Search results for "thyroid dysgenesis"
showing 10 items of 11 documents
Novel Mutations in the NKX2.1 gene and the PAX8 gene in a Boy with Brain-Lung-Thyroid Syndrome
2017
Abstract Objective To elucidate the molecular mechanism which causes thyroid dysgenesis (TD) in a boy with brain-lung-thyroid syndrome. Design, patients, measurements We describe a patient with TD, respiratory disease and cerebral palsy who is heterozygous for mutations in two different genes, the PAX8 (p.E234K) and the NKX2.1 (p.A329GfsX108). In vitro studies were performed to functionally characterize these mutations. Congenital hypothyroidism (CH) was identified by neonatal screening associated with a hypoplastic thyroid gland. Postpartum he developed a brain-lung-thyroid syndrome with severe respiratory failure, symptomatic epilepsy and a considerable psychomotor retardation. The DNA-bi…
Mutations in the NKX2.1 and the PAX8 genes in a boy with thyroid dysgenesis, respiratory and neurological disorders
2015
s of the 51st Workshop for Pediatric Research 51st Workshop for Pediatric Research Gottingen, Germany
Congenital hypothyroidism: A 2020-2021 consensus guidelines update-An ENDO-European Reference Network initiative endorsed by the European Society for…
2021
Background: An ENDO-European Reference Network (ERN) initiative was launched that was endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology with 22 participants from the ENDO-ERN and the two societies. The aim was to update the practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). A systematic literature search was conducted to identify key articles on neonatal screening, diagnosis, and management of primary and central CH. The evidence-based guidelines were graded with the Grading of Recommendations, Assessment, Development and Evaluation system, describing both the strength of recommendations and the quali…
Hepatic incidentaloma: An asymptomatic ectopic thyroid tissue
2022
An ectopic thyroid is a form of thyroid dysgenesis in which the entire thyroid gland or parts of it may be located in another part of the body than the usual place. The most frequent location is the base of the tongue. Although most cases are asymptomatic, symptoms related to tumor size and its relationship with surrounding tissues, hormonal dysfunction, and seldom malignancy may also occur. Here, we describe the case of an asymptomatic woman who was thyroidectomized 19 years previously for a toxic goiter and treated with conventional L-thyroxine therapy, until we enacted a progressive reduction of dosage of the replacement therapy. Incidentally, because of occasional abdomen discomfort, sh…
A New Mutation in the Promoter Region of the PAX8 Gene Causes True Congenital Hypothyroidism with Thyroid Hypoplasia in a Girl with Down's Syndrome
2014
Thyroid dysfunction is common in newborn infants with Down's syndrome (DS), but defects causing classic thyroid dysgenesis (TD) with permanent congenital hypothyroidism (CH) have not been described.We studied a girl with DS and CH who had a mutation in the promoter sequence of the PAX8 gene.A female infant was found to have trisomy 21 and CH, with a venous thyrotropin (TSH) of150 mU/L and a free thyroxine (fT4) of 15.1 pmol/L (day 12). Thyroid peroxidase antibodies and thyroglobulin antibodies were elevated. Scintigraphy showed normal uptake, but ultrasound identified a small gland with heterogenous echotexture and cystic changes. Sequence analysis of the PAX8 gene revealed a new heterozygo…
Two Cases of Thyroid Dysgenesis Caused by Different Novel PAX8 Mutations in the DNA-Binding Region: In Vitro Studies Reveal Different Pathogenic Mech…
2013
Mutations in PAX8, a transcription factor gene, cause thyroid dysgenesis (TD). The extreme variability of the thyroid phenotype makes it difficult to identify individuals harboring PAX8 gene mutations. Here we describe two patients with TD and report two novel PAX8 gene mutations (S54R and R133Q). We performed in vitro studies to functionally characterize these mutations.Using PAX8 expression vectors, we investigated whether the PAX8 mutants localized correctly to the nucleus. To analyze the DNA-binding properties of S54R and R133Q, electrophoretic mobility shift assays were performed. Furthermore, we measured whether the mutant PAX8 proteins were able to activate the thyroglobulin (TG)- an…
Developmental Abnormalities of the Thyroid
2016
Developmental anomalies of the thyroid gland (thyroid dysgenesis) underlie the majority of cases of congenital hypothyroidism. Only a small number of monogenic defects have been shown to result in athyreosis or orthotopic thyroid hyperplasia, whereas the commonest developmental anomaly, thyroid ectopy, remains unexplained. Ectopy may result from multiple genetic or epigenetic hits in the germline and/or at the somatic level. This chapter gives a brief overview of the monogenic defects in candidate genes that have been identified so far and of the syndromes that are known to be associated with thyroid dysgenesis. In addition, we discuss gain-of-function mutations of the thyroid hormone stimu…
Behavioural correlates of early-treated congenital hypothyroidism
2007
Parents' and teachers' ratings were used to evaluate the behavioural characteristics of children with early-treated congenital hypothyroidism (CH). Comparisons were made between 63 children with early-treated CH and 34 healthy controls at the ages of 7.5 and 9.5 y. Additional comparisons were made between the two largest CH subgroups (thyroid agenesis, thyroid dysgenesis) and controls. The most marked differences were found on the introversion cluster and the motor clumsiness scale within it. Children with CH, particularly those with thyroid agenesis, showed introversion and motor clumsiness rather than social negativity and inattention. It is suggested that this behavioural profile may wel…
Developmental Abnormalities of the Thyroid
2010
Publisher Summary This chapter explores the abnormalities in the development of the thyroid gland during organogenesis referred to as thyroid dysgenesis. Permanent primary congenital hypothyroidism (CH) is mentioned to be the most common congenital endocrine disorder as estimated from systematic biochemical screening of newborns. The functional disorders of the thyroid gland are known as thyroid dyshormonogenesis and this disorder is typically inherited in an autosomal recessive manner and common in populations with a high degree of consanguinity. It briefly reviews the single gene disorders that cause CH from thyroid dysgenesis, and mutations that activate the thyrotropin receptor (TSH) re…
Mutations in the NKX2.5 Gene and the PAX8 Promoter in a Girl with Thyroid Dysgenesis
2011
Screening of the known candidate genes involved in thyroid organogenesis has revealed mutations in a small subset of patients with congenital hypothyroidism due to thyroid dysgenesis (TD).We studied a girl with TD who had mutations in two transcription factors involved in thyroid development.Sequencing analysis of candidate genes involved in thyroid gland development revealed a new paternally inherited heterozygous mutation in the NKX2.5 gene (S265R) and a new maternally inherited heterozygous mutation in the PAX8 promoter region (-456CT). Both parents and a brother, who was also heterozygous for both mutations, were phenotypically normal. Immunofluorescence microscopy showed a correct nucl…