National Evaluation of Patients With PIK3CA-Related Overgrowth Spectrum (PROS)

NCT05563831 | Completed DMC

• 1 other identifier: C20-09
• Study Type: observational
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Overgrowth syndromes are rare genetic disorders defined by tissue hypertrophy that can be either localized or generalized, affecting both latitudinal and longitudinal growth. The genes involved in overgrowth syndromes are not well characterized but mostly concern the PIK3CA/AKT/mTOR pathway, a major actor of cell growth and proliferation. The mutations are not inherited but occurs during embryogenesis leading to somatic mosaicism. Owing to the variability of the clinical presentation, their exact prevalence is yet unknown. In order to answer this question, the investigators team create here the first French national registry on overgrowth syndromes.

Conditions

MCAP; PIK3CA-related Overgrowth Spectrum; CLOVES Syndrome; Klippel Trenaunay Syndrome; Megalencephaly; Macrodactyly; Vascular Malformations; Lymphatic Malformation; Venous Malformation

Keywords

PIK3CA; Related Overgrowth Syndrome; PIK3CA/AKT/mTOR pathway; clinical diagnosis; Biobank; Patient Stratification

Outcome Measures

Primary Outcomes (1)

• Description of patients with overgrowth syndromes

  Clinical and molecular characterization of patients with overgrowth syndromes will be performed.

  5 years

Secondary Outcomes (4)

• Prevalence of overgrowth syndromes in France

  5 years

• Biobanking of samples derived from patients with overgrowth syndromes

  5 years

• Description of patient cares: mumber of consultations and hospitalizations, number of treatment lines, grouping of patients by type of course (clusters)

  5 years

• Economic evaluation of cares for patients with overgrowth syndromes: cost of care, per period and cumulative.

  5 years

Interventions

national registry OTHER

The investigators will collect demographic, clinical, biological and imaging characteristics of patients with PROS.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients with overgrowth syndrome referred by