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Article ; Online: Genetics of congenital hypothyroidism: Modern concepts.

Stoupa, Athanasia / Kariyawasam, Dulanjalee / Polak, Michel / Carré, Aurore

Pediatric investigation

2022 Volume 6, Issue 2, Page(s) 123–134

Abstract: Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and one of the most common preventable causes of intellectual disability in the world. CH may be due to developmental or functional thyroid defects (primary or peripheral CH) ... ...

Abstract	Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and one of the most common preventable causes of intellectual disability in the world. CH may be due to developmental or functional thyroid defects (primary or peripheral CH) or be hypothalamic-pituitary in origin (central CH). In most cases, primary CH is caused by a developmental malformation of the gland (thyroid dysgenesis, TD) or by a defect in thyroid hormones synthesis (dyshormonogenesis, DH). TD represents about 65% of CH and a genetic cause is currently identified in fewer than 5% of patients. The remaining 35% are cases of DH and are explained with certainty at the molecular level in more than 50% of cases. The etiology of CH is mostly unknown and may include contributions from individual and environmental factors. In recent years, the detailed phenotypic description of patients, high-throughput sequencing technologies, and the use of animal models have made it possible to discover new genes involved in the development or function of the thyroid gland. This paper reviews all the genetic causes of CH. The modes by which CH is transmitted will also be discussed, including a new oligogenic model. CH is no longer simply a dominant disease for cases of CH due to TD and recessive for cases of CH due to DH, but a far more complex disorder.
Language	English
Publishing date	2022-05-14
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2574-2272
ISSN (online)	2574-2272
DOI	10.1002/ped4.12324
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Article ; Online: Génétique de l’hypothyroïdie congénitale.

Stoupa, Athanasia / Kariyawasam, Dulanjalee / Polak, Michel / Carré, Aurore

Medecine sciences : M/S

2022 Volume 38, Issue 3, Page(s) 263–273

Abstract: Congenital hypothyroidism (CH) is the most frequent neonatal endocrine disorder. CH is due to thyroid development or thyroid function defects (primary) or may be of hypothalamic-pituitary origin (central). Primary CH is caused essentially by abnormal ... ...

Title translation	Genetic of congenital hypothyroidism.
Abstract	Congenital hypothyroidism (CH) is the most frequent neonatal endocrine disorder. CH is due to thyroid development or thyroid function defects (primary) or may be of hypothalamic-pituitary origin (central). Primary CH is caused essentially by abnormal thyroid gland morphogenesis (thyroid dysgenesis, TD) or defective thyroid hormone synthesis (dyshormonogenesis, DH). DH accounts for about 35% of CH and a genetic cause is identified in 50% of patients. However, TD accounts for about 65% of CH, and a genetic cause is identified in less than 5% of patients. The pathogenesis of CH is largely unknown and may include the contribution of individual and environmental factors. During the last years, detailed phenotypic description of patients, next-generation sequence technologies and use of animal models allowed the discovery of novel candidate genes in thyroid development and function. We provide an overview of recent genetic causes of primary and central CH. In addition, mode of inheritance and the oligogenic model of CH are discussed.
MeSH term(s)	Congenital Hypothyroidism/genetics ; Databases, Genetic ; Humans ; Mutation ; Thyroid Dysgenesis/genetics ; Thyroid Hormones
Chemical Substances	Thyroid Hormones
Language	French
Publishing date	2022-03-25
Publishing country	France
Document type	Journal Article
ZDB-ID	632733-3
ISSN	1958-5381 ; 0767-0974
ISSN (online)	1958-5381
ISSN	0767-0974
DOI	10.1051/medsci/2022028
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Article ; Online: Approach to the Patient With Congenital Hypothyroidism.

