X-linked mental retardation with Marfanoid habitus: a changing phenotype with age?

In this report, we present two further examples of X-linked mental retardation with Marfanoid habitus. Follow-up data on these two patients reveal that the clinical diagnosis of this syndrome is extremely difficult, if not impossible before puberty, as the Marfanoid habitus only becomes strikingly evident during adolescence.     

Small metacentric nonsatellited extra chromosome

Summary Five mentally retarded male patients with a supernumerary small metacentric nonsatellited chromosome were found to have many clinical features in common. The face showed characteristic small crowded features, the bodily habitus was asthenic, and the hands and feet had minor abnormalities. Renal anomalies were present in two patients. One patient had a myelomeningocele.Cytogenetic studies employing Q, R, and C banding in four patients showed the small extra chromosome to have staining properties compatible with an isochromosome of the short arm of chromosome 18.A comparison with previous case reports suggests a new syndrome. However, the identity of the extra chromosome has not yet been determined.     

On the occurrence of macroorchidism and mental handicap in the Aarskog syndrome

In this report we present follow-up on two moderately mentally retarded boys with Aarskog syndrome. As 22 other mentally normal Aarskog patients these two boys presented a catch-up after a delayed puberty with a final adult height of 160 cm. A remarkable finding was the development of macroorchidism in two mentally retarded Aarskog patients. The pathogenesis of macroorchidism in the fragile X syndrome and in other X-linked mental retardation syndromes is discussed.     

On the nosology of moderate mental retardation with special attention to X-linked mental retardation. A diagnostic genetic survey of 274 institutionalized moderately mentally retarded men

In this paper we report the results of a genetic-diagnostic survey of 274 institutionalized moderately mentally retarded adult males and compare these data with those from our previous studies in the severely mentally retarded and from a comparable population of 262 institutionalized moderately mentally retarded males and females (The Borgenstein experience). Special attention is paid to the nosology of X-linked mental retardation and familial mental retardation in general.     

Martin-Bell phenotype in males with acquired central nervous system lesions. 15 males diagnosed during a systematic etiological study of 274 mentally retarded males

Martin-Bell phenotype in males with acquired central nervous system lesions. 15 males diagnosed during a systematic etiological study of 274 mentally retarded males: After a brief survey of the etiological findings in 274 moderately mentally retarded adult males, we present data on the phenotypic features in the group of 65 patients with a acquired (pre-, peri- or postnatal) cause of their handicap. In 15 of them "Martin-Bell stigmata" were observed i.e. they had 3 or more symptoms as found in fra(X) positive "Martin-Bell" males. These data are a further indication for a disregulation of the cortico-hypothalamico-hypophyseal axis in the fra(X) syndrome.     

Screening for fragile X syndrome among Brazilian mentally retarded male patients using PCR from buccal cell DNA

Fragile X syndrome is one of the most frequent causes of mental retardation. Since the phenotype in this syndrome is quite variable, clinical diagnosis is not easy and molecular laboratory diagnosis is necessary. Usually DNA from blood cells is used in molecular tests to detect the fragile X mutation which is characterized by an unstable expansion of a CGG repeat in the fragile X mental retardation gene (FMR1). In the present study, blood and buccal cells of 53 mentally retarded patients were molecularly analyzed for FMR1 mutation by PCR. Our data revealed that DNA extraction from buccal cells is a useful noninvasive alternative in the screening of the FMR1 mutation among mentally retarded males.     

Cytogenetic investigations in mentally retarded and normal males from 14 families with the fragile site at Xq28

Summary Lymphocyte cultures from 27 mentally retarded males aged 1 year to 77 years, and from 11 normal brothers from a total of 14 families with the fragile X segregating have been examined cytogenetically employing three different culture methods including methods for induction of fra(X) by FUdR (fluorodeoxyuridine) or MTX (methotrexate). All mentally retarded males showed unequivocal fra(X) expression. No statistically significant correlation between fra(X) expression and age could be demonstrated. No enhancement with FUdR was observed. Fibroblast cultures from 10 retarded males expressed fra(X) in a dose-response relationship to increasing concentrations of FUdR. None of the normal males showed fra(X). In vivo folic acid treatment of seven mentally retarded males resulted in marked reduction in fra(X) expression in lymphocyte cultures grown in medium 199. However, reinduction was achieved by FUdR or MTX, except in one case who temporarily received very high doses of folic acid.     

