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.     

Index to Soviet Psychology,Volume XV (Fall 1976-Summer 1977)

It is a well-known fact that males predominate among the mentally retarded. Various explanations for this have been offered—among others, more exposure of the male fetus to external pathogenic influences in the antenatal period, a lower threshold of appearance of mutant polygenes responsible for mental retardation in males, or a high frequency of X-linked mental retardation [1]. The first two hypotheses have not been confirmed. Although a lower threshold of appearance of mental retardation in males has been demonstrated [2], this cannot explain such a major quantitative divergence between males and females as exists in mental retardation. It has not been easy to confirm the third hypothesis since the forms of X-linked hereditary pathology frequently appear sporadically, i.e., in only one boy in a family.     

Aerobic work capacity of mentally retarded boys and girls in junior high schools.

The maximal oxygen uptake (Vo2 max) and ergometer load at a heart rate of 170 beats/min (PWC170) were determined in mentally retarded children (74 boys and 53 girls) of ages 12-15, whose IQ ranged from 36 to 91, and the results were compared with those for normal children. Mentally retarded boys and girls showed significantly inferior body height and weight, but no significant difference was found in skinfold thickness. The mean value of PWC170 for boys and girls was 14.34 kpm/kg/min and 11.31 kpm/kg/min, respectively, significantly less than that of the normal group. The mentally retarded boys had mean VO2 max per unit body weight of 42.4 ml/kg/min, which was significantly less than the 51.2 ml/kg/min of normal boys. The mentally retarded girls had a mean of 33.1 ml/kg/min which was also less than the 41.3 ml/kg/min of normal girls. The correlation coefficient between body weight and PWC170 (kpm/min) was 0.711 and 0.720 for boys and girls, respectively, while that between body weight and VO2 max (liter/min) was 0.641 for boys and 0.656 for girls. No significant correlation was found between IQ and PWC170 (kpm/kg/min) nor between IQ and VO2 max (ml/kg/min) both for boys and for girls. Similarly, no significant correlation was found between mental age and the VO2 max value (ml/kg/min).     

Mentally retarded children of eastern India: A biosocial study

Abstract

Biosocial characteristics of 265 mentally retarded and 253 nonretarded children comprising 518 handicapped children from eastern India were studied to discern characteristics significantly associated with the retardates. The children studied were consecutive referrals between January 1977 and April 1981 to the Centre for Handicapped Children, Institute of Child Health, Calcutta. Comparison of retarded and nonretarded children showed the incidence of mental retardation to be significantly associated with age of children, age of mothers, parents’ socioeconomic class, family size, birth order, tempo of motor development, and family history of psychiatric illness. The proportion of retardates was higher among the handicapped girls than among boys, and the level of retardation was significantly associated with sex. Implications of findings are 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.     

High prevalence of aspartylglycosaminuria among school-age children in eastern Finland

Summary A high prevalence of the lysosomal storage disease aspartylglycosaminuria was found in a study of four birth cohorts of 12882 children in eastern Finland. Using school achievement tests and registers of mentally retarded individuals, 178 mentally retarded children were identified. Randomized urine samples from 151 of the 178 retarded children and from 101 healthy children were analyzed quantitatively for aspartylglucosamine by high-performance liquid chromatography. The results identified three affected individuals in the retarded group indicating an exceptionally high prevalence of aspartylglycosaminuria (1:3643) in the study population, consistent with a carrier frequency of 1:30. The 95% confidence limits for the prevalence are 1:4 352-1:16389. This is the highest prevalence described for any glycoproteinosis in any population and comparable to the incidence figures of the most common lysosomal storage diseases, Gaucher disease type I and Tay-Sachs disease among Ashkenazi Jews. In the study group, aspartylglycosaminuria was, after trisomy 21 (n = 19) and the fragile X syndrome (n = 6), the most common genetic cause for mental retardation.     