Stoupa, Athanasia / Kariyawasam, Dulanjalee / Nguyen Quoc, Adrien / Polak, Michel / Carré, Aurore

The Journal of clinical endocrinology and metabolism

2022 Volume 107, Issue 12, Page(s) 3418–3427

Abstract: Congenital hypothyroidism (CH) is the most frequent neonatal endocrine disorder and the most common preventable cause of development delay and growth failure if diagnosed and treated early. The thyroid is the first endocrine gland to develop during ... ...

Abstract	Congenital hypothyroidism (CH) is the most frequent neonatal endocrine disorder and the most common preventable cause of development delay and growth failure if diagnosed and treated early. The thyroid is the first endocrine gland to develop during embryonic life and to be recognizable in humans. Thyroid development and maturation can be divided into 2 phases: a first phase of embryogenesis and a second phase of folliculogenesis and differentiation with thyroid hormone production at the final steps. Regulation of the thyroid function requires normal development of the hypothalamic-pituitary-thyroid axis, which occurs during the embryonic and neonatal period. Defects in any of steps of thyroid development, differentiation, and regulation lead to permanent CH. Newborn screening programs, established in only one-third of countries worldwide, detect CH and are cost-effective and highly sensitive and specific. During the last decade, epidemiology of CH has changed with increased frequency of thyroid in situ in primary CH. Advances in molecular testing have expanded knowledge and understanding of thyroid development and function. However, a molecular cause is identified in only 5% of CH due to thyroid dysgenesis. The purpose of this article is to describe the clinical approach to the child with CH, focusing on diagnostic work-up and future challenges on optimizing thyroid replacement therapy and regenerative medicine. The review is written from the perspective of the case of 2 girls referred for CH after newborn screening and diagnosed with thyroid ectopy. The genetic work-up revealed novel mutations in TUBB1 gene, associated with large platelets and abnormal platelet physiology.
MeSH term(s)	Child ; Female ; Humans ; Infant, Newborn ; Congenital Hypothyroidism/diagnosis ; Congenital Hypothyroidism/genetics ; Congenital Hypothyroidism/therapy ; Neonatal Screening ; Thyroid Dysgenesis/complications ; Thyroid Hormones
Chemical Substances	Thyroid Hormones
Language	English
Publishing date	2022-09-15
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgac534
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Article ; Online: Resolved Severe Primary Hypothyroidism in Sensenbrenner Syndrome Post Hepatorenal Transplantation: A Case Report.

Al Noaim, Khalid / Alfadhel, Majid / Carré, Aurore / Polak, Michel / Al Mutair, Angham

Hormone research in paediatrics

2022 Volume 96, Issue 4, Page(s) 426–431

Abstract: Introduction: Sensenbrenner syndrome, or cranioectodermal dysplasia (OMIM #218330), is a rare genetic condition inherited as an autosomal recessive with less than 70 reported cases worldwide. It results in multiorgan abnormalities along with ectodermal ... ...

Abstract	Introduction: Sensenbrenner syndrome, or cranioectodermal dysplasia (OMIM #218330), is a rare genetic condition inherited as an autosomal recessive with less than 70 reported cases worldwide. It results in multiorgan abnormalities along with ectodermal structural defects. No previous reported cases demonstrated primary hypothyroidism in a matter of Sensenbrenner syndrome. Case presentation: Herein, we report a 6-year-old girl who suffered from progressive liver failure and end-stage renal disease secondary to Sensenbrenner syndrome, which was associated with severe primary hypothyroidism that completely recovered after a combined renal and liver transplant. Conclusion: For the first time in the literature, we report an association of Sensenbrenner syndrome with hypothyroidism that resolved after a combined renal and liver transplant. Such findings expand the clinical spectrum of this syndrome. However, a larger cohort is needed to confirm or exclude such an association. Our case highlights the importance of thyroid function monitoring in any patient with renal and liver failure prior to and after a hepatorenal transplant.
MeSH term(s)	Female ; Humans ; Child ; Ectodermal Dysplasia/complications ; Ectodermal Dysplasia/genetics ; Craniosynostoses/complications ; Craniosynostoses/genetics ; Bone and Bones ; Liver Failure/complications
Language	English
Publishing date	2022-12-13
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2537278-6
ISSN	1663-2826 ; 1663-2818
ISSN (online)	1663-2826
ISSN	1663-2818
DOI	10.1159/000528660
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Article ; Online: Ex vivo model for elucidating the functional and structural differentiation of the embryonic mouse thyroid.

