Molecular basis of Parry-Romberg syndrome II

Parry-Romberg syndrome (Romberg syndrome; progressive hemifacial atrophy)
consists of slowly progressive atrophy of bone and the soft tissues of
essentially half the face accompanied most frequently by contralateral
Jacksonian epilepsy, trigeminal neuralgia, and ipsilateral changes in the eyes
and hair. The consequences for the disorder for individual patients are
significant due to the often enormous disfigurement it causes. There is at
present no therapy.
We have limited proof that Parry-Romberg syndrome is a laminopathy in a mosaic
state. In an earlier study in fibroblasts derived from affected facial region
in 3 patients we were able to detect abnormal nuclear morphology (the hall mark
of a laminopathy) which was absent in nuclei from leukocytes, indicating
mosaicism, in three patients. Further molecular studies using next generation
techniques searching for differences between variants in DNA from the affected
area and leukocytes has been performed but the causative gene could not be
detected. The best next way to detect the cause will be to perform studies on
an RNA level, performed in fibroblasts from affected tissue and fibroblasts
from non-affected tissue, and also compare in lymphocytes.

1. Detection of the gene causing Parry-Romberg syndrome.
2. Study of molecular and cellular mechanisms leading to the various
manifestations of Parry-Romberg syndrome.

observational study with invasive measurements

The risk of blood sampling is limited. The burden of a skin biopsy in a healthy
adult with normal cognition is in general minimal if taken from a limb
(unaffected tissue). The burden is higher if the biopsy is taken from affected
tissue, i.e. the face. The site of the biopsy will be chosen together with the
participant and likely will be in the anterior hairline as this is the least
visible. The site will be locally anaesthetized. The biopsy (2 or 3 mm in
diameter) does not need any stitching and will heal spontaneously. We realize
this is a burden to the patients, but without biopsying this part of the skin
it will not be possible to prove the hypothesis and find the causative gene. We
have considered waiting for surgical procedures for patient care purposes in
some patients, but it is at present uncertain whether these will be performed
in the near future. Proving Parry-Romberg syndrome to be laminopathy and
finding the gene would lead to a trial in order to decrease or stop
progression. There is no benefit of participating in this study to the
participants. There is a group benefit as the study should provide essential
information needed for a future intervention study.