1/14. Identification and evaluation of mental retardation.Mental retardation in young children is often missed by clinicians. The condition is present in 2 to 3 percent of the population, either as an isolated finding or as part of a syndrome or broader disorder. Causes of mental retardation are numerous and include genetic and environmental factors. In at least 30 to 50 percent of cases, physicians are unable to determine etiology despite thorough evaluation. Diagnosis is highly dependent on a comprehensive personal and family medical history, a complete physical examination and a careful developmental assessment of the child. These will guide appropriate evaluations and referrals to provide genetic counseling, resources for the family and early intervention programs for the child. The family physician is encouraged to continue regular follow-up visits with the child to facilitate a smooth transition to adolescence and young adulthood.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
2/14. Monozygotic boys with fragile x syndrome.Monozygotic twin boys with fragile x syndrome underwent thorough genetic, psychiatric, neurological, and language evaluations at 10 years of age. They both demonstrated physical features, speech and language difficulties, social problems, and attentional deficits that characterize the behavioural phenotype of fragile x syndrome. Despite identical genetic constitutions, there were important developmental and behavioural heterogeneities. Twin A showed less social interaction and symbolic play and more speech and language dysfunction than twin B. Twin A also had significantly larger caudate volumes. It is suggested that the Xq27.3 anomaly may not be sufficient to account for all the behavioural phenotypic and neuroanatomical features of fragile x syndrome.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
3/14. Problems in the diagnosis of fragile x syndrome in young children are still present.fragile x syndrome is common; its prevalence approaches 1 per 5,000. fragile x syndrome is the most common inherited cause of mental retardation. Many professionals must deal with fragile X individuals on a daily basis. However, despite the diverse information on the epidemiology, clinical features, unique pattern of inheritance, cytogenetic, and molecular diagnosis and scales for the diagnosis of this syndrome, the diagnosis of fragile x syndrome is still not always made by the patients' specialists. Here we present the difficulties in the diagnosis of fragile x syndrome in 11 children under 8 years of age, 10 boys and one girl. We report data on initial symptoms, behavioral features, and physical and mental development before molecular studies were considered. The possible causes for the diagnosis delay were multiple: nonspecific features (e.g., macrocephaly, overgrowth, obesity), unremarkable physical examination, family history apparently noncontributory, and lack of or delayed molecular testing. Careful clinical examination of young children and dna screening in case of doubt, and education of professionals in medical specialty areas, behavioral sciences, education, and other fields are recommended.- - - - - - - - - - ranking = 2keywords = physical (Clic here for more details about this article) |
4/14. Fragile site Xq27.3 in a family without mental retardation.Routine parental blood analysis for a couple undergoing prenatal diagnosis because of maternal age, revealed a 47,XXX karyotype in the mother and expression of the fragile site Xq27.3 in the father. Additional family studies show the fragile site in the father's sister and her two sons. There is no history of intellectual handicap in this family, nor of any physical manifestations of the Fra(X) mental retardation syndrome.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
5/14. mosaicism for a full mutation, premutation, and deletion of the CGG repeats results in 22% FMRP and elevated FMR1 mRNA levels in a high-functioning fragile X male.The molecular basis in the majority of fragile X patients results from expansion of the CGG repeats in the FMR1 gene causing its transcriptional silencing and deficiency of its encoded protein FMRP. In this communication, we report on a male patient who lacks the characteristic physical features of fragile X and carries a fully methylated mutation, a premutation, a non-methylated full mutation, and a microdeletion encompassing the entire CGG repeat region and 42 bp of upstream flanking sequence. Southern blot analysis revealed that the methylated full mutation accounted for only 10% of his genotype while the premutation/non-methylated full mutation and the microdeletion constituted 37% and 53%, respectively. Immunofluorescent staining of FMRP demonstrated the presence of 22% FMRP in his peripheral blood leukocytes and quantitative RT-PCR revealed a 3.6-fold elevation of FMR1 mRNA levels. Developmental assessments indicated that while he has a learning disability, he does not have mental retardation. Because previous reports had noted that 28% FMRP expression is associated with a characteristic fragile X phenotype, we propose that in our patient the association of 22% FMRP levels with normal physical features and a high-functioning status may have resulted from increased FMRP stability by a mechanism that takes into account the CGG microdeletion and elevated mRNA levels.- - - - - - - - - - ranking = 2keywords = physical (Clic here for more details about this article) |
