Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Constitutional obesity and mental retardation cooccur in several multiple congenital anomaly syndromes, including Prader-Willi syndrome, Bardet-Biedl syndrome, Cohen syndrome, Albright hereditary osteodystrophy, and Borjeson-Forssman-Lehmann syndrome as well as some rarer disorders. Although hypothalamic-pituitary axis abnormalities are thought to be a possible causative mechanism in some of these disorders, current knowledge is insufficient to explain the pathophysiologic mechanism of obesity in most multiple congenital anomaly/mental retardation syndromes. The chromosomal location of many of these syndromes is known, and studies are ongoing to identify the causative genes. Further delineation of the functions of the underlying genes will likely be instructive regarding mechanisms of appetite, satiety, and obesity in the general population. This review details current knowledge of the clinical and molecular genetic findings of multiple congenital anomaly/mental retardation syndromes associated with intrinsic obesity in an effort to delineate causative mechanisms and genetic abnormalities contributing to obesity.
 ...
PMID:Prader-Willi and other syndromes associated with obesity and mental retardation. 951 59

The article presents data concerning pseudohypoparathyroidism (PH TP). It is an unusual disease, which is characterized by the resistance of bones and kidney to PTH, followed by hypocalcaemia, hyperphospha-taemia, glandulary hypertrophy and hypersecretion of PTH. Patients with PTHT clinically manifest tetany seizures, soft tissue calcifications and many congenital malformations. The disease has a genetic etiology, it is connected with chromosome X and more often found in women. Clinical symptoms may be different and depend on genetic defect or its selectivity with reference to the tissues. At present we can distinguish three types of PHPT and pseudo-pseudo-HPT. The disease usually appears in the infancy. Early diagnosis and vitamin D3 or calcium treatment seem to be the most important for patient's condition. Too late treatment threatens with brain calcification followed by neurological defects and mental retardation. The long-lasting effect of PTH in bones can lead to their destruction, if bone receptors are completely sensitive.
 ...
PMID:[Pseudohypoparathyroidism]. 1090 70

Acrodysostosis is an uncommon skeletal dysplasia associated with nasal hypoplasia, midface deficiency, severe brachydactyly, and varying degrees of hearing loss and mental retardation. Previous publications have suggested that it may be difficult to distinguish acrodystostosis from pseudohypoparathyroidism on clinical grounds, but acrodysostosis does appear to have distinct clinical and radiologic findings. Spinal stenosis is an underappreciated risk in acrodysostosis, despite the reported loss of normal caudal widening of the lumbar interpediculate distance on AP spine radiographs in the original report of this disorder by Robinow et al., with confirmation of these radiographic findings by Butler et al. We report two sporadic cases of acrodysostosis, one of which required decompressive laminectomy for symptomatic spinal stenosis, and review 11 cases of acrodysostosis from 9 families that were submitted to the International Skeletal Dysplasia Registry. The objective of this report is to determine the frequency and severity of spinal stenosis in patients with acrodysostosis and to summarize the clinical and radiographic findings of acrodysostosis in an effort to distinguish acrodysostosis clearly from pseudohypoparathyroidism. The pattern of brachydactyly differs between these two conditions, and varying degrees of spinal stenosis are characteristic of acrodysostosis. Both our index patients with acrodysostosis had normal bioactivity of the alpha subunit of the Gs protein, therefore indicating that acrodysostosis has a different pathogenesis from pseudohypoparathyroidism. Furthermore, single-strand confirmational polymorphism (SSCP) analysis failed to demonstrate any confirmational alterations in the coding exons of the Gs alpha gene. These radiographic and laboratory findings substantiate that acrodysostosis is clinically different from pseudohypoparathyroidism and that it is necessary to follow patients with acrodysostosis for signs of spinal stenosis.
 ...
PMID:Radiographic findings and Gs-alpha bioactivity studies and mutation screening in acrodysostosis indicate a different etiology from pseudohypoparathyroidism. 1216 61

