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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report describes twin girls with typical features of ataxia-telangiectasia, including increased alpha-fetoprotein, radio-resistant DNA synthesis, characteristic chromosome abnormality, and immunodeficiency. They have, in addition, microcephaly and mental retardation. Complementation studies were performed utilizing Sendai virus--mediated fusion of fibroblast cell lines. Complementation was observed with patients in ataxia-telangiectasia complementation groups A, C, and E but not with the cell line from a patient with the Nijmegen breakage syndrome, in which patients have microcephaly, radio-resistant DNA synthesis, chromosome aberrations, and immunodeficiency but lack ataxia and telangiectasia. These data suggest that the Nijmegen breakage syndrome and the patients described here are not genetically distinct entities but form a spectrum of one disorder.
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PMID:ATFresno: a phenotype linking ataxia-telangiectasia with the Nijmegen breakage syndrome. 249 Nov 81

Down's syndrome is the most common autosomal aberration and single cause of mental retardation in man. There is a close relation between advanced maternal age and Down's syndrome. The limitation of family size has made a considerable impact on the incidence of Down's syndrome. In Denmark in the 1950s, 50% of Down's syndrome cases were born to mothers over the age of 35. The percentage went down to 25% in the 1970s and was reduced by prenatal diagnosis to 8% in the 1980s. For the period 1980-85 we followed the birth prevalence closely for different maternal age groups. The birth prevalence was lowered for the age group over 35, but there was a steady rise for the age groups below 35. Early diagnosis, high rate of survival of light-for-date babies and babies with congenital heart defect, and, possibly, exogenous factors working on gametogenesis might be an explanation. To achieve a reduction in incidence, maternal alpha-fetoprotein (AFP)-serum screening for low values may be a possibility. So far, avoidance, but not primary prevention, of Down's syndrome is available.
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PMID:The incidence of Down's syndrome and progress towards its reduction. 290 May 25

The authors report a 9-year-old girl with mid-facial hypoplasia, maxillary hypoplasia, prognathia, microbrachycephaly, mouth opening and protruding tongue. She also had psychomotor retardation such as mental retardation and speech delay. Frequent laughter fits and seizure disorder was also noted. Although the high resolution chromosome study failed to demonstrate any deletion of chromosome 15q, the clinical picture was compatible with Angelman syndrome. Breast development at the age of six and rapid progression of bone age was noted at follow up. After a series of examinations, the diagnosis of gonadotropin-dependent precocious puberty was made. MRI of brain revealed an intermediate cyst in the pituitary gland and slightly enlarged pineal gland. However, serum alpha-fetoprotein and beta-HCG were undetectable and the size of the pineal gland remained the same at the 1-year follow-up. She was treated with long-acting GnRH analogue and valproic acid. The combination of precocious puberty and Angelman syndrome has not been reported before and such association needs further experience for clarification.
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PMID:Precocious puberty in a case with probable Angelman syndrome. 794 14

We reviewed genetics charts of 2235 patients seen from 1985 to 1990 at Vanderbilt University Medical Center, Nashville, Tennessee, and summarized the 20 most common reasons for referral (occurring in 1138 of the patients) and the diagnoses or conditions among patients receiving genetic services in one of four clinical settings (prenatal counseling clinics, general genetics clinics, outreach genetics clinics, and ward consultations). The five most common reasons for referral were advanced maternal age (> or = 35 years) (203/1138, or 18% of patients), followed by dysmorphic features/multiple congenital anomalies (MCA) (185/1138; 16%), developmental delay/mental retardation (MR) (168/1138; 15%), Down's syndrome (103/1138; 9%), and abnormal maternal serum alpha-fetoprotein (MSAFP) (74/1138; 7%). The five most common diagnoses or conditions identified for all genetics patients were advanced maternal age (> or = 35 years) (195/906; 22%), developmental delay/MR (111/906; 12%), dysmorphic features/MCA (107/906; 12%), Down's syndrome (88/906; 10%), and multiple fetal losses (57/906; 6%). Of the 20 most common diagnoses or conditions categorized in 602 of the 906 patients, a multifactorial cause was observed in 25% of those patients; a chromosomal cause was observed in 26% of cases of Down's syndrome, accounting for 55% of the chromosomal disorders; a single gene disorder was observed in 17% of patients; an environmental cause was seen in 4%; and an unknown cause was noted in 28%. We hope this study will help physicians in middle Tennessee and surrounding areas by increasing their awareness of the types and frequencies of genetic diseases so that misdiagnoses and delayed referrals can be avoided.
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PMID:Genetic conditions among patients receiving genetic services in middle Tennessee. 842 15

Down syndrome is one of the most common causes of mental retardation in the industrialized world. Prenatal serum screening to identify mothers at risk of carrying a fetus affected with Down syndrome is presently part of routine obstetrical care. Prostate-specific antigen (PSA) concentration was measured in stored second-trimester maternal serum samples from 19 pregnancies affected with fetal Down syndrome and in 95 samples from unaffected pregnancies, with each case matched to five controls for gestational age and duration of frozen sample storage. Concentrations of PSA in Down syndrome pregnancy were significantly higher (case median = 2.28 multiples of the median; P = 0.02) than in unaffected pregnancy. PSA concentrations were not significantly correlated with the current serum screening analytes, alpha-fetoprotein, unconjugated estriol, or human chorionic gonadotropin in either cases or controls. The increased maternal serum PSA concentrations in Down syndrome pregnancy and their relative independence from other markers suggest the possible utility of PSA as a prenatal screening marker for fetal Down syndrome.
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PMID:Increased concentrations of prostate-specific antigen in maternal serum from pregnancies affected by fetal Down syndrome. 947 12