Carré, Aurore / Gawade, Sanjay / Dertschnig, Simone / Hafen, Kathrin / Polak, Michel / Szinnai, Gabor

Molecular and cellular endocrinology

2020 Volume 510, Page(s) 110834

Abstract: Terminal thyroid gland differentiation - the last developmental step needed to enable thyroid hormone (T4) synthesis - involves profound structural and biochemical changes in the thyroid follicular cells (TFCs). We aimed to develop an ex vivo thyroid ... ...

Abstract	Terminal thyroid gland differentiation - the last developmental step needed to enable thyroid hormone (T4) synthesis - involves profound structural and biochemical changes in the thyroid follicular cells (TFCs). We aimed to develop an ex vivo thyroid model of embryonic mouse thyroid that would replicate the in vivo TFC differentiation program. E13.5 thyroid explants were cultured ex vivo in chemically defined medium for 7 days. Immunostaining and qPCR of thyroid explants showed thyroglobulin production onset, follicle formation, and T4 synthesis onset in 1-, 3-, and 5-day-old cultures, respectively. Differentiation was maintained and follicular growth continued throughout the 7-day culture period. Pharmacological approaches to culture inhibition were performed successfully in the ex vivo thyroids. Our robust and well described ex vivo thyroid culture model replicates the sequence of thyroid differentiation to T4 synthesis seen in vivo. This model can be used to test the effects of pharmacological inhibitors on thyroid hormone production.
MeSH term(s)	Animals ; Cell Differentiation ; Embryo, Mammalian/anatomy & histology ; Embryonic Development/genetics ; Gene Expression Regulation, Developmental ; Mice ; Microdissection ; Models, Biological ; Receptors, Notch/metabolism ; Thyroglobulin/metabolism ; Thyroid Gland/anatomy & histology ; Thyroid Gland/embryology ; Thyroid Gland/physiology ; Tissue Survival/physiology
Chemical Substances	Receptors, Notch ; Thyroglobulin (9010-34-8)
Language	English
Publishing date	2020-04-28
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	187438-x
ISSN	1872-8057 ; 0303-7207
ISSN (online)	1872-8057
ISSN	0303-7207
DOI	10.1016/j.mce.2020.110834
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Article: Borealin/CDCA8 deficiency alters thyroid development and results in papillary tumor-like structures.

Didier-Mathon, Hortense / Stoupa, Athanasia / Kariyawasam, Dulanjalee / Yde, Sonny / Cochant-Priollet, Beatrix / Groussin, Lionel / Sébag, Frédéric / Cagnard, Nicolas / Nitschke, Patrick / Luton, Dominique / Polak, Michel / Carré, Aurore

Frontiers in endocrinology

2023 Volume 14, Page(s) 1286747

Abstract: Background: BOREALIN: Methods: We characterized thyroid development and function in Borealin-deficient (: Results: Thyroid development was impaired with a hyperplastic anlage on embryonic day E9.5 followed by thyroid hypoplasia from E11.5 onward. ... ...

Abstract	Background: BOREALIN Methods: We characterized thyroid development and function in Borealin-deficient ( Results: Thyroid development was impaired with a hyperplastic anlage on embryonic day E9.5 followed by thyroid hypoplasia from E11.5 onward. Adult Conclusion: These findings demonstrate Borealin involvement in critical steps of thyroid structural development and function throughout life. They support a role for Borealin in thyroid dysgenesis with congenital hypothyroidism. Close monitoring for thyroid cancer seems warranted in patients carrying
MeSH term(s)	Animals ; Mice ; Cell Cycle Proteins/genetics ; Congenital Hypothyroidism/genetics ; Thyroid Cancer, Papillary/genetics ; Thyroid Dysgenesis/genetics ; Thyroid Neoplasms/genetics
Chemical Substances	CDCA8 protein, human ; Cell Cycle Proteins ; CDCA8 protein, mouse
Language	English
Publishing date	2023-10-27
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2023.1286747
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Article ; Online: New genetics in congenital hypothyroidism.

