Abstract
Objectives
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, four female and two 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.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Annals of Vascular SurgeryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation.Am J Med Genet A. 2015; 167A: 287-295
- Sirolimus in the Treatment of Vascular Anomalies.Eur J Pediatr Surg. 2017; 27: 86-90
- Sirolimus for the treatment of complicated vascular anomalies in children.Pediatr Blood Cancer. 2011; 57: 1018-1024
- Targeted therapy in patients with PIK3CA-related overgrowth syndrome.Nature. 2018; 558: 540-546
- Hemangiomatosis braquial osteolitica.Angiologia. 1949; 1: 1
- Des angiomes veineux (about venous angiomas).Arch Mal Couer. 1948; 41: 436-438
- Segmental undergrowth is associated with pathogenic variants in vascular malformation genes: A retrospective case-series study.Clin Genet. 2022; 101: 296-306
- CLAPO syndrome: identification of somatic activating PIK3CA mutations and delineation of the natural history and phenotype.Genet Med. 2018; 20: 882-889
- A review of mechanisms of disease across PIK3CA-related disorders with vascular manifestations.Orphanet J Rare Dis. 2021; 16: 306
- Inverse Klippel-Trenaunay syndrome: review of cases showing deficient growth.Dermatology. 2007; 214: 130-132
- Capillary-venous malformation in the lower limb.Pediatr Dermatol. 2013; 30: 541-548
- PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution.JCI Insight. 2016; 1: e87623
- A six-attribute classification of genetic mosaicism.Genet Med. 2020; 22: 1743-1757
- Clinical delineation and natural history of the PIK3CA-related overgrowth spectrum.Am J Med Genet A. 2014; 164A: 1713-1733
- Multiscale modeling of vertebrate limb development.Wiley Interdiscip Rev Syst Biol Med. 2020; 12: e1485
- Human limb malformations; an approach to the molecular basis of development.Int J Dev Biol. 2002; 46: 983-991
- Noninvasive Diagnostic Methods for Better Screening of Peripheral Arterial Disease.Ann Vasc Surg. 2018; 52: 263-272
- Alpelisib Treatment for Genital Vascular Malformation in a Patient with Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, and Spinal/Skeletal Anomalies and/or Scoliosis (CLOVES) Syndrome.J Pediatr Adolesc Gynecol. 2019; 32: 648-650
Article Info
Publication History
Accepted:
June 27,
2022
Received in revised form:
June 2,
2022
Received:
April 14,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Elsevier Inc. All rights reserved.
