were negative. In 13 of them, belonging to 9 different families, pedigree data were compatible with X-linked inheritance. This finding confirms the existence of one (or more) forms of fra(x) negative mental retardation with 'Martin Bell'-like features.     

A genetic-diagnostic survey in an institutionalized population of 158 mentally retarded patients. The Viaene experience

In this report we summarize the results of a genetic-diagnostic survey of an institutionalized population of 158 severely mentally retarded patients. The etiological study was based on a clinical genetic approach with special attention to dysmorphology and neurological findings. In 72 patients a constitutional cause of their mental impairment was found: a chromosomal abnormality in 21, a Mendelian disorder in 36 (autosomal recessive disorder: 23; autosomal dominant: 12; and X-linked recessive: 1), a MCA/MR syndrome in 9, and a CNS malformation in 6 patients. In 33 patients, a pre- or perinatal cause was found, and 20 patients presented a pre- or perinatal infection of the CNS. Finally, no etiological diagnosis was detected in 28 patients; 6 of them presented a hitherto unclassifiable type of familial mental retardation.     

An etiological survey of the severely retarded Hertfordshire children who were born between January 1, 1965 and December 31, 1967

An etiological survey is presented of all severely retarded children living in Hertfordshire, at home and in residential care, born between January 1, 1965, and December 31, 1967. One hundred and forty-six children (87 boys and 59 girls) were ascertained, out of a total population of 46,960, with a prevalence of 1 in 320 or 3.1 per 1,000. Approximately 1/3 (47) had the Down syndrome, 1 per 1,000 population. It was possible to establish a diagnosis in a further 45 cases, which included 1 additional case of autosomal chromosome abnormality and 7 each of autosomal dominant, recessive and X-linked conditions; 17 were associated with presumed multifactorial etiological factors; in 6 the condition was thought to have been caused by an environmental agent. It was not possible to establish a cause in the remaining 54 cases. Recurrence risks of severe mental retardation in cases where it is impossible to establish a definite diagnosis are discussed and the potential value, for genetic counseling purposes, of categorizing such patients into broad symptomatological groups, is suggested.     

Concurrence of ring 21 and trisomy 21 in children of normal parents

We present a case of two siblings with different chromosome 21 abnormalities that are both de novo [r(21)/i(21p13) mosaicism and rob(14;21)]. Molecular studies using polymorphic markers have shown that these two aberrations had a common maternal origin. However, the parents were cytogenetically and phenotypically normal. This unusual association has not been reported and is considered to be a unique case that should be addressed.     

Attachment, cognitive, and motor development in adopted children: short-term outcomes after international adoption

OBJECTIVE: To examine infant attachment and developmental functioning shortly after international adoption. METHODS: At 14 months, infant-mother attachment and mental (MDI) and psychomotor (PDI) development were assessed in 70 internationally adopted children. Mean age at arrival was 5.5 months, mean stay in the adoptive family 8.7 months. RESULTS: Adopted children's MDI and PDI did not deviate from normative scores. Also, their secure-insecure attachment distribution was comparable with that of normative groups. However, more adoptees were disorganized attached (36 vs. 15% in normative groups). Temporary residence in a foster home in the country of origin before adoption was related to higher MDI and PDI, whereas disorganized attachment in the adoptive family was related to lower MDI and PDI scores. CONCLUSIONS: The majority of internationally adopted children form secure attachment relationships and function at normative developmental levels shortly after adoption. Residence in a foster family before adoption may partly prevent developmental delays.     

Down syndrome in a population of elderly mentally retarded patients: Genetic-diagnostic survey and implications for medical care

Ninety-six adults with Down syndrome (DS) from an institutional setting of 591 mentally retarded were investigated systematically with respect to cytogenetic diagnosis, mental functioning and dementia, ophthalmological and audiological abnormalities, and thyroid function. Seventy of the 96 DS patients (73%) were older than 40 years. Only 4.2% were females. Trisomy 21 was found in 86% and mosaic trisomy 21 in 13%. Eighty-two percent of the patients were moderately or severely mentally retarded, 15% were profoundly retarded, and only 3% mildly retarded. Nineteen percent of the patients had dementia. This number increased to 42% of the patients above the age of 50 years. Epileptic seizures were present in 16.7% of all patients, and in 50% of the patients with dementia. Only 17% of the patients in the present study had normal visual acuity, one-third had at least moderately reduced vision. This number increased significantly with age: in the age group 50–59 years almost half of the patients had moderate to severe vision loss. Seventy percent of the patients had moderate, severe, or very severe hearing loss, which was undiagnosed before systematic hearing testing was performed. Increased (48%) or decreased (1%) TSH level was found in 49% of the patients examined for thyroid functions. We suggest a regular screening of all adults with DS to diagnose early dementia, epilepsy, hypothyroidism, and early loss of visual acuity and hearing, with special attention to the group of patients who are severely to profoundly mentally retarded and those with advanced age. Cytogenetic studies are necessary to confirm the clinical diagnosis and are essential for genetic counseling purposes. Am. J. Med. Genet. 85:376–384, 1999. © 1999 Wiley-Liss, Inc.     

Recurrent de novo interstitial deletion of 16q in two mentally retarded sisters

Two sisters with similar clinical features are described. Their clinical manifestations include mental retardation, delayed speech development, low percentiles for height, weight and head circumference, dysmorphic ears, cubitus valgus, pseudoclubbing of fingers, flexion deformity of toes, small kidneys, elevated serum creatinine and blood urea nitrogen (BUN). High resolution chromosome analysis revealed a complete deletion of 16qh with a concurrent small deletion of the adjacent euchromatic segment 16q12.1 in one of the no. 16 chromosomes of both sisters, whereas the parents had normal no. 16 chromosomes. Length polymorphism of the 16qh regions appeared to indicate a maternal origin of the deleted no. 16 chromosome in both sisters. The clinical features of both sisters were attributed to the 16q12.1 deletion. Since both parents were cytogenetically normal, the two sisters were considered as a recurrence of a similar de novo interstitial deletion. Possible mechanisms which could lead to recurrence of a seemingly de novo event are discussed.