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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this report we describe two fra(X) adults and two prepubertal fra(X) brothers with a combination of distinct phenotypic findings: extreme obesity, short stature, stubby hands and feet and diffuse hyper-pigmentation. These clinical abnormalities may be an additional indication of a specific hypothalamic disturbance in the fra(X) syndrome.
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PMID:A peculiar subphenotype in the fra(X) syndrome: extreme obesity-short stature-stubby hands and feet-diffuse hyperpigmentation. Further evidence of disturbed hypothalamic function in the fra(X) syndrome? 343 88

Four boys aged 6-16 years with neurodevelopmental deficits were treated with CPAP for obstructive sleep apnoea. Their diagnoses were: Obesity with mild mental retardation, (2) attention deficit hyperactivity disorder, (3) epilepsy associated with left hemiparesis and (4) mild mental retardation due to fragile X syndrome. Previous therapeutic attempts, including adenotonsillectomy, amitriptyline and methylphenidate in our patients prior to CPAP treatment were unsuccessful. A follow-up period of 12-48 months demonstrated a number of clinical benefits such as improvement in sleep quality and daily arousal, and a decrease in the frequency of seizures and episodes of pneumonia. Polysomnographic studies indicated a significant improvement in sleep parameters such as apnoea frequency, awakenings, sleep efficiency and arterial oxygen saturation. Side effects were mild and readily alleviated. CPAP is a feasible therapeutic intervention in intractable obstructive sleep apnoea of childhood, even when associated with neurodevelopmental deficits.
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PMID:CPAP treatment of obstructive sleep apnoea and neurodevelopmental deficits. 754 99

Fragile X syndrome is the most common form of inherited mental retardation and results from the transcriptional inactivation of the FMR1 gene. In the vast majority of cases, this is caused by the expansion of an unstable CGG repeat in the first exon of the FMR1 gene. We describe here a phenotypically atypical case of fragile X syndrome, caused by a deletion that includes the entire FMR1 gene and > or = 9.0 Mb of flanking DNA. The proband, RK, was a 6-year-old mentally retarded male with obesity and anal atresia. A diagnosis of fragile X syndrome was established by the failure of RK's DNA to hybridize to a 558-bp PstI-XhoI fragment (pfxa3) specific for the 5'-end of the FMR1 gene. The analysis of flanking markers in the interval from Xq26.3-q28 indicated a deletion extending from between 160-500 kb distal and 9.0 Mb proximal to the FMR1 gene. High-resolution chromosome banding confirmed a deletion with breakpoints in Xq26.3 and Xq27.3. This deletion was maternally transmitted and arose as a new mutation on the grandpaternal X chromosome. The maternal transmission of the deletion was confirmed by FISH using a 34-kb cosmid (c31.4) containing most of the FMR1 gene. These results indicated that RK carried a deletion of the FMR1 region with the most proximal breakpoint described to date. This patient's unusual clinical presentation may indicate the presence of genes located in the deleted interval proximal to the FMR1 locus that are able to modify the fragile X syndrome phenotype.
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PMID:An atypical case of fragile X syndrome caused by a deletion that includes the FMR1 gene. 772 57

A 3-year-old boy was referred to the pediatric department because of unexplained extreme obesity. Height and occipitofrontal circumference were just above the 90th centile. Endocrine studies failed to show any significant abnormality. Motor and speech development were generally delayed. On clinical-cytogenetic-molecular grounds, Prader-Willi syndrome was excluded. Fragile X syndrome was diagnosed by the presence of the classical FMR-1 mutation and confirmed by cytogenetic studies, revealing 20% fragile X positive cells. We compare the clinical features in the present patient with the nine reported patients with fra(X) syndrome and extreme obesity. In pathogenesis, hypothalamic dysregulation is hypothesized. In differential diagnosis of Prader-Willi syndrome, fragile X has to be considered, especially when laboratory workup for Prader-Willi syndrome is negative. Clinical behavior can be of help.
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PMID:Prader-Willi-like phenotype in fragile X syndrome. 806 34

