The aim of the present study is to identify genes associated with functional constipation in a homogeneous subgroup of children responding to sacral neuromodulation by performing whole exome sequencing in both children and their parents and to…
ID
Source
Brief title
Condition
- Gastrointestinal tract disorders congenital
- Gastrointestinal motility and defaecation conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is the identification of genes associated with childhood
refractory constipation.
Secondary outcome
The secondary outcome will consist of a thorough description of the clinical
characteristics, the phenotype, of children with refractory constipation
responding to sacral neuromodulation therapy.
Background summary
In children, the reported prevalence of functional constipation varies between
0.7% to 29.6%. Genetic factors are very likely to play an important role in the
pathophysiology of childhood constipation. However, linkage studies,
association studies and direct gene sequencing have failed to identify
mutations in specific genes associated with constipation. This is likely due to
the large heterogeneity of functional constipation in children.
Study objective
The aim of the present study is to identify genes associated with functional
constipation in a homogeneous subgroup of children responding to sacral
neuromodulation by performing whole exome sequencing in both children and their
parents and to subsequently confirm this in a larger group of patients by
molecular analyses. The second aim is to provide a detailed description of the
clinical characteristics of children with refractory constipation.
Study design
Total exome sequencing will be performed in at least 4 children with refractory
constipation responding to sacral neuromodulation therapy and their parents.
Total exome sequencing will be followed by Sanger sequencing of suggestive
genes. Sanger sequencing will also be performed in other participants in order
to confirm the findings. Clinical information will be obtained by a
questionnaire and from files.
Study burden and risks
All participants will be requested to donate 10 mL of peripheral blood for DNA
extraction. If blood donation can be combined with a regular laboratory
assessment, participants will be requested to donate additonally 5 mL of
peripheral blood. Clinical information of participating children is will be
collected from their files and physicians after consent of the participant and
his/her parents . All participating parents of affected children will be asked
to fill out a questionnaire with specific questions about symptoms of
defecation disorders and their health in general.
The risks and burden of venous blood drawing are minimal for both children and
adults.
Meibergdreef 9
Amsterdam
NL
Meibergdreef 9
Amsterdam
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria for the indexpatients:
- Patients diagnosed with functional constipation not responding to maximal conservative treatment (laxatives, enemas, bowel cleansing) for at least 6 months prior to sacral neuromodulation (SNM) therapy, but responding to SNM therapy.
-Patients aged 12-18 years at time of the implantation of the sacral neuromodulator.;Inclusion Criteria for parents of indexpatients:
-Fathers and mothers of indexpatients.;Informed consent is needed for all individuals to be included. Informed consent will also be asked for by the parents as participating children will be aged 12 to 18 years.
Exclusion criteria
Exclusion criteria for the indexpatients
- Patients suffering from organic pathology causing constipation.
-Patients with a history of large bowel surgery, congenital anorectal malformations or neurological disease.
-Patients not able to read and understand the written information. ;Exclusion criteria for the parents of indexpatients
-Individuals not able to read and understand the written information.
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 | NL37602.018.11 |