The prevalence of minor physical anomalies in mentally retarded children

The prevalence of minor physical anomalies was examined in a sample of 109 children with idiopathic mental retardation (65 boys and 44 girls). Control group consisted of 246 healthy schoolchildren (123 boys and 123 girls) aged 8 to 12 years. A comparison was made between number of found minor anomalies per child (W1) and their Waldrop weight scores (W2) in healthy and mentally retarded (MR) children. The MR children were found to have a higher number of minor anomalies per child. In their group predominated those with four or more anomalies (56.9%), whereas among healthy children only 7.7% had four anomalies or more. In contrast to the high weighted score value (W2) of five or greater in 36.7% of MR children, it was absent in all control group subjects. There were highly significant differences between the MR and healthy children in the average value of the number of minor anomalies per child (W1) and in the average weighted score (W2). The average number of minor anomalies per child (W1) in MR and well children was 3.65 and 1.7, respectively. In MR children the average weighted score (W2) was 3.82, being 1.46 in healthy children. Our results suggest that common etiological factors, which had led to a physical and mental disorder, were active early in the development of MR children. The finding of high incidence of multiple minor anomalies in MR children indicates that genetic factors may play an important role in the etiology of the underlying disorder in the child group studied.     

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.     

Causes of precocious puberty in children referred for evaluation in hospital conditions

INTRODUCTION: Symptoms of precocious puberty (PP) in children always arouse anxiety in their parents. Many children with PP are being hospitalized for the detailed diagnostic work-up. The aim of our study was to analyze the frequency of the variants of PP in children referred to our department. MATERIAL: Retrospective analysis of 119 children (103 girls and 16 boys) referred for hospitalization in the years 2003-2005 due to signs of precocious puberty was performed. RESULTS: Premature thelarche, benign variant of puberty, was diagnosed in 62 (53%) girls, in the mean age of 3.39 (+/- 2.33) years. Their mean height was within 0.7 +/- 1.1 SD. Premature pubarche was diagnosed 30 (25%) children--22 girls and 8 boys in the mean age was 7.24 (+/- 0.81) years. Their mean height was 1.3 +/- 1.0 SD and was significantly higher than normal (p < 0.0001). Premature menarche was diagnosed in 8 (7%) girls in the mean age 4.81 +/-2.26 years. Mean height in this group was normal for age (0.9+/-0.8 SD). PP was diagnosed in 19 (16%) children (11 girls and 8 boys) in the mean age 5.91 +/- 1.63 years. Mean height in this group was 1.6 +/- 0.7 SD, and was significantly higher than the mean for age (p<0.0005). GnRH-dependent type was present in 15 children, diagnosed as idiopathic in 9 girls and 1 boy. In 5 children (4 boys and 1 girl) pathology of central nervous system was found. In 4 children GnRH-independent precocious puberty was diagnosed--in 3 caused by congenital adrenal hyperplasia and in 1 boy by tumour of testis (leydigioma). CONCLUSIONS: Girls with precocious thelarche without growth acceleration present the benign variant of puberty and need clinical follow up only. Boys with clinical signs of precocious puberty should be carefully evaluated to rule out the organic cause.     

Chromosome X-linked mental retardation and marfanoid syndrome

In the present paper we report two pairs of slightly to moderately mentally retarded brothers with Marfanoid habitus and similar craniofacial changes. They had a long and narrow face, small mandible, high-arched palate and hypernasal voice, as previously reported by Lujan et al. (1984) in 4 mentally retarded males of a large kindred. The present data suggest the existence of a specific type of X-linked mental retardation with Marfanoid habitus.     

Frequency of the fragile X syndrome in institutionalized mentally retarded females in Japan

Summary The fragile X [fra(X)] syndrome was screened on 190 Japanese institutionalized females with moderate to severe mental retardation. Two inmates with severe mental retardation (IQ 20) had the fra(X) chromosome in 26% and 15% of the cells examined, indicating that the prevalence of the fra(X) syndrome was about 1% in all female inmates and was about 3.27% in severely mentally retarded females with known causes. However, no female with fra(X) syndrome was found in 35 moderately retarded females. Both had brothers with the fra(X) syndrome and the prevalence was 10% in females with a family history of mental retardation. In addition, the replication study of the fra(X) chromosome in the patients supported the proposal that an excess of the early replicated fra(X) chromosome is related to the mental capacity in heterozygous females. Therefore, the fra(X) syndrome should not be ignored even in severely mentally retarded females with a family history, though the heterozygotes are commonly normal to subnormal in their mental development. in addition, the replication study of the fra(X) chromosome may help to estimate mental development in the carrier children.     

