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

Germline mutations in the tumour suppressor gene PTEN have been implicated in two hamartoma syndromes that exhibit some clinical overlap, Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRR). PTEN maps to 10q23 and encodes a dual specificity phosphatase, a substrate of which is phosphatidylinositol 3,4,5-triphosphate, a phospholipid in the phosphatidylinositol 3-kinase pathway. CS is characterized by multiple hamartomas and an increased risk of benign and malignant disease of the breast, thyroid and central nervous system, whilst the presence of cancer has not been formally documented in BRR. The partial clinical overlap in these two syndromes is exemplified by the hallmark features of BRR: macrocephaly and multiple lipomas, the latter of which occur in a minority of individuals with CS. Additional features observed in BRR, which may also occur in a minority of CS patients, include Hashimoto's thyroiditis, vascular malformations and mental retardation. Pigmented macules of the glans penis, delayed motor development and neonatal or infant onset are noted only in BRR. In this study, constitutive DNA samples from 43 BRR individuals comprising 16 sporadic and 27 familial cases, 11 of which were families with both CS and BRR, were screened for PTEN mutations. Mutations were identified in 26 of 43 (60%) BRR cases. Genotype-phenotype analyses within the BRR group suggested a number of correlations, including the association of PTEN mutation and cancer or breast fibroadenoma in any given CS, BRR or BRR/CS overlap family ( P = 0.014), and, in particular, truncating mutations were associated with the presence of cancer and breast fibroadenoma in a given family ( P = 0.024). Additionally, the presence of lipomas was correlated with the presence of PTEN mutation in BRR patients ( P = 0.028). In contrast to a prior report, no significant difference in mutation status was found in familial versus sporadic cases of BRR ( P = 0.113). Comparisons between BRR and a previously studied group of 37 CS families suggested an increased likelihood of identifying a germline PTEN mutation in families with either CS alone or both CS and BRR when compared with BRR alone ( P = 0.002). Among CS, BRR and BRR/CS overlap families that are PTEN mutation positive, the mutation spectra appear similar. Thus, PTEN mutation-positive CS and BRR may be different presentations of a single syndrome and, hence, both should receive equal attention with respect to cancer surveillance.
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PMID:PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome. 1040 Sep 93

PTEN/MMACI/TEP1, a tumor suppressor gene located on 10q23.3, encodes an almost ubiquitously expressed dual-specificity phosphatase. Germline mutations in PTEN have been found in the majority of cases of sporadic and familial Cowden syndrome (CS), an autosomal dominant inherited cancer syndrome characterised by multiple hamartomas and benign and malignant disease of the thyroid and breast. Interestingly, germline mutations in PTEN have also been found in about 50% of a related but distinct disorder, Bannayan-Ruvalcaba-Riley syndrome (BRR), which is characterised by neonatal-onset macrocephaly, mental retardation, Hashimoto's thyroiditis, lipomatosis, haemangiomas, hamartomatous polyps, and pigmented macules of the glans penis. Somatic PTEN mutation has been described to a greater or lesser extent in various benign and malignant tumor types. Somatic deletions have been described in follicular adenomas of the thyroid and papillary thyroid carcinomas.
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PMID:The role of PTEN, a phosphatase gene, in inherited and sporadic nonmedullary thyroid tumors. 1054 86

