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Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital hypothyroidism is a common preventable cause of mental retardation. The overall incidence is approximately 1:4000; females are affected about twice as often as males. Approximately 85% of cases are sporadic, while 15% are hereditary. The most common sporadic etiology is thyroid dysgenesis, with ectopic glands more common than aplasia or hypoplasia. While the pathogenesis of dysgenesis is largely unknown, some cases are now discovered to be the result of mutations in the transcription factors PAX-8 and TTF-2. Loss of function mutations in the thyrotropin (TSH) receptor have been demonstrated to cause some familial forms of athyreosis. The most common hereditary etiology is the inborn errors of thyroxine (T4) synthesis. Recent mutations have been described in the genes coding for the sodium/iodide symporter, thyroid peroxidase (TPO), and thyroglobulin. Transplacental passage of a maternal thyrotropin receptor blocking antibody (TRB-Ab) causes a transient form of familial congenital hypothyroidism. The vast majority of infants are now diagnosed after detection through newborn screening programs using a primary T4-backup TSH or primary TSH test. Screening test results must be confirmed by serum thyroid function tests. Thyroid scintigraphy, using 99mTc or 123I, is the most accurate diagnostic test to detect thyroid dysgenesis or one of the inborn errors of T4 synthesis. Thyroid sonography is nearly as accurate, but it may miss some cases of ectopic glands. If maternal antibody-mediated hypothyroidism is suspected, measurement of maternal and/or neonatal TRB-Ab will confirm the diagnosis. The goals of treatment are to raise the serum T4 as rapidly as possible into the normal range, adjust the levothyroxine dose with growth to keep the serum T4 (or free T4) in the upper half of the normal range and the TSH normal, and maintain normal growth and development while avoiding overtreatment. An initial starting dose of 10-15 microg/kg per day is recommended; this dose will decrease on a weight basis over time. Serum T4 (or free T4) and TSH should be monitored every 1-2 months in the first year of life and every 2-3 months in the second and third years.
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PMID:Congenital hypothyroidism: etiologies, diagnosis, and management. 1044 22

Congenital hypothyroidism is the most common congenital endocrine disorder (one newborn in 3000) and represents the most common cause of preventable mental retardation. In 10-20% of cases, it is due to autosomal recessive functional disorders leading to goiter formation (thyroid dyshormonogenesis). In the remainder, it is due to thyroid dysgenesis, which comprises usually isolated defects in: (1) migration of the median thyroid anlage, leading to a round cluster of ectopic cells (usually in a sublingual position) with no other thyroid tissue present; (2) differentiation or survival of the thyroid follicular cells leading to athyreosis; and (3) growth of a thyroid with the normal bilobed shape and in the normal cervical position (orthotopic hypoplasia). Mouse knock-outs have demonstrated that thyroid transcription factor-1 (TTF-1) and PAX8 are required for the survival and proliferation of thyroid follicular cell precursors, TTF-2 for their downward migration and the thyrotropin receptor (TSHR) for post-natal thyroid growth. In humans, thyroid dysgenesis is generally a sporadic malformation but an affected relative is found in 2% of cases, a figure 15-fold higher than by chance alone. Pedigree analysis is most compatible with dominant inheritance with variable penetrance. However, mutations in TTF-1, TTF-2, PAX8 and TSHR are found in <10% of patients with congenital hypothyroidism and these predominantly have orthotopic thyroid hypoplasia, often associated with other malformations. This low yield and the discordance of >90% of monozygotic twin pairs suggests that isolated thyroid ectopy or athyreosis most often results from early somatic mutations, epigenetic modifications or stochastic developmental events.
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PMID:Development of the thyroid gland: lessons from congenitally hypothyroid mice and men. 1278 49

Congenital hypothyroidism is the principle cause of preventable mental retardation, with a prevalence of 1 in 3,500 neonates. The disorder may be permanent or transitory. Permanent congenital hypothyroidism is caused principally by thyroid dysgenesis. In industrialized countries, mass screening allows the disorder to be diagnosed at birth. The severity is variable but is generally more pronounced in females. The majority of studies point to a genetic origin for the disease and no consistent evidence has been found to suggest a major role for environmental factors. The genetic factors have already been identified and involve several elements (mutations in the TTF-1, TTF-2, PAX8 and TSH receptor genes). The etiological diagnosis is based on scintigraphy, ultrasound and the level of circulating thyroglobulin. At present, treatment is administered at an adapted dose during the first two weeks of life and should allow the child to reach its full intellectual potential. However, minor anomalies have been reported in some treated children, suggesting that this treatment cannot compensate for a certain degree of foetal hypothyroidism.
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PMID:[Congenital hypothyroidism]. 1707 33

Wilm's tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome, a rare genetic disorder, is caused by the loss of 11p13 region including PAX6 and WT1. We report novel findings in a 28-month-old boy with aniridia, Wilm's tumor, congenital hypothyroidism, and sublingual thyroid ectopia. He was found to have a mosaic 5.28 Mb interstitial deletion of chromosome 11p13 deleting PAX6 and WT1. In order to clarify the mechanism underlying his thyroid dysgenesis, sequence analysis of candidate thyroid developmental genes was performed. We identified a FOXE1: c.532_537delGCCGCC p.(Ala178_Ala179del) variant that predisposes to thyroid ectopia. Taken together, this is the first report of mosaic 11p13 deletion in association with thyroid dysgenesis. We also propose a model of complex interactions of different genetic variants for this particular phenotype in the present patient.
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PMID:WAGR syndrome and congenital hypothyroidism in a child with a Mosaic 11p13 deletion. 2839 7

Congenital hypothyroidism has an incidence of 1:3000-4000 newborns. In the past, it was a common cause of mental retardation, although newborn screening has improved the prognosis. Several transcription factors are crucial to the early organogenesis of the thyroid, including TITF1, FOXE1, PAX8 and HHEX. Nevertheless, a small minority of humans with congenital hypothyroidism carry mutations in these genes. Long-term follow-up studies show that with appropriate therapy, the mental and physical development of congenital hypothyroidism patients is in the normal range, although somewhat delayed when compared with appropriate controls. Critical issues of treatment include early diagnosis and rapid correction of hypothyroidism by ensuring rapid initiation of treatment and rapid normalization of thyroid-stimulating hormone levels, especially in cases of severe congenital hypothyroidism. There has been recent question of the need to treat premature infants with hypothyroxinemia but no elevation of the thyroid-stimulating hormone concentration. Numerous controlled studies of the short- and long-term effects of thyroid hormone supplementation have not shown a consistent benefit in this group of patients. Future research will investigate further the genetic underpinnings of the condition. There is a worldwide need to prevent congenital hypothyroidism by ensuring adequate dietary iodine and to develop infrastructure to diagnose and treat congenital hypothyroidism in developing countries.
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PMID:Genetics, clinical management and natural history of congenital hypothyroidism. 3075 39