We report the case of a 27-year old woman who presented hypocalcemia and hyperphosphoremia during her first pregnancy. Her phenotype was in favor of Albright's hereditary osteodystrophy: short stature, obesity, round face, brachymetacarpy and mental retardation. However, the diagnosis of pseudohypopara thyroidism type Ia was ruled out due to low PTH level (10 pg/ml). The patient's 22q11 microdeletion was suspected and identified because of the association of severe neonatal hypocalcemia, abnormal face and renal malformation in her children. Deletion 22q11 leads to various syndromes, including Di George syndrome, also referred to as CATCH 22 syndrome (Cardiac defect (C), Abnormal face (A), Thymic hypoplasia (T), Cleft palate (C) and Hypocalcemia (H)). Retrospectively, the patient presented with symptoms suggestive of CATCH 22: abnormal face, hypernasal voice suggestive of velopharyngeal insufficiency, mental retardation, recurrent otitis in childhood. It is also noteworthy that there was an idiopathic thrombocytopenic purpura. In conclusion, while the phenotype was suggestive of Albright's hereditary osteodystrophy, the constatation of a low PTH level would cast doubt on this diagnosis. Furthermore, the 22q11 microdeletion should be searched by FISH (Fluorescence In Situ Hybridization) in all patients with hypopara thyroidism of unknown origin, even in the absence of cardiac malformations. Finally, it seems that patients with CATCH 22 would be predisposed to auto-immune disease as a result of thymic dysfunction.
 ...
PMID:[Pseudohypoparathyroidism or hypoparathyroidism? A misleading clinical presentation]. 1184 29

Albright hereditary osteodystrophy is a hereditary metabolic disorder of dominant autosomal etiology that is commonly characterized by short stature, round face, small metacarpus and metatarsus, mental retardation, osteoporosis, subcutaneous calcification, variable hypocalcemia, and hyperphosphatemia. In this study, we report a clinical case of a 17-year-old woman with Albright hereditary osteodystrophy, and we discuss her clinical, radiographic, and laboratory test characteristics together with the oral manifestations, and we correlate them with the characteristics found in the literature. We also discuss the odontological management of treatment of related periodontal disease and planning for corrections of related malocclusions.
 ...
PMID:Oral manifestations of Albright hereditary osteodystrophy: a case report. 1224 36

Albright hereditary osteodystrophy (AHO) results from heterozygous inactivation of G(s)alpha, encoded by the GNAS1 locus on the distal long arm of chromosome 20. This autosomal dominant condition is characterized by short stature, obesity, shortening of the metacarpals and metatarsals, and variable mental retardation and may also include end-organ resistance to multiple hormones. Small insertions and deletions or point mutations of GNAS1 are found in approximately 80% of patients with AHO. The remainder may be accounted for by larger genomic rearrangements, but none have been reported to date. We now describe two patients with constitutional 20q deletions and features of AHO. Such deletions are rare in the published literature and have not previously been associated with AHO. Molecular genetic analysis confirmed complete deletion of GNAS1 in both patients. Parental origin could be determined in both cases and provides further support for the parent-of-origin effect on the biochemical status of patients with AHO.
 ...
PMID:Constitutional deletion of chromosome 20q in two patients affected with albright hereditary osteodystrophy. 1240 7

Genetic analysis of the GNAS gene was performed in a patient with idiopathic renin-dependent hypertension, PTH resistance, and Albright's hereditary osteodystrophy-like characteristics such as a round face, short stature, obesity, and mental retardation (IQ, 49). Mutational analysis showed no mutations in exons 1-13 or in any exon-intron boundary. However, methylation-status analysis revealed a bialleic methylation defect in GNAS exon 1A, indicating that a GNAS-imprinting defect is the cause of her PTH resistance, as commonly observed in pseudohypoparathyroidism type IB. The imprinting defect, however, could not explain her renin-dependent hypertension and Albright's hereditary osteodystrophy-like phenotype. There are many types of X-linked mental retardation. Syndromic X-linked mental retardation, such as X-linked alpha-thalassemia mental retardation syndrome and Rett syndrome, is reportedly associated with abnormal imprinting. To further investigate this unexplained phenotype, we tested whether this patient showed skewed X-inactivation (SXI) presumably as a result of postinactivation selection against cells with a mutated gene on the active X-chromosome. Completely SXI was observed in the DNA from her leukocytes, urinary sediment, and renal tissue. A mutation of the X-chromosome might be correlated with this phenotype because of a close association between completely SXI and X-chromosomal mutation.
 ...
PMID:Completely skewed X-inactivation in a mentally retarded young female with pseudohypoparathyroidism type IB and juvenile renin-dependent hypertension. 1284 41