Iodine deficiency is the most common cause of hypothyroidism worldwide. In persons living in iodine-replete areas, causes are congenital, spontaneous because of chronic autoimmune disease (atrophic autoimmune thyroiditis or goitrous autoimmune thyroiditis [Hashimoto's thyroiditis]), or iatrogenic because of goitrogens, drugs, or destructive treatment for thyrotoxicosis. Screening for congenital hypothyroidism exists and its use prevents mental retardation. The prevalence of spontaneous hypothyroidism is between 1% and 2% and is more common in older women and 10 times more common in women than in men. A significant proportion of subjects have asymptomatic chronic autoimmune thyroiditis and 8% of women (10% of women over 55 years of age) and 3% of men have subclinical hypothyroidism. Approximately one third of patients with newly diagnosed overt hypothyroidism have received destructive therapy for hyperthyroidism and indefinite surveillance is required. There is not much that can be done to prevent the occurrence of spontaneous autoimmune hypothyroidism, but if identified early, something can be done to prevent progression to overt disease. Controversy exists as to whether healthy adults would benefit from screening for autoimmune thyroid disease because a significant proportion of subjects tested will have evidence of mild thyroid failure. Case finding in women at menopause or visiting a primary care physician with nonspecific symptoms appears justified.
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PMID:Epidemiology and prevention of clinical and subclinical hypothyroidism. 1248 65

Thyroid hormones are of primary importance for the perinatal development of the central nervous system, and for normal function of the adult brain. These hormones primarily regulate the transcription of specific target genes. They increase the cortical serotonergic neurotransmission, and play an important role in regulating central noradrenergic and GABA function. Thyroid deficiency during the perinatal period results in mental retardation. Hypothyroidism of the adults causes most frequently dementia and depression. Other less common clinical pictures include myxoedema coma, dysfunction of cerebellum and cranial nerves. Hypothyroidism also increases predisposition of stroke. Peripheral diseases frequently include polyneuropathy, carpal tunnel syndrome, myalgic state, and rarely myokymia. Nearly all the hyperthyroid patients show minor psychiatric signs, and infrequently psychosis, dementia, confusion state, depression, apathetic thyrotoxicosis, thyrotoxic crisis, seizures, pyramidal signs, or chorea occur. The peripheral complications may be indicated by chronic thyrotoxic myopathy, infiltrative ophthalmopathy, myasthenia gravis, periodic hypokalemic paralysis and polyneuropathy. Generalized resistance to thyroid hormone was confirmed in a number of patients with attention deficit-hyperactivity disorder. Significantly elevated antithyroid antibody titers characterize Hashimoto's encephalopathy. This condition is a rare, acute - subacute, serious, life threatening, but steroid-responsive, relapsing-remitting, autoimmune disease.
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PMID:[Some neurologic and psychiatric complications in endocrine disorders: the thyroid gland]. 1734 50

We report on 3 kindred patients with terminal 11q monosomy and distal 22q trisomy involving the SHANK3 gene, resulting from a subtle familial translocation t(11;22)(q24.2;q13.33). The patients presented with the characteristic symptoms of Jacobsen syndrome (JBS), including: mental retardation, short stature, and craniofacial dysmorphism in all 3 cases; cardiac defects in 2 cases; and thrombocytopenia, brain abnormality, eye coloboma, recurrent infections, cryptorchidism and toe anomalies in single cases. The oldest patient also had Hashimoto disease and diabetes mellitus type 2. So far, these 2 conditions have not been reported in adult patients with JBS. Features typical for distal 22q trisomy in our patients include muscular hypotonia and prenatal failure to thrive, seen in 2 and 1 cases, respectively. We also present a family member with 11q24.2-qter trisomy and 22q13.33-qter monosomy, whose clinical phenotype is partially overlapping with several dysmorphic features of JBS. In addition, multiple pregnancy losses and infantile deaths occurred in this family, suggesting that these chromosomal imbalances may produce a lethal phenotype. FISH with a panel of BAC probes determined the accurate sizes of the deletion 11q (9.9 Mb) and trisomy 22q (0.8 Mb). To date, only 5 cases of submicroscopic 22q13.3-qter trisomy have been reported. A detailed clinical description of our patients, along with a precise cytogenetic designation of chromosomal breakpoints, allow further refinement of genotype-phenotype correlation for distal imbalances in 11q and 22q.
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PMID:Subtle familial translocation t(11;22)(q24.2;q13.33) resulting in Jacobsen syndrome and distal trisomy 22q13.3: further details of genotype-phenotype maps. 1902 87