Conclusion
This is one of only a small number of natural history studies examining
the clinical course of a cohort of patients with PLP1 pathogenic
variants and is unique in that it is limited to subjects withPLP1 gene duplications. This study demonstrated many
commonalities with other studies that have characterized the features of
PMD and other PLP1-related disorders but also some new insights into the
natural history.
There are several limitations of the current study. First, the size of
the cohort is small (n=16), with fewer individuals having completed a
second or third FDS. This limitation is a reflection of the day-to-day
demands that are required in providing time-intensive care for PMD
patients. For this reason, many statistical analyses were not possible.
Given the small sample size, it may be difficult to generalize or
extrapolate a conclusion from this study to a larger population of PMD
patients, particularly given the extensive variability observed within
and between families. Future research utilizing a larger cohort will be
necessary to further clarify the natural history and clinical course of
PMD. This work certainly provides a good foundation that opens a new
window into the natural history of patients with PLP1duplications.
A second limitation arises due to the potential for inconsistency
between measurements, given that some FDS scores were completed via
self-report, and others were completed based on in-person physical
examinations. Additionally, questionnaires were filled out based on the
self-report or report of a parent or guardian. An important strength is
the ability to quantify and analyze the FDS through self-report.
A third limitation was the small number of time points available for
several of the participants, which limited our ability to comment on
whether PMD was progressive. In addition, there were differences in the
number of years of follow-up between participants, and initial
questionnaires and FDS scores were gathered at a wide range of ages.
Finally, there were several sibling pairs analyzed in the study. If the
natural history and clinical course of PMD are assumed to vary less
between members of the same family than it does between members of
different families, the inclusion of multiple members of the same family
in our study has the potential to bias our results.