Variational chronoreflexometric evaluation of the central nervous system functions in elementary school children with mental retardation

Parameters of variational chronoreflexometry variation curve of distribution were shown to correlate with the level of mental development in mentally retarded children. The borderline values of the CNS function condition's criteria were determined for both normal children and those mentally retarded. A feasibility of assessing the interhemisphere functional asymmetry by means o this particular method, was shown.     

Prevalence of the fragile X syndrome in four birth cohorts of children of school age

Summary The prevalence of the fragile X syndrome among 12,882 children (6594 boys and 6288 girls) born during the years 1969–1972 in Kuopio province in eastern central Finland has been studied retrospectively. Mentally retarded children were selected from normal schools by using school achievement tests and from registers of mentally retarded individuals. In the present study fragile X syndrome was found in 6/111 mentally retarded children (5.4%), in 4/61 boys and in 2/50 girls, respectively. It was not detected in the control group of 85 healthy children. The corrected prevalence of fragile X syndrome among boys in four successive birth cohorts was estimated to the 1 in 1210 or 0.8/1000, and that among girls, 1 in 2418 or 0.4/1000. The overall prevalence was calculated to be 1 in 1612 or 0.6/1000 children.     

Observations on Community School Facilities for the Mentally Retarded and Admissions to Institutions in Ontario, 1954-63

The relationship between community school facilities and first admissions of mentally retarded children to Ontario Institutions was investigated for the period 1954-1963. The number of educable (I.Q. 50-75) mentally retarded children aged 6-16 years in community schools rose consistently (92.1/100,000 population in 1954 to 190.1 in 1963), while first admissions of educable mentally retarded persons aged 5-19 years to Ontario Hospital Schools showed no consistent trend (2.0/100,000 in 1954 and 2.0 in 1963). The number of trainable (I.Q. 20-50) mentally retarded children aged 5-18 years in community retarded children''s schools rose steadily (10.9/100,000 population in 1954 to 42.8 in 1963), while first admissions in this category aged 5-19 years demonstrated no consistent trend (2.6/100,000 in 1954 and 2.2 in 1963).No indication was found that the age distribution of these first admissions had changed from 1954 to 1963. Any effect that increased school facilities might have had in reducing first admissions may have been nullified by the very large demand for a limited number of beds.     

Partial trisomy 22q with elevated arylsulfatase-A activity.

A two years-old, severely mentally retarded male is reported with 22q trisomy. After the recent confirmation of the localisation of arylsulfatase-A (ARSA) on chromosome 22, the elevated activity of this enzyme (about 1,5 times the normal values) in the present patient may be another example of a gene dosage effect in autosomal imbalance.     

A Survey of Toxoplasmosis Among Mentally Retarded Children

To determine what role, if any, toxoplasmosis plays in the mental retardation of children, sera from 345 mentally retarded children were tested for the presence of antibodies to Toxoplasma gondii. The serological tests employed were the complement-fixation, the Sabin-Feldman dye test and the immunofluorescence test. The donors were also skin-tested with toxoplasmin.Of 345 mentally retarded donors nine gave a positive skin reaction, 15 possessed complement-fixing antibodies, 21 had immunofluorescent antibodies and 45 had dye test antibodies to T. gondii.The incidence of antibodies to T. gondii in the mentally retarded group was approximately the same as in the normal control group of the same age, and less than in the group suspected of having toxoplasmosis. It is concluded that in the children in this study toxoplasmosis played little or no role as a predisposing factor in the occurrence of congenital mental deficiency.     

Distinct dysmorphic syndrome in a child with inverted distal 5q duplication

In the present paper we report a moderately mentally retarded 3 1/2-year-old girl with distal inverted 5q duplication (karyotype 46,XX,inv dup(5)(pter----q35.3::q35.3----q32::q35.3----qter). A distinct dysmorphic syndrome was present corresponding to the socalled "B-type" phenotype in 5q duplications, due to a duplication of band 5q33.     

Amebiasis in institutions for the mentally retarded in Kanagawa Prefecture, Japan

A parasitologic survey of 620 mentally retarded patients, institutionalized in five different facilities in Kanagawa Prefecture, revealed a high incidence (12.6%) of infection with Entamoeba histolytica. A concomitant serologic survey, by the indirect fluorescent antibody test, gave a much higher incidence (26.5%). Moreover, most zymodeme patterns of the amebae isolated from infected individuals were of a pathogenic type (Zymodeme II). Our findings demonstrate that the mentally retarded in Japan, as in the United States, still are plagued by a high rate of amebic infection.     