Patterns of urinary aminoacid excretion in exceptional children and patients with mental disorders in Costa Rica

The amino acid profile was studied in individual random samples of urine from 1147 normal schoolchildren and 1074 exceptional children: 628 with mental retardation, 332 with hearing and speech defects and 114 with visual defects as well as in 673 patients with mental disorders. Laboratory procedures included chemical tests and one-dimension paper- electro- and column-chromatography. Phenylketonuria was found in a mentally retarded girl and in one of her brothers; iminoglycinuria in a mentally retarded boy and heterozygote cystinuria in a man with manic-depressive psychosis. The percentage of high excretors of beta-aminoisobutyric acid (B-AIB) in the controls (4.88%) was similar to previous findings in the Caucasian race. The children with hearing and speech defects showed a number of high excretors of B-AIB significantly lower (X2 = 5.32; p less than 0.025) and the children with visual defects a number of hyperglycinurias significantly higher (X2 = 9.19; p less than 0.05). Previous non-consistent findings on the excess of high excretors of B-AIB in Down's syndrome were not confirmed in this study. These results suggest a relationship between transport defects in the plasma membrane and pathological disorders in some of the cases screened.     

Association of pharmacological tests and study of 24-hour growth hormone secretion in the investigation of growth retardation in children: analysis of 257 cases

Growth hormone (GH) secretion can presently be investigated by several methods: pharmacological provocative tests, study of 24-h GH secretion, measurement of somatomedin-C (Sm-C)/insulin-like growth factor (IGF) I, and the growth hormone-releasing hormone (GHRH) test. In order to compare the results obtained, these methods were used in 257 children with growth retardation (169 boys, 88 girls). Their height SD was -2.7 +/- 0.2, chronological age 11 3/12 +/- 1 6/12 years, and bone age 8 4/12 +/- 1 4/12 years. Mean growth velocity was 4.5 +/- 1.5 cm/year. One hundred and thirty-eight boys and 80 girls were prepubertal, and 31 boys and 8 girls were pubertal (B2 G2). All children underwent the study of 24-h GH secretion (n = 257) and pharmacological provocative tests (two tests, n = 213; one test n = 44). Sm-C/IGF I was measured in prepubertal children (n = 131), and a GHRH test was carried out (n = 153). In addition, the mean integrated concentration of growth hormone secretion (IC-GH) was assessed in a control group of 23 children and was found to be 5.4 +/- 1.2 ng/ml/min. The IC-GH in the group as a whole was 2.6 ng/ml/min. The mean maximum peak during pharmacological tests varied considerably according to the test used, ranging from 7.8 ng/ml for the arginine test to 17.1 ng/ml for the glucagon and betaxolol test. The maximum peak and the 24-h IC-GH were not significantly correlated.(ABSTRACT TRUNCATED AT 250 WORDS)     

X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family

A large French family including members affected by nonspecific X-linked mental retardation, with or without autism or pervasive developmental disorder in affected male patients, has been found to have a 2-base-pair deletion in the Neuroligin 4 gene (NLGN4) located at Xp22.33. This mutation leads to a premature stop codon in the middle of the sequence of the normal protein and is thought to suppress the transmembrane domain and sequences important for the dimerization of neuroligins that are required for proper cell-cell interaction through binding to beta-neurexins. As the neuroligins are mostly enriched at excitatory synapses, these results suggest that a defect in synaptogenesis may lead to deficits in cognitive development and communication processes. The fact that the deletion was present in both autistic and nonautistic mentally retarded males suggests that the NLGN4 gene is not only involved in autism, as previously described, but also in mental retardation, indicating that some types of autistic disorder and mental retardation may have common genetic origins.     

