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

Gutiérrez, Juan Carlos López; Lizarraga, Rocío; Delgado, C Alfredo; Urrutia, María José Martínez; Díaz, Mercedes; Miguel, Mario; Triana, Paloma

doi:10.1016/j.jpag.2019.07.003

Cited by 48 publications

(36 citation statements)

References 8 publications

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“…Of note, BYL719 has entered phase I-II clinical trials to evaluate its efficacy and safety in patients with various PIK3CA-implicated solid tumors [17-19]. Recently, López Gutiérrez et al [20] reported a 17-year-old girl with CLOVES syndrome who had large vascular malformations involving the external genitalia. The patient was initially administered oral rapamycin for 12 months.…”

Section: Discussionmentioning

confidence: 99%

CLOVES Syndrome in a Nine-month-old Infant

Alomar

Khedr

Alajlan

2019

Cureus

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CLOVES syndrome is a recently described overgrowth syndrome. Clinically, it is characterized by congenital lipomatous overgrowth (CLO), vascular anomalies (V), epidermal nevi (E), and skeletal deformities (S). Genetically, it is characterized by a somatic gain-of-function mutation of the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. This somatic mutation is, in turn, associated with the activation of the protein kinase Bmammalian target of the rapamycin (AKT-mTOR) pathway that drives various signaling cascades. The end result is eventually promoting cell proliferation, growth, and survival. CLOVES syndrome is exceedingly uncommon, with less than 200 cases currently documented. Herein, we describe a case of CLOVES syndrome in a nine-month-old male infant who was referred to our dermatology clinic for further assessment and management. The diagnosis was made based on clinical findings and confirmed by genetic testing.

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Section: Discussionmentioning

confidence: 99%

CLOVES Syndrome in a Nine-month-old Infant

Alomar

Khedr

Alajlan

2019

Cureus

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“…A 17-year-old female patient with severe genital damage was first treated with rapamycin for one year without significant improvement and then treated with BYL719. Her condition then improved markedly allowing surgical reconstruction [19].…”

Section: Alpesilibmentioning

confidence: 99%

“…Une patiente de 17 ans avec de sévères atteintes aux parties génitales a été d'abord traitée avec de la rapamycine pendant un an sans amélioration notable puis traitée au BYL719. Son état s'est alors nettement amélioré permettant une reconstruction chirurgicale [19].…”

Section: Alpesilibunclassified

PIK3CA-related overgrowth spectrum: animal model and drug discovery

Venot

Canaud

2021

Comptes Rendus. Biologies

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Quitterie Venot was the award winner of the 2020 prize for Great Advances in Biology from the Académie des sciences / Quitterie Venot a été lauréate du prix 2020 des Grandes Avancées en Biologie de l'Académie des sciences Abstract. This review recapitulates the recent knowledge accumulation on overgrowth syndrome related to gain of function of the phosphoinositide3 kinase (PI3K)-alpha. These disorders, known as PIK3CA related overgrowth syndromes (PROS) are caused by somatic PIK3CA mutation occurring during embryogenesis. We summarize here the currently available animal models and new treatments undergoing development.Résumé. Cette revue détaille un syndrome d'hypercroissance dysharmonieuse récemment identifié : le syndrome d'hypercroissance dysharmonieuse lié à PIK3CA. Ce syndrome est dû à une activation en mosaïque de la voie PI3K-AKT-mTOR. Une mutation activatrice du gène PIK3CA est responsable de l'activation de la voie et des manifestations cliniques associées. Dans cette revue, nous avons répertorié les modèles animaux de ces syndromes ainsi que les traitements en cours d'expérimentation.

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“…Recently, a PIK3CA inhibitor named alpelisib (PIQRAY, Novartis Pharmaceuticals Corporation) was proposed to show e cacy in patients with PROS/CLOVES; this drug is now under investigation in clinical trials. [4,5] Propranolol, a beta-blocker, has been widely used for the treatment of hemangiomas, and several previous studies have suggested that propranolol might negatively regulate the AKT/mTOR pathway. [6-8] Indeed, propranolol has shown partial e cacy in the regression of vascular masses in patients with KTS.…”

Section: Introductionmentioning

confidence: 99%

Clinical and Genetic Analyses and Treatment Outcomes of Patients with Lateralized Overgrowth

Kim

Lee

Choi

et al. 2021

Preprint

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Background: The genetic features and management of lateralized overgrowth have been elusive. This study was performed to investigate the genetic profiles and outcomes of propranolol- or alpelisib-treated patients with lateralized overgrowth. Methods: Fifteen patients with lateralized overgrowth were enrolled. Clinical features and whole-body magnetic resonance imaging (WB-MRI) findings were evaluated. Deep sequencing with a customized gene panel of affected tissue and peripheral white blood cells was performed. Propranolol was administered and clinical outcomes were examined. The PIK3CA inhibitor alpelisib was administered via a managed access program. Results: Genetic testing identified PIK3CA (n=7, 46.7%), KRAS (n=2, 13.3%), PTEN (n=1, 6.7%), MAP2K3 (n=1, 6.7%), GNAQ (n=1, 6.7%), TBC1D4 (n=1, 6.7%), and TEK (n=1, 6.7%) mutations. Propranolol was administered in 12 patients, and 7 experienced limited improvement of symptoms. Alpelisib was administered in two patients with a PIK3CA mutation, and the WB-MRI after 1 year of treatment showed a reduction in proliferated masses. Conclusions: Deep sequencing identified diverse genetic features of lateralized overgrowth. Propranolol could be used as an adjuvant therapy for reducing vascular symptoms, but targeted therapy with a PIK3CA inhibitor would be the primary therapeutic strategy for PIK3CA-related overgrowth syndrome.

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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

Cited by 48 publications

References 8 publications

CLOVES Syndrome in a Nine-month-old Infant

CLOVES Syndrome in a Nine-month-old Infant

PIK3CA-related overgrowth spectrum: animal model and drug discovery

Clinical and Genetic Analyses and Treatment Outcomes of Patients with Lateralized Overgrowth

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