6/14. Autism in association with fragile x syndrome in females: implications for diagnosis and treatment in children.fragile x syndrome is the second most common chromosomal cause of mental retardation (MR). The calculated incidence is 1/1000, making accurate and early diagnosis important for specific preventive, pharmacologic, and cognitive treatment. The timely diagnosis in males is facilitated by the characteristic phenotype and an association with autism. In contrast, in females heterozygous for fragile X, the characteristic phenotype and infantile autism are rarely reported. We present two females with cytogenetic expression of the fragile x chromosome for whom the studies were performed because of the presence of autism or prominent autistic features and a behavioral and physical phenotype consistent with fragile x syndrome. The first female, age three years, has autism, hyperactivity, echolalia, language delay, hand stereotypies, and mild MR. The characteristic phenotype was not present nor was there a family history of X-linked MR. Fragile X expression was 6% in the proband, 3% in the mother and 1% (normal) in the father. The second child, seven years old, has prominent autistic features, hyperactivity, mild MR, mild language disorder, and a family history consistent with X-linked MR. Fragile X expression was 3% in the proband and 0% in the mother. These cases support the occurrence of fragile X in autistic females and emphasize the importance of cytogenetic screening for fragile X in this high risk population. early diagnosis of fragile X allows precise genetic counseling and more specific cognitive and pharmacologic treatment.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
7/14. klinefelter syndrome and associated fragile-X syndrome.During screening of male individuals for Fragile-X syndrome in a residential facility for persons with mental retardation, the authors found a 21-year-old profoundly retarded man who displayed facial features and behaviour suggestive of Fragile-X syndrome. The chromosome analysis revealed 47,fra(X)(q27)fra(X)(q27)Y. His physically and intellectually normal sister had 14% of X chromosomes with a fragile site. Her two sons, who were subsequently examined, were found to have Fragile-X syndrome. Thus, the identification of Fragile-X syndrome in the proband during the screening process of a large institution led to the investigation of the proband's family and the subsequent diagnosis of Fragile-X syndrome in the proband's two nephews. The ascertainment of the two affected boys permitted prompt introduction of early intervention and special education services. Genetic counselling of other at-risk family members was carried out.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
8/14. Cognitive and psychiatric variability in three brothers with fragile x syndrome.Three brothers were determined to have the fragile x syndrome. While sharing physical characteristics, their developmental and behavioral characteristics were diverse, as was the severity of the disorder. Each brother had evidence of developmental problems but demonstrated heterogeneity of presentation in the same sibship.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
9/14. learning disabilities and attentional problems in boys with the fragile x syndrome.The fragile x syndrome is a relatively common form of mental retardation that tends to affect boys more severely than girls. The syndrome is associated with a fragile site at q27 on the x chromosome and with physical features including large or prominent ears and macro-orchidism. Four boys had physical and cytogenetic features of the fragile x syndrome. However, the IQ scores of these patients extended into the normal range. All four patients demonstrated similar learning difficulties that included hyperactivity, visuomotor incoordination, language deficits, and academic delays in mathematics. The fragile x syndrome should be considered in the differential diagnosis of learning disabled children.- - - - - - - - - - ranking = 2keywords = physical (Clic here for more details about this article) |
10/14. Identical triplets with infantile autism and the fragile-X syndrome.In a continuing twin study of autism in scandinavia and finland, moderately mentally retarded triplets fulfilling Rutter's criteria for infantile autism were reported. Judging by physical appearance the triplets were identical. Behaviourally they were extremely similar though one was intellectually slightly better than the other two. All three showed the physical stigmata characteristic of the fragile-X syndrome, in spite of their overall appearance being non-conspicuous. The triplets had between 8 and 12 per cent of fragile-X positive cells and showed a distinct pattern of urinary excretion of substances yielding absorbency at 280 nM. Their mother and sister also had a high count of fragile-X positive cells.- - - - - - - - - - ranking = 2keywords = physical (Clic here for more details about this article) |
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