To provide further evidence for the role of long-term epigenetic effects of an extra chromosome 21 on HPT-axis associated genes as an explanation of DS associated thyroid phenotype, in a series of DS individuals in whom data on thyroid functioning…
ID
Source
Brief title
Condition
- Chromosomal abnormalities, gene alterations and gene variants
- Thyroid gland disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
DNA methylation differences of HPT-axis associated genes in DS children with
the most severe thyroid phenotype compared to those with the mildest thyroid
phenotype.
Secondary outcome
Thyroid function tests (TSH, free T4, anti-TPO):
Data on thyroid function are available from the neonatal age up to 10 years.
Although we do not expect the severity of the initial thyroid phenotype to have
changed it is important to verify the initial thyroid phenotype with a recent
measurement of thyroid function. It is also important to identify patients who
may have developed autoimmune thyroiditis (anti-TPO positivity) since the age
of 10 years because these patients would have to be excluded.
Background summary
Down syndrome (DS) is characterized by an extra chromosome 21 and is associated
with various congenital malformations. DS is also associated with a specific
thyroid phenotype characterised by mild plasma TSH elevation and slightly lower
T4 concentrations. The reason for this different set of thyroid values in DS is
unknown and whether or not this needs treatment remains a matter of debate.
Previous studies have provided evidence that the extra chromosome 21 in trisomy
21 has epigenetic effects on loci outside this chromosome that are relevant to
DS associated phenotypes. We hypothesize that the Down syndrome associated
thyroid phenotype may be the result of the epigenetic effect of an extra
chromosome 21 on genes associated with the hypothalamic-pituitary-thyroid
(HPT)-axis set point. In a recent (as yet unpublished) study we analysed DNA
methylation patterns of 179 HPT-axis associated genes in 10 neonates with DS
and found 151 genes to be significantly differently methylated compared to 10
controls. Data om thyroid phenotype were not available in this study (protocol
2015_211).
Study objective
To provide further evidence for the role of long-term epigenetic effects of an
extra chromosome 21 on HPT-axis associated genes as an explanation of DS
associated thyroid phenotype, in a series of DS individuals in whom data on
thyroid functioning at birth are available.
Study design
Observational study with invasive measurements
Study burden and risks
The burden is limited to a single visit to the AMC and a single blood sampling
(12 ml). The risks of this study are minimal for the participants and consists
of possible hematoma.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
Between 1999 and 2001, a randomized clinical trial (RCT) was conducted at our centre in a cohort of Down syndrome infants to study the effects of thyroxin treatment versus placebo on psychomotor development. A follow-up study was performed in 2012 (at age 10.7 years). Since this is a cohort of children with Down syndrome that has been extensively phenotypically characterised including data on thyroid function, they provide an excellent opportunity to compare long-term effects.
For the purpose of this study only children from the placebo group will be included, and only in the group not on thyroid hormone treatment and without evidence of thyroid autoimmunity, to avoid influences of treatment and additional morbidity on the methylation pattern. Permission for re-contacting has been obtained in the past.
Exclusion criteria
Children from the treatment group in the original trial. Children currently on thyroid hormone treatment. Children with signs of thyroid autoimmunity.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL55622.018.15 |