Autism spectrum disorder profile in neurofibromatosis type I.

Neurofibromatosis Type 1 (NF1) is a common autosomal dominant single-gene disorder, in which the co-occurrence of autism spectrum disorder (ASD) has attracted considerable research interest recently with prevalence estimates of 21-40%. However, detailed characterization of the ASD behavioral phenotype in NF1 is still lacking. This study characterized the phenotypic profile of ASD symptomatology presenting in 4-16 year old children with NF1 (n = 36) using evidence from parent-rated Social Responsiveness Scale and researcher autism diagnostic observation Scale-2.

The social behavioral phenotype in boys and girls with an extra X chromosome (Klinefelter syndrome and Trisomy X): a comparison with autism spectrum disorder.

The present study aimed to gain more insight in the social behavioral phenotype, and related autistic symptomatology, of children with an extra X chromosome in comparison to children with ASD. Participants included 60 children with an extra X chromosome (34 boys with Klinefelter syndrome and 26 girls with Trisomy X), 58 children with ASD and 106 controls, aged 9 to 18 years. We used the Autism Diagnostic Interview, Social Responsiveness Scale, Social Anxiety Scale and Social Skills Rating System.

Early detection of chromosome 9q22.32q31.1 microdeletion and the nevoid basal cell carcinoma syndrome.

We report on a patient with a microdeletion of chromosome region 9q22.32q31.1 including the PTCH1 gene (human homologue of the Drosophila patched 1 gene), review the findings in the reported patients with similar array CGH findings, and highlight the non nevoid basal cell carcinoma/non-Gorlin syndrome findings at an earlier age.

X-linked mental retardation, short stature, microcephaly and hypogonadism maps to Xp22.1-p21.3 in a Belgian family.

X-linked mental retardation (XLMR) is a heterogeneous disorder that can be classified as either non-specific (MRX), when mental retardation is the only feature, or as syndromic mental retardation (MRXS). Genetic defects underlying XLMR are being identified at a rapid pace, often starting from X-chromosomal aberrations and XLMR families with a well-defined linkage interval. Here, we present a new family with a syndromic form of XLMR, including mild mental retardation, short stature, microcephaly and hypogonadism.

Screening for FMR-1 premutations in 122 older Flemish males presenting with ataxia.

Recently, Hagerman et al described the occurrence of a late-onset neurological disorder in five male carriers of the fragile-X (FMR-1) premutation. The major characteristics of this disorder, designated the Fragile-X Tremor Ataxia Syndrome (FXTAS), are progressive intention tremor, cerebellar ataxia and cognitive decline. Most cases of FXTAS published thus far were ascertained through families with a known fragile-X proband.

Inv(X)(p21.1;q22.1) in a man with mental retardation, short stature, general muscle wasting, and facial dysmorphism: clinical study and mutation analysis of the NXF5 gene.

We describe a 59-year-old male (patient A059) with moderate to severe mental retardation (MR) and a pericentric inversion of the X-chromosome: inv(X)(p21.1;q22.1).

A third MRX family (MRX68) is the result of mutation in the long chain fatty acid-CoA ligase 4 (FACL4) gene: proposal of a rapid enzymatic assay for screening mentally retarded patients.

Background: The gene encoding fatty acid CoA ligase 4 (FACL4) is mutated in families with non-specific X linked mental retardation (MRX) and is responsible for cognitive impairment in the contiguous gene syndrome ATS-MR (Alport syndrome and mental retardation), mapped to Xq22.3. This finding makes this gene a good candidate for other mental retardation disorders mapping in this region.

A distinct neurocognitive phenotype in female fragile-X premutation carriers assessed with visual attention tasks.

Premature ovarian failure (POF) and underlying hormonal changes are recognized as a distinct phenotype in female fragile-X premutation carriers. Neurocognitive deficits, in particular mental retardation, are associated with the full mutation in males and females. In female full mutation carriers this neurocognitive phenotype is expressed more mildly than in males.

Clinical study and haplotype analysis in two brothers with Partington syndrome.

Partington et al. [1988] described a three-generation family (MRXS1, MIM *309510, PRTS) with a syndromic form of X-linked mental retardation (XLMR). The clinical features in 10 affected males included mild to moderate MR, dystonic movements of the hands, and dysarthria.

Prader-Willi syndrome: new insights in the behavioural and psychiatric spectrum.

Prader-Willi syndrome (PWS) is a genetic disorder caused by the loss of the paternal contribution of the proximal part (15q11-q13) of the long arm of chromosome 15 (i.e. deletion, disomy and imprinting mutation).

Unusual chromosomal mosaicism in Wolf-Hirschhorn syndrome: del(4)(p16)/der(4)(qter-q31.3::pter-qter).

