Clinical Trial: Clinical and Genetic Analysis in Congenital Hypothyroidism Due to Thyroid Dysgenesis.

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Phenotype and Genotype Analysis in Congenital Hypothyroidism Due to Thyroid Dysgenesis. The Use of Genetic Analysis in the Early Care of Children With Thyroid Dysgenesis

Brief Summary:

Congenital hypothyroidism (CH) is a rare disease that affects 1 in 3500 newborn. This condition is detected consistently since the late 1970s in France, which has led to early care and a significant improvement in prognosis and intellectual stature of these children. However neurodevelopmental disorders persist in 10-15% of cases. More associated diseases have been reported in approximately 10% of cases. These observations are in most cases poorly understood. The family nature of the CH is now well recognized and a dozen genes involved up to now. However, in the majority of cases (HC not due to a disorder of the organification of iodine), few mutations have been found in the reported number of patients (5-10%), suggesting the involvement of other genes. Some of the genes have been implicated in particular specific syndromic forms but many pathological associations remain unexplained. Also, a more complete genetic elucidation of CH would enable a better understanding of its etiology and thus its risk of familial recurrence (frequently asked questions by parents of children with CH) and secondly the presence of associated pathologies.

Main goal: to describe the population with CH (not due to a disorder of the organification of iodine) not only on clinical, biological and radiological (phenotypic analysis) but also on the genetic level to establish a genotype / phenotype correlation.


Detailed Summary:

Congenital hypothyroidism (CH) is a rare disease that affects 1 in 3500 newborn. This condition is detected consistently since the late 1970s in France, which has enabled early care and a significant improvement of the intellectual stature and prognosis of these children. However neurodevelopmental disorders persist in 10-15% of cases. More associated pathologies have been reported in nearly 10% of cases. These observations are in most cases poorly understood. The family nature of the HC is now well accepted and a dozen genes is now involved. However in the majority of cases (HC not due to a disorder of the organification of iodine), few mutations have been found relative to the number of patients (5-10%), suggesting the involvement of other genes. Some of the genes have been implicated in such specific syndromic forms but many pathological associations remain unexplained. Also, a more complete elucidation of genetic HC enable a better understanding of its etiology and thus share the risk of familial recurrence (frequently asked by parents of children with questions) and secondly the presence of comorbidities.

Main objective: To describe the population with HC (not due to a disorder of the organification of iodine) not only on clinical, biological and radiological (phenotypic analysis) but also at the genetic level to establish a genotype / phenotype correlation.

Secondary objectives:

  1. study the frequency of malformations and / or pathological associations in patients with HC
  2. identify groups of patients with syndromic forms in whom early treatment may improve the prognosis of children
  3. to search for mutations in genes known to be involved in the pathology
  5. etiological type of the congenital hypothyroidism [ Time Frame: 2 years ]
    Etiological Type of the congenital hypothyroidism: athyreosis, ectopia, hémiagenesis, hypoplastic gland in place of normal shape and size
  6. Presence and type of cytogenetic and / or genetic abnormality associated with HC [ Time Frame: 2 years ]
  7. Presence and type of pathology associated with HC [ Time Frame: 2 years ]
  8. Presence of abnormal neuropsychological (including delayed psychomotor development) [ Time Frame: 2 years ]


    9. Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • time to treatment of hypothyroidism [ Time Frame: 2 years ]
      Optimization of the treatment of hypothyroidism: normalization period of TSH and T4, TSH number of> 15 mU / ml during follow-up, adherence
    • Presence of a prenatal and / or neonatal complication [ Time Frame: 2 years ]


    Original Secondary Outcome: Same as current

    Information By: Assistance Publique - Hôpitaux de Paris

    Dates:
    Date Received: August 2, 2013
    Date Started: May 2013
    Date Completion: September 2017
    Last Updated: August 25, 2016
    Last Verified: August 2016