Molecular Basis of Unilateral Condylar Hyperplasia (UCH)

Unilateral condylar hyperplasia or hyperactivity (UCH) is clinically
characterized by varying degrees of mandibular overgrowth. Obwegeser et al.
(1986) described a classification in 3 categories: hemimandibular elongation
(HE), hemimandibular hyperplasia (HH) and a combination of these two (hybrid
form). The expected concomitant skeletal and dental parameters of these
categories can include a class III malocclusion on the affected side with a
chin and midline deviation and cross-bite on the non-affected side, and/or a
malocclusion with canting of the occlusal plane and unilateral open bite at the
affected side without midline deviation respectively. The asymmetrical
development in UCH patients is often attended with functional and aesthetic
problems.
Treatment consists of removal of the growth centre by a partial condylectomy in
case of ongoing activity. Secondary to this or in patients in whom the
hyperactivity ceased, the remaining asymmetry can be corrected by orthognathic
surgery and remodelling reconstruction of the lower face.
To date, there is little information about the clinical characteristics and
demographic features of this group of patients worldwide. No incidence or
prevalence is available. According to a recent, as yet unpublished Dutch study
(Nolte, Becking et al, in preparation) approximately 30 patients with possible
progressive mandibular asymmetry present each year, with confirmation of the
diagnosis UCH in about 10 patients. In general it can be concluded from the
available literature that UCH can occur at any age with a predilection for
early twenties, and that UCH tends to occur more often in females. It seems
there is no preference for left or right affected side, and no association
between laterality of UCH and gender is found.

Several options have been mentioned to explain the nature of this disease such
as inflammation, trauma, endocrine imbalance, hypervascularity, neoplasms and
genetic factors (Saridin et al., 2009). None of these however are confirmed by
evidence based research. Basically, a congenital origin of the disease,
especially a genetic defect has not been investigated so far.
We hypothesize that in at least part of the patients with UCH the cause is a
somatic mutation in a gene that controls cell growth, such as PTEN or all genes
acting in the AKT pathway, or PIK3CA-associated segmental overgrowth (eg.
Klippel-Trenauney syndrome). Such mechanism has been proven for other entities
showing localized overgrowth of tissue such as Proteus syndrome (Lindhurst et
al., 2011), hemimegalencephaly (Poduri et al, 2012) and Parry-Romberg syndrome
(Hennekam, Lachmeijer et al., unpublished).
The present study is aimed to evaluate this in a small number of patients, and
perform next generation sequencing techniques in both fibroblasts derived from
the affected condyle of the jaw and from leukocytes, and search for differences
between the exomes from the two tissues.

Our aim is to find the cause of UCH. The subsequent aim is to study the
pathogenesis of the entity. The final aim is to find an effective management
for the disorder.

Observational study with no invasive measurements

no risks
blood sampling will be performed during surgery that is already scheduled, from
existing access to the venous system
tissue research is performed on mandibular condyle that will be already taken
out in general anesthesia for therapeutic reasons

the burden is extremely limited, both blood sampling and bone biopsy are taken
at surgical intervention when the patient is under general anesthesia, we
estimate this to be acceptable.

there is no individual benefit, as explained tot the participants by the
investigators, however if the gene and/or mechanism is found, future
individuals can benefit from the outcome. The (timing of) treatment can be
adjusted and more precise predictions about the course of the condition can be
made.