We report on the unusual cytogenetic findings in a girl with moderate mental retardation and a mosaic karyotype 46,XX,del(4)(p16)/46,XX,der(4)(qter-q31.3::pter-qter). The facial features observed in the child initially did not suggest the diagnosis of Wolf-Hirschhorn syndrome (WHS), but the distinct facial gestalt became obvious at prepubertal age.

Phenotypic checklist to screen for fragile X syndrome in people with mental retardation.

The development of a phenotypic checklist for identifying people with fragile X syndrome is described. The checklist was designed to identify people with developmental disabilities of unknown causes for molecular genetic testing for fragile X syndrome. The list consists of 28 items (7 on physical characteristics and 21 on behavioral features).

Longitudinal changes in cognitive and adaptive behavior in fragile X females: a prospective multicenter analysis.

In prospective studies of young, fragile X [fra(X)] males with the full mutation, cognitive abilities (IQ scores) and adaptive behavior levels (DQ scores) declined in most subjects tested. Little is known about longitudinal changes in IQ and DQ scores in young fra(X) females, although one earlier retrospective study showed declines in IQ scores in 8 of 11 subjects. To examine fra(X) females prospectively, we tested and retested 13 females with the full mutation, age 4 to 15 years.

Prader-Willi syndrome and psychotic symptoms: 1. Case descriptions and genetic studies.

Six people with Prader-Willi syndrome (PWS) who developed psychoses are described. Along with other literature reviewed in the present paper, the results imply an association between PWS and psychotic symptoms. Genetic studies were possible in five cases and SNRPN expression was examined in three cases.

New findings in the behavioral profile of young FraX females.

Nine girls, with a 50% risk to be carrier of the FMR-1 gene and who attended normal school and did not have a mentally retarded fraX relative, were selected to exclude influences of external factors. These subjects were submitted to an extensive neurocognitive and psychiatric evaluation before molecular analysis of their FMR-1 status was done to obtain completely unbiased results. The findings of this study suggest that differentiation according to the FMR-1 status may be more significant at the neurocognitive level than at the behavioral level and support the hypothesis that behavioral problems are more influenced by external factors than by the FMR-1 carrier state.

Molecular-intelligence correlations in young fragile X males with a mild CGG repeat expansion in the FMR1 gene.

Several mechanisms can explain the occurrence of full-mutation fragile X males with an IQ level above -2 SD below mean, also called "high-functioning fragile X males." Incomplete methylation of the CpG island at the 5' end of the FMR1 gene is one of these mechanisms. The present study describes the physical and behavior phenotypes in 7 fragile X boys with CGG repeat insertions in the FMR1 gene between 600-2,400 base pairs.

Temperament in Williams syndrome.

In this study we evaluated the temperament characteristics of a group of 13 subjects with Williams-Beuren syndrome (WBS) and compared the results to the findings in a control group of 13 individuals with the same degree of mental retardation of different etiology. On the different subscales of the Dutch adaptation of the Parent Temperament Questionnaire no statistically significant differences between the WBS and the control group were noted. An easier temperament was noted in the control group, and we also found greater intensity, less persistence and lower treshold in WBS subjects.

Fragile X boys: evolution of the mental age in childhood. Preliminary data on 10 prepubertal boys.

In this report we present data on the longitudinal evolution of the mental versus the chronological age in 10 fragile X boys diagnosed before the age of 6 years and compare these findings to the longitudinal evolution in children with Down syndrome (6 patients) and Williams syndrome (4 patients). The present findings suggest that the evolution of the velocity of development is more decreased in fra(x) boys compared to the two other groups.

Adults with Williams-Beuren syndrome: evaluation of the medical, psychological and behavioral aspects.

In order to evaluate the medical, psychological and behavioral aspects of Williams-Beuren syndrome in adulthood, data were collected on 11 patients aged 17 to 66 years. The medical data did not confirm previous reports of significant morbidity. All adults were found to have a moderate or severe degree of mental handicap.

Apparently enhanced visual information processing in female fragile X carriers: preliminary findings.

Eighteen normally intelligent adult female fragile X carriers were tested with the "de Sonneville Visual Attention Tasks," a computer-based set of reaction-time experiments, in order to assess different aspects of their attention capacity. The subject group was compared with a group of 48 adults, who were not known to be fragile X carriers. We publish preliminary results of this study.

Personality profile in adult female fragile X carriers: assessed with the Minnesota Multiphasic Personality Profile (MMPI).

To assess if the higher incidence of psychiatric morbidity in fragile X carriers is related to a particular pathological personality profile, we obtained a Minnesota Multiphasic Personality Profile from 11 normally intelligent (female) fragile X carriers. The sample mean for the clinical and validity scales all fell within the normal range. Although no pathological profile was found, some unexpected results emerged: low scores for the scales "schizophrenia" and "social introversion" and a so-called faking-good profile on the validity scales.