A special subphenotype of the fragile X syndrome is reported which is characterised by extreme obesity with a full, round face, small, broad hands/feet, and regional skin hyperpigmentation. It resembles the Prader-Willi syndrome (PWS) and might therefore be named 'Prader-Willi-like'. Unlike the PWS, these PW-like fragile X patients lack the neonatal hypotonia with feeding problems during infancy followed by hyperphagia from toddlerhood. We describe five new fragile X patients and present a clinical update of three previously described patients with the PW-like phenotype. In one family, segregation of either the classical Martin-Bell or the PW-like phenotype was observed and in another family there was repeated transmission of the PW-like phenotype. Previously, one of the patients had been misdiagnosed as having classical PWS, based on clinical findings. Molecular studies of the FMR-1 gene showed the typical full mutations as seen in fragile X syndrome males. Molecular analysis of the 15q11-13 region, which is deleted in the majority of classical PWS patients, did not show any detectable abnormalities. In a group of 26 patients with suspected Prader-Willi syndrome but without detectable molecular abnormalities of chromosome 15, one fragile X patient was found. These clinical and molecular findings illustrate the necessity to perform DNA analysis of the FMR-1 gene in mentally retarded patients presenting with a PW phenotype but without the PWS specific cytogenetic/molecular abnormalities of chromosome 15.
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PMID:Clinical and molecular studies in fragile X patients with a Prader-Willi-like phenotype. 801 84

A four-year-old boy with severe psychomotor retardation, facial appearance consistent with the fragile X syndrome, hypotonia, and overgrowth was found to have a deletion including the fragile X gene (FMR1). The breakpoints of the deletion were established between CDR1 and sWXD2905 (approximately 200 kb apart) at Xq27.1 (centromeric) and between DXS8318 (612-1078L) and DXS7847 (576-291L) (approximately 250 kb apart) at Xq28, about 500 kb telomeric to the FMR1 gene. The total length of the deletion is approximately 8.5 Mb. The propositus's mother, who was found to be a carrier of the deletion, showed very mild mental impairment. Except for mental retardation, which is a common finding in all cases reported with similar deletions of chromosome Xq, this patient had generalized overgrowth, exceeding the 97th centile for height and weight. Obesity and increased growth parameters have been reported in other patients with deletions either overlapping or within a distance of 0.5 Mb from the deletion in the present patient. Thus, it is suggested that a deletion of the 8-Mb fragment centromeric to the FMR1 gene might have an effect on growth.
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PMID:Deletion of 8.5 Mb, including the FMR1 gene, in a male with the fragile X syndrome phenotype and overgrowth. 1020 66

We report a novel X-linked mental retardation (XLMR) syndrome, with characteristic facial dysmorphic features, segregating in a large North Carolina family. Only males are affected, over four generations. Clinical findings in the seven living affected males include a moderate degree of mental retardation (MR), coarse facies, puffy eyelids, narrow palpebral fissures, prominent supraorbital ridges, a bulbous nose, a prominent lower lip, large ears, obesity, and large testicles. Cephalometric measurements suggest that the affected males have a distinctive craniofacial skeletal structure, when compared with normative measures. Obligate-carrier females are unaffected with MR, but the results of cephalometric skeletal analysis suggest craniofacial dysmorphisms intermediate between affected males and normative control individuals. Unaffected male relatives show no clinical or cephalometric resemblance to affected males. The blood-lymphocyte karyotype and the results of DNA analysis for fragile-X syndrome and of other routine investigations are normal. Linkage analysis for polymorphic DNA markers spanning the X chromosome established linkage to Xq26-q27. Maximum LOD scores were obtained at marker DXS1047 (maximum LOD score = 3.1 at recombination fraction 0). By use of haplotype analysis, we have localized the gene for this condition to an 18-cM genetic interval flanked by ATA59C05 and GATA31E08. On the basis of both the clinical phenotype and the mapping data, we were able to exclude other reported XLMR conditions. Therefore, we believe that a unique recessive XLMR syndrome with a distinctive and recognizable phenotype is represented in this family.
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PMID:A unique form of mental retardation with a distinctive phenotype maps to Xq26-q27. 1067 7

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.
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PMID:Problems in the diagnosis of fragile X syndrome in young children are still present. 1129 71

We report on a 34-year-old developmentally disabled man referred to our clinic for evaluation of possible Prader-Willi syndrome on the basis of obesity and voracious appetite. Cytogenetic and molecular analysis revealed a 47, XYY karyotype and the presence of a trinucleotide repeat expansion resulting in fragile X syndrome. To our knowledge, this is the first report of concurrence of XYY and fragile X syndrome in the medical literature. Review of sex chromosome abnormalities associated with fragile X syndrome and phenotypic considerations are presented.
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PMID:Concurrence of fragile X syndrome and 47, XYY in an individual with a Prader-Willi-like phenotype. 1249 38

Evidence is reviewed that the consequences of group 1 metabotropic glutamate receptor (Gp1 mGluR) activation are exaggerated in the absence of the fragile X mental retardation protein, likely reflecting altered dendritic protein synthesis. Abnormal mGluR signaling could be responsible for remarkably diverse psychiatric and neurological symptoms in fragile X syndrome, including delayed cognitive development, seizures, anxiety, movement disorders and obesity.
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PMID:Therapeutic implications of the mGluR theory of fragile X mental retardation. 1609 37


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