We here describe a submicroscopic translocation affecting the subtelomeric regions of chromosomes 2q and 6q identified in a patient referred to us because of mental retardation, obesity, brachydactyly, and short stature. FISH analysis using subtelomeric probes showed a 46,XY,der(2)t(2;6)(q37.3;q26) in the propositus, and a balanced t(2;6) in his father and sister. FISH with region-specific genomic clones made it possible to map the 2q37.3 breakpoint precisely to the region covered by BAC 585E12, and the 6q26 breakpoint to between the regions encompassed by 414A5 and 480A20. The 2q subtelomeric deletion has often been found in patients with Albright hereditary osteodystrophy (AHO)-like syndrome but, to the best of our knowledge, the 2q37.3-qter monosomy ascertained in our patient is the smallest so far described within the syndrome's critical interval, and may thus enhance the search for the responsible genes.
 ...
PMID:Narrowing the candidate region of Albright hereditary osteodystrophy-like syndrome by deletion mapping in a patient with an unbalanced cryptic translocation t(2;6)(q37.3;q26). 1296 29

About 2-3% of "essential" obesity in pediatric age is of endocrine or genetic origin (secondary obesity). The clinical picture of these forms is almost always characteristic; however, some patients affected by secondary obesity can present with an incomplete or atypical aspect. The aim of this review is to offer the pediatrician useful indications to correctly diagnose children presenting with obesity. It is advisable to make a careful anamnesis and an accurate medical examination in order to ascertain the causes that may have contributed to the onset and increase of weight gain. Obesity associated with mental retardation, short stature, cryptorchidism or hypogonadism, dysmorphism with facies sui generis, ocular or uditive defects, might suggest a genetic origin. Prader-Willi syndrome is the most frequent of these disorders and it is due to an alteration of chromosome 15 of paternal origin. These patients have to undergo the methilation test (easy and low cost genetic research) in order to confirm the clinical suspicion. Endocrine alterations, that play a pathogenic role in pediatric obesity (i.e., hypothyroidism, hypothalamic-pituitary diseases, pseudohypoparathyroidism), are rare. Early treatment of hormonal dysfunction generally allows to ameliorate or normalize the weight gain. In absence of specific clinical manifestations or lacking a significant clinical history, no endocrine test is required. The family pediatrician should require some routine hematochimic tests, in order to evaluate the possible presence of hyperlipidemia and/or glycometabolic complications. An oral glucose tolerance test is necessary only for patients presenting with serious weight gain, acanthosis nigricans, and for those with a family history of diabetes. In the most serious cases, a careful cardiovascular and respiratory evaluation should be performed. Children with a suspicion of secondary obesity have to be submitted to an endocrinologist, for a correct diagnosis and a specific treatment. However, the family pediatrician's assistance is essential during the follow-up period, in order to assure the patient and his/her family a proper assistance.
 ...
PMID:[Diagnosis and differential diagnosis of obesity in childhood]. 1460 69

The Albright hereditary osteodystrophy-like (AHO-like) syndrome was recently defined as a rare dysmorphic syndrome including brachymetaphalangism and mental retardation. This phenotype occurs in Albright hereditary osteodystrophy (AHO) but unlike it, the level of the Gs alpha protein activity is not reduced. To date 59 patients with these clinical and biochemical features have been reported, and for the majority of them (57/59) a cytogenetically visible 2q37 deletion has been observed. We report a new case of typical AHO-like syndrome with normal karyotype. Using the polymorphic marker D2S125 we found a loss of heterozygosity suggestive of a de novo 2q37 deletion of maternal origin. This hypothesis was confirmed by FISH analysis with a subtelomeric 2q probe containing the D2S90 marker. Genotypic analysis allowed us to map the proximal breakpoint of the subtelomeric deletion within an interval delimited by D2S2338 (present) and D2S2253 (deleted). This 2q subtelomeric deletion as small as 4 Mb is to date the smallest one observed in association with a typical AHO-like phenotype, and allows us to move the centromeric boundary of the AHO-like critical region by 750 kb towards the 2q telomere.
 ...
PMID:Molecular characterization of a cryptic 2q37 deletion in a patient with Albright hereditary osteodystrophy-like phenotype. 1526 88


<< Previous 1 2 3 4 5 Next >>