Stoupa, Athanasia / Kariyawasam, Dulanjalee / Muzza, Marina / de Filippis, Tiziana / Fugazzola, Laura / Polak, Michel / Persani, Luca / Carré, Aurore

Endocrine

2021 Volume 71, Issue 3, Page(s) 696–705

Abstract: Introduction: Congenital hypothyroidism (CH) is the most frequent neonatal endocrine disorder and one of the most common preventable forms of mental retardation worldwide. CH is due to thyroid development or thyroid function defects (primary) or may be ... ...

Abstract	Introduction: Congenital hypothyroidism (CH) is the most frequent neonatal endocrine disorder and one of the most common preventable forms of mental retardation worldwide. CH is due to thyroid development or thyroid function defects (primary) or may be of hypothalamic-pituitary origin (central). Primary CH is caused essentially by abnormal thyroid gland morphogenesis (thyroid dysgenesis, TD) or defective thyroid hormone synthesis (dyshormonogenesis, DH). TD accounts for about 65% of CH, however a genetic cause is identified in less than 5% of patients. Purpose: The pathogenesis of CH is largely unknown and may include the contribution of individual and environmental factors. During the last years, detailed phenotypic description of patients, next-generation sequence technologies and use of animal models allowed the discovery of novel candidate genes in thyroid development, function and pathways. Results and conclusion: We provide an overview of recent genetic causes of primary and central CH. In addition, mode of inheritance and the oligogenic model of CH are discussed.
MeSH term(s)	Congenital Hypothyroidism/genetics ; Databases, Genetic ; Humans ; Infant, Newborn ; Mutation ; Thyroid Dysgenesis/genetics ; Thyroid Hormones
Chemical Substances	Thyroid Hormones
Language	English
Publishing date	2021-03-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1194484-5
ISSN	1559-0100 ; 1355-008X ; 0969-711X
ISSN (online)	1559-0100
ISSN	1355-008X ; 0969-711X
DOI	10.1007/s12020-021-02646-9
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Article ; Online: Update of Thyroid Developmental Genes.

Stoupa, Athanasia / Kariyawasam, Dulanjalee / Carré, Aurore / Polak, Michel

Endocrinology and metabolism clinics of North America

2016 Volume 45, Issue 2, Page(s) 243–254

Abstract: Thyroid dysgenesis (TD) is the most common cause of congenital hypothyroidism in iodine-sufficient regions and includes a spectrum of developmental anomalies. The genetic components of TD are complex. Although a sporadic disease, advances in ... ...

Abstract	Thyroid dysgenesis (TD) is the most common cause of congenital hypothyroidism in iodine-sufficient regions and includes a spectrum of developmental anomalies. The genetic components of TD are complex. Although a sporadic disease, advances in developmental biology have revealed monogenetic forms of TD. Inheritance is not based on a simple Mendelian pattern and additional genetic elements might contribute to the phenotypic spectrum. This article summarizes the key steps of normal thyroid development and provides an update on responsible genes and underlying mechanisms of TD. Up-to-date technologies in genetics and biology will allow us to advance in our knowledge of TD.
Language	English
Publishing date	2016-06
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	92116-6
ISSN	1558-4410 ; 0889-8529
ISSN (online)	1558-4410
ISSN	0889-8529
DOI	10.1016/j.ecl.2016.01.007
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Article ; Online: Down syndrome and nonautoimmune hypothyroidisms in neonates and infants.

