Long term functional outcome, quality of life, and genetic factors in patients with a cloacal malformation

A cloacal malformation is a severe congenital abnormality. In this rare
condition urethra, vagina and rectum are fused in one common channel,
presenting as one single perineal orifice. With a prevalence of one in 50.000
newborns it accounts for approximately 10% of all anorectal malformations.
Complex surgical repair is needed in order to construct a close to normal
rectourogenital tract. Aim to this surgical approach is achieving appropriate
colorectal, urological and gynecological function. Studies on this long term
functional outcome of patients born with a cloacal malformation are scarce, but
when available, show many cases of impaired colorectal, urological or
gynecological function. These studies are all retrospective and with different
descriptions and scoring systems for functional outcome. A cross-sectional
assessment of functional outcome in patients with a cloacal malformation has
never been conducted. Quality of life studies have been done in patients with
other anorectal malformations (ARM) in the Netherlands and show lower scores in
the ARM group compared to a control group. Quality of life of patients born
with a cloacal malformation has never been assessed. Few studies report bladder
function that is assessed by urological tests. Assessing long-term functional
outcome and the quality of life in patients with a cloacal malformation can
show effectiveness of the current postoperative management in these patients.
Results might indicate a need for adjusted follow-up of patients with a cloacal
malformation in order to achieve higher quality of life.
Further, some studies have been carried out in order to find the genetic origin
of anorectal malformations and cloacal malformations in special. Till so far,
this has not lead to a specific gene or mutation that leads to this congenital
abnormality. Since these patients are born of healthy parents in most cases the
onset of the cloacal malformation seems sporadic. Therefore de novo mutations
might play an important role in the onset of cloacal malformations. Exome
sequencing is a useful technique for identifying de novo mutations, by studying
both parents and affected patient. Information about the genetic onset of
cloacal malformations will increase knowledge about the development of such a
malformation as well as the chances of inheritability of this complex form of
ARM.

The primary objective to our study is assessing functional outcome, quality of
life, and genetic mutations in patients with a cloacal malformation.
Functional outcome:
- Colorectal function
o Objective: assessing colorectal function through the use of a questionnaire
o Question: Do patients with a cloacal malformation have an impaired colorectal
function?

- Urological function
o Objective: assessing urological function through the use of a questionnaire,
ultrasounds of the urinary tract (pre- and postvoiding), and urine samples.
o Question: Do patients with a cloacal malformation have an impaired urological
function?

- Gynecological and sexual function
o Objective: assessing gynecological and sexual function through the use of a
questionnaire.
o Question: Do patients with a cloacal malformation have an impaired
gynecological and sexual function? Do patients with a cloacal malformation have
a normal fertility?

- Renal function
o Objective: assessing renal function through creatinine clearance rates in
blood samples.
o Question: Do patients with a cloacal malformation suffer from renal
dysfunction?

Quality of life:
o Objective: assessing quality of life through conducting two questionnaires
o Question: Do patients with a cloacal malformation have a lower quality of
life?

Genetic mutations:
o Objective: assessing mutations in both study subjects* and parents of study
subjects* DNA by conducting exome sequencing and comparing study subjects*
exome with the exome of the parents of the study subject.
o Question: Do patients with a cloacal malformation suffer from genetic
mutations that can be related to their congenital abnormality?

Secondary objectives:
o Evaluate postoperative management of patients with a cloacal malformation
through test results and questionnaire outcomes.
o Evaluate risk of inheritability and cause of onset of cloacal malformations.

The study design is one of a cross-sectional study. The study population will
consist of patients who were born with a cloacal malformation and were treated
in Rotterdam. Participants will spend approximately 4 hours of time to complete
the study. Prior to the hospital visit participants will be asked to complete 3
questionnaires, to keep a two days voiding chart diary, and to collect a urine
sample. During the hospital visit participants will undergo two urologic test.
There will be collected a blood sample from each participants and both her
parents. Finally, all patients who reached puberty will undergo a gynecological
consult followed by a MRI of the pelvic floor. After this, participants can go
home. No further contributions to the study are required.

The risks of participating in this study are minimal. All parts of the study
are proven to be safe. The collection of a blood sample through a venal
punction can be a little annoying. Ultrasound studies as well as a MRI study
are without any side-effects. Participants will not benefit directly from
participating in the study, because there is no therapeutic aim to this study.
Over time participants might benefit because of the re-evaluation of functional
outcome that is done in the study. This, together with the assessment of
quality of life, might lead to a better postoperative follow-up in these
patients. When test results indicate that further investigations are required
participants will be referred to their doctor.