Unravelling the aetiology of pyloric stenosis; a role for the COL3A1 gene?

Pyloric stenosis is a relatively common gastro-enterologic condition in
newborns. A surgical approach, by means of a pylorotomy, is the general
treatment of this disorder.
The aetiology of pyloric stenosis is largely unknown.
There are several studies suggesting a genetic basis for pyloric stenosis.
Reports of multiple affected individuals in one family have been published.
Furthermore, coexistence with congenital malformations and syndromes point to a
genetic involvement as well. Up till now, no locus in the human genome has been
found to be evidently associated with pyloric stenosis.
It is remarkable that pyloric stenosis is also seen in patients with Ehlers
Danlos type IV, an inherited connective tissue disorder, caused by mutations of
the COL3A1 gene and that next to this a group of patients with pyloric stenosis
is reported with evidently more frequent occurrence of hypermobility of the
joints (one of the symptoms of Ehlers Danlos Syndrome) than is seen in the
healthy population.

The aim of this study is to improve insight in potentially genetic factors
contributing to the development of pyloric stenosis.
We aim to investigate the association of the COL3A1 gene and pyloric stenosis
because of concrete signs in the existing literature for an association.

In a cross-sectional cohort study, we will include consequent newborns
diagnosed with pyloric stenosis and therefore undergoing a pylorotomy.
After informed consent is obtained, 0.5 ml of EDTA blood from an existing
intravenous canules and a biopsie of connective tissue from the main incision
will be taken from the patient.
Parents are asked to fill out a questionnaire concerning the medical history of
the child and to answer questions about occurrence of gastrointestinal motility
disorders and connective tissue disorders in their families.
Blood and tissue will be analyzed in the DNA and protein laboratory of the VU
Medical Centre in Amsterdam. Polymorphisms or mutations will be compared to the
normal results of a healthy population, available in the database of the
laboratory.

At first, we will include 5 patients and make a subanalysis. Whenever we find
mutations or polymorphisms in this group, we will proceed to include more
patients, with a maximum of 25 to 30.
Given the explorative character of this study, it is impossible the make an
exact power calculation preceding the study.

It will take parents about 20 minutes to complete the questionnaire.
Patients will be under complete anesthesia during the pylorotomy. During the
procedure, blood from an existing intravenous canule will be taken and a
biopsie will be performed.
The extra biopsy taken during the surgical procedure does not involve an
increased risk for the patient.