Effect of growth hormone therapy on IGF-I, bone GLA-protein and bone mineral content in short children with and without chronic renal failure.

Chronic renal failure (CRF) in the young is complicated by, among other conditions, growth retardation, hyperparathyroidism and uremic osteodystrophy. Many children with CRF are now being treated with growth hormone (GH). Since GH has a direct mitogenic effect on osteoblasts in culture, we studied the effects of GH therapy on osteoblastic activity, such as serum alkaline phosphatase (AP), bone GLA-protein (BGP) and bone mass density (BMD) in poorly growing children with and without CRF. Fifteen (4 girls, 11 boys) healthy children with short stature (SS) and 10 (3 girls, 7 boys) children with end-stage renal failure (CRF) 4.5-12.4 years of age were treated with daily subcutaneous injections of GH in a dose of 0.1-0.125 IU/kg/day for 1 year. IGF-I, BGP and BMD of the spine were determined before and after the year of treatment. During GH therapy, a similar increase in height velocity and IGF-I were noted in SS and CRF groups: 3.8 +/- 0.77 to 8.38 +/- 1.25 (p < 0.001) vs. 4.0 +/- 0.6 to 7.14 +/- 1.3 cm/year (p < 0.001) and 7.8 +/- 2.6 to 21.8 +/- 7.5 (p < 0.01) vs. 7.9 +/- 1.3 to 21.5 +/- 5.6 nmol/l (p < 0.01), respectively. AP increased from 205 +/- 27 to 274 +/- 50 IU/l (p < 0.01) in the SS group but not in CRF patients (223 +/- 58 pre- 218 +/- 51 IU/l post-GH therapy).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Growth response to growth-hormone administration during the decelerating phase of the pubertal growth spurt in short normal children

In order to investigate the value of growth hormone (GH) treatment during late puberty, we studied the effect of human GH (hGH) administration (0.85 +/- 0.30 IU/kg/week; range: 0.44-1.28) on height velocity (HV) after the peak of the pubertal growth spurt in a group of 10 (4 girls and 6 boys) short normal children (GH peak after pharmacological stimulation: 15.5 +/- 2.3 ng/ml) with growth retardation (height: 2.6 +/- 0.3 SD) and puberty Tanner stage 4. A group of 10 untreated children, observed prior to the study, served as controls. The children were regularly measured during their pubertal growth spurt, and HV (cm/year) was calculated every 6 months. The pretreatment evaluation consisted of 2 consecutive 6-month periods characterized by a decrease in HV of at least 25%. In the group of selected children, hGH administration was then initiated and growth variables were evaluated after 6 and 12 months of therapy. Skeletal maturation was evaluated at the beginning as well as after 6 months and 12 months of hGH therapy. In the controls, HV (mean +/- SD) had decreased from 8.8 +/- 1.8 to 4.9 +/- 1.4 cm/year during the pretreatment period (in girls from 7.9 +/- 1.4 to 4.1 +/- 0.6 cm/year and in boys from 9.6 +/- 1.6 to 5.8 +/- 1.2 cm/year). During the following semester, HV was 3.3 +/- 0.8 cm/year (girls: 3.4 +/- 1.0 and boys: 3.2 +/- 0.2 cm/year).(ABSTRACT TRUNCATED AT 250 WORDS)     

Mental retardation linked to fragility of chromosome X: current knowledge

The association of the fragile X chromosome with X-linked mental retardation is now well established. The main clinical features are mental retardation, typical facial dysmorphism and macroorchidism. Cytogenetically there is a fragile site in band Xq27-28 which can be demonstrated using specific techniques. The genetic studies are compatible with a X-linked dominant inheritance with an incomplete penetrance. A preliminary estimation of an overall frequency of 1: 2000 males for the fra(X)(q) condition is suggested.     

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.