Background
PIK3CA-related overgrowth syndrome (PROS) include a heterogeneous group of disorders characterized
by segmental overgrowth secondary to somatic mosaic activating variants in PIK3CA. Segmental undergrowth is more uncommon and has been less studied but pathogenic
variants in PIK3CA have also been found. With this in mind, we have noticed a group of patients with
PROS that present an undergrowth component associated with their focal overgrowth.
Methods
Retrospective review of patients with PROS presenting overgrowth of the lower limb
and undergrowth of the ipsilateral first toe was performed.
Results
Six patients were included, 4 female and 2 male with a median age of 16.8 years. All
patients presented a PROS phenotype with overgrowth of the lower limb and undergrowth
of ipsilateral first toe. A PIK3CA pathogenic variant was confirmed in all patients. Patients underwent multiple treatments,
currently all are receiving alpelisib with a mean duration of 15.8 months (1–39) and
partial response in lipomatosis and vascular anomalies but no response in overgrowth
and undergrowth so far.
Conclusions
Pathogenic variants in the same gene can create different phenotypes depending on
the time and place of the mutation. There is little information regarding opposing
phenotpyes in the same patient with PROS. The presence of undergrowth in our series
might be explained by genetic, embryogenic, maternal, or placental factors but needs
to be further investigated.
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Article Info
Publication History
Published online: July 21, 2022
Accepted:
June 27,
2022
Received:
April 14,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Conflict of Interest: The authors declare no competing financial interests.
Data Availability Statement: The data that support the findings of this study are available on request from the corresponding author.
Ethics Statement: The data and samples used in this study were obtained with written informed consent. Patients have consented to the use of photographs in scientific publications. The study was approved by the Ethics Committee at Hospital Universitario La Paz.
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