Down syndrome (trisomy 21) is the most commonly recognized genetic cause of mental retardation. The risk of trisomy 21 is directly related to maternal age. All forms of prenatal testing for Down syndrome must be voluntary. A nondirective approach should be used when presenting patients with options for prenatal screening and diagnostic testing. Patients who will be 35 years or older on their due date should be offered chorionic villus sampling or second-trimester amniocentesis. Women younger than 35 years should be offered maternal serum screening at 16 to 18 weeks of gestation. The maternal serum markers used to screen for trisomy 21 are alpha-fetoprotein, unconjugated estriol and human chorionic gonadotropin. The use of ultrasound to estimate gestational age improves the sensitivity and specificity of maternal serum screening.
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PMID:Down syndrome: prenatal risk assessment and diagnosis. 1096 55

We performed molecular analysis of a germline interstitial deletion of chromosome 4 [del(4)(q21.22q23)], which had been observed in a male infant manifesting early-onset hepatoblastoma (HBL). The chromosomal anomaly in this child was associated with a unique congenital syndrome including HBL, atrial septal defect, ventricular septal defect, patent ductus arteriosus, mental retardation, and seizures. However, the patient did not exhibit a megalencephaly typical of 4q21-22 deletions. His HBL was associated with an increasing serum alpha-fetoprotein level and rapid growth. To define the chromosomal deletion at the molecular level in this child, we analyzed his lymphoblasts with fluorescence in situ hybridization, using as probes a panel of BAC/PAC genomic clones containing STS markers covering the 4q12-27 region. The analysis revealed that the affected chromosome had an 8-cM deletion within 4q21-q22, flanked by markers D4S2964 and D4S2966. This microdeletion overlaps with the commonly deleted region at 4q21-q22 that was recently defined in adult hepatocellular carcinomas.
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PMID:An 8-cM interstitial deletion on 4q21-q22 in DNA from an infant with hepatoblastoma overlaps with a commonly deleted region in adult liver cancers. 1156 28

Ataxia-telangiectasia is a multisystem disorder characterized by progressive neurologic impairment, variable immunodeficiency, impaired organ maturation, x-ray hypersensitivity, oculocutaneous telangiectasia, and a predisposition to malignancy. To evaluate clinical and immunologic features of Iranian patients with ataxia-telangiectasia, the records of 104 patients with ataxia-telangiectasia (54 male, 50 female) with the age range of 1.6-23.5 years were reviewed. The Iranian Primary Immunodeficiency Registry was used as the data source. Progressive ataxia was seen in all the patients. Other symptoms were eye movement disorders (n = 84), slurred speech (n = 70), mental retardation (n = 10), and ocular (n = 87) and cutaneous (n = 73) telangiectasia. Three patients developed leukemia and lymphoma, and 17 patients had family history of malignancy. Positive correlation was seen between clinical immunologic symptoms and immunoglobulin deficiencies (P = 0.004). The predominant infections were sinopulmonary and acute and recurrent infections (78 cases). Infections included pneumonia (56 patients), otitis media (34 patients), and sinusitis (50 patients). Average serum alpha-fetoprotein level was 149 +/- 137 ng/dL. The incidence of ataxia-telangiectasia in Iran is high, possibly due to familial marriages. Treatment should be focused on supportive management to prolong survival.
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PMID:Ataxia-telangiectasia in Iran: clinical and laboratory features of 104 patients. 1762 18

Human alpha-fetoprotein is a pregnancy-associated protein with an undetermined physiological role. As human alpha-fetoprotein binds retinoids and inhibits estrogen-dependent cancer cell proliferation, and because retinoic acid (a retinol metabolite) and estradiol (an estrogen) can both initiate cellular gene transcription, it is hypothesized here that alpha-fetoprotein functions during critical gestational periods to prevent retinoic acid and maternal estradiol from inappropriately stimulating gene expression in developing brain regions which are sensitive to these chemicals. Prenatal/maternal factors linked to increased autism risk include valproic acid, thalidomide, alcohol, rubella, cytomegalovirus, depression, schizophrenia, obsessive-compulsive disorder, autoimmune disease, stress, allergic reaction, and hypothyroidism. It will be shown how each of these risk factors may initiate expression of genes which are sensitive to retinoic acid and/or estradiol - whether by direct promotion or by reducing production of alpha-fetoprotein. It is thus hypothesized here that autism is not a genetic disorder, but is rather an epigenetic disruption in brain development caused by gestational exposure to chemicals and/or conditions which either inhibit alpha-fetoprotein production or directly promote retinoic acid-sensitive or estradiol-sensitive gene expression. This causation model leads to potential chemical explanations for autistic brain morphology, the distinct symptomatology of Asperger's syndrome, and the differences between high-functioning and low-functioning autism with regard to mental retardation, physical malformation, and sex ratio. It will be discussed how folic acid may cause autism under the retinoic acid/estradiol model, and the history of prenatal folic acid supplementation will be shown to coincide with the history of what is popularly known as the autism epidemic. It is thus hypothesized here that prenatal folic acid supplementation has contributed to the post-1980 increase in US autism diagnoses. In addition to explaining the epidemic within the wider retinoic acid/estradiol model of causation, this theory leads to potential explanations for certain genetic findings in autism, autistic regression, and changing trends in autism symptomatology with regard to mental retardation, wheat allergy, and gastrointestinal problems.
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PMID:A novel embryological theory of autism causation involving endogenous biochemicals capable of initiating cellular gene transcription: a possible link between twelve autism risk factors and the autism 'epidemic'. 2138 46