应用多聚酶链式反应快速分析FMR-1基因突变

为了建立一种在先天性智力低下患儿中快速分析脆性X综合征智力低下基因1(Fragile X mental retardation gene 1.FMR-1)突变的方法,对先天性智力低下儿童进行脆性X综合征的大面积筛查和诊断,应用复式多聚酶链式反应一次性扩增FMR-1基因的(CGG)n的重复区,分析CGG重复序列的大小,判断FMR-1基因状态(正常、突变前、突变后),对脆性X综合征可疑患儿快速筛查,在113倒不明原因的先天性智力低下患儿中,分析有脆性X综合征携带者(FMR-1基因前突变者)7例(2男5女),脆性X综合征患者(FMR-1基因突变者)5例,应用多聚酶链式反应可以对脆性X综合征可疑患儿进行大面积初筛,确定携带者和患者。     

A new case of a syndrome including marfanoid phenotype and craniostenosis]

A new case of the syndrome with craniosynostosis and Marfanoid features is reported. The data presented and the analysis of relevant literature are suggestive of a community of the Marfanoid features with clinical and genetic heterogeneity. The possibility to delineate the Marfanoid syndrome with craniosynostosis as a nosologic unit and its etiology are discussed.     

A cytogenetic study of mentally retarded school children in taiwan with special reference to the fragile X chromosome

Summary A cytogenetic study was made on 341 mentally retarded children in the Provincial Nantou Rehabilitation Center for the Mentally Retarded and the St. Raphael Opportunity Center in Tainan. Of the 89 mentally retarded children with chromosomal abnormalities, 63 had Down syndrome, 13 had the fragile X [fra(X)] syndrome, and the remaining had other aneuploid constitutions. Family studies were possible for 2 of the 13 fra(X) probands. The results of this study illustrate the contribution of chromosomal abnormalities to the pathogenesis of mental retardation in children.     

Partial trisomy of the short arm of chromosome 3 (3p25→3pter)

Summary Two profoundly mentally mentally retarded brothers with partial trisomy for the distal part of the short arm of chromosome 3 (3p253pter) are described. Their anomaly arose as a segregation product of a balanced t(3p-;18q+) translocation in the mother. Compared with the other cases of partial 3p trisomy reported up to now, the present patients display a similar craniofacial dysmorphism with hypertelorism, broad nasal tip, short upper lip with prominent philtrum, and a large mouth with down-turned corners. Other stigmata, such as a prominent, high forehead with frontal bossing and full cheeks, were present during childhood but progressively disappeared.     

Population cytogenetics of folate-sensitive fragile sites

Summary The frequencies of folate-sensitive autosomal rare fragile sites (ARFS) were compared in populations of mentally retarded, mentally subnormal, and mentally normal children and of patients referred for diagnostic chromosome study. The frequencies did not differ significantly. Altogether, an autosomal rare fragile site was found in 16 of 1445 individuals (1 in 90). Of six different folate-sensitive ARFS detected, the most common one was FRA9A, with a frequency of 1 in 241 individuals. In addition, FRA17A, classified as a distamycin A-inducible fragile site, was found with a frequency of 1 in 206. It was regarded as a spontaneously expressive fragile site. In 19 families in which transmission of an autosomal rare fragile site was studied, the mother was the carrier in 16 families and the father, in one family. The mean percentage (±SD) of cells expressing ARFS in 55 individuals was 19% (±11.4). The age did not affect the rate of expression. When the rate of expression was calculated separately in a group of mentally retarded (mean=23.4%) and in a group of mentally normal individuals (mean=16.0%), the difference was statistically significant.     

Mutations in ZDHHC9, which encodes a palmitoyltransferase of NRAS and HRAS, cause X-linked mental retardation associated with a Marfanoid habitus

We have identified one frameshift mutation, one splice-site mutation, and two missense mutations in highly conserved residues in ZDHHC9 at Xq26.1 in 4 of 250 families with X-linked mental retardation (XLMR). In three of the families, the mental retardation phenotype is associated with a Marfanoid habitus, although none of the affected individuals meets the Ghent criteria for Marfan syndrome. ZDHHC9 is a palmitoyltransferase that catalyzes the posttranslational modification of NRAS and HRAS. The degree of palmitoylation determines the temporal and spatial location of these proteins in the plasma membrane and Golgi complex. The finding of mutations in ZDHHC9 suggests that alterations in the concentrations and cellular distribution of target proteins are sufficient to cause disease. This is the first XLMR gene to be reported that encodes a posttranslational modification enzyme, palmitoyltransferase. Furthermore, now that the first palmitoyltransferase that causes mental retardation has been identified, defects in other palmitoylation transferases become good candidates for causing other mental retardation syndromes.