Kariyawasam, Dulanjalee / Carré, Aurore / Luton, Dominique / Polak, Michel

Hormone research in paediatrics

2015 Volume 83, Issue 2, Page(s) 126–131

Abstract: Down syndrome is characterized by a high prevalence of thyroid dysfunction during childhood. In this paper, we review the different kinds of thyroid dysfunction that occur excluding those of autoimmune origin: congenital hypothyroidism (elevated plasma ... ...

Abstract	Down syndrome is characterized by a high prevalence of thyroid dysfunction during childhood. In this paper, we review the different kinds of thyroid dysfunction that occur excluding those of autoimmune origin: congenital hypothyroidism (elevated plasma TSH with low plasma T4 occurring at birth usually detected by neonatal screening), subclinical hypothyroidism (elevated plasma TSH with plasma T4 in the normal range, which can be congenital or acquired) and acquired primary hypothyroidism (elevated plasma TSH and low plasma T4 occurring after birth). These dysfunctions, while not due to autoimmunity, are of thyroidal origin. However, the mechanisms leading to these different thyroidal abnormalities have not been clearly defined; in particular, it is difficult to determine whether the different types of dysfunction have a common cause, or if the causes are distinct. Treatment is prescribed according to the type of thyroidal abnormality.
MeSH term(s)	Congenital Hypothyroidism/blood ; Congenital Hypothyroidism/complications ; Congenital Hypothyroidism/pathology ; Congenital Hypothyroidism/therapy ; Down Syndrome/blood ; Down Syndrome/complications ; Down Syndrome/pathology ; Down Syndrome/therapy ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Prevalence ; Thyroid Gland/abnormalities ; Thyroid Gland/metabolism ; Thyrotropin/blood ; Thyroxine/blood
Chemical Substances	Thyrotropin (9002-71-5) ; Thyroxine (Q51BO43MG4)
Language	English
Publishing date	2015
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2537278-6
ISSN	1663-2826 ; 1663-2818
ISSN (online)	1663-2826
ISSN	1663-2818
DOI	10.1159/000370004
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Article ; Online: Non-Intrusive Battery Health Monitoring

Gajewski Laurent / Cenac-Morthe Celine / Carre Aurore / Simon Patrice / Taberna Pierre-Louis

E3S Web of Conferences, Vol 16, p

2017 Volume 07006

Abstract: The “Non-intrusive battery health monitoring”, developed by Airbus Defence and Space (ADS) in cooperation with the CIRIMAT-CNRS laboratory and supported by CNES, aims at providing a diagnosis of the battery ageing in flight, called State of Health (SOH), ...

Abstract	The “Non-intrusive battery health monitoring”, developed by Airbus Defence and Space (ADS) in cooperation with the CIRIMAT-CNRS laboratory and supported by CNES, aims at providing a diagnosis of the battery ageing in flight, called State of Health (SOH), using only the post-treatment of the battery telemetries. The battery current and voltage telemetries are used by a signal processing tool on ground to characterize and to model the battery at low frequencies which allows monitoring the evolution of its degradation with great accuracy. The frequential behaviour estimation is based on inherent disturbances on the current during the nominal functioning of the battery. For instance, on-board thermal control or equipment consumption generates random disturbances on battery current around an average current. The battery voltage response to these current random disturbances enables to model the low frequency impedance of the battery by a signal processing tool. The re-created impedance is then compared with the evolution model of the low frequencies impedance as a function of the battery ageing to estimate accurately battery degradation. Hence, this method could be applied to satellites which are already in orbit and whose battery telemetries acquisition system fulfils the constraints determined in the study. This innovative method is an improvement of present state-of-the-art and is important to have a more accurate in-flight knowledge of battery ageing which is crucial for mission and operation planning and also for possible satellite mission extension or deorbitation. This method is patented by Airbus Defence and Space and CNES.
Keywords	Environmental sciences ; GE1-350
Subject code	150
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	EDP Sciences
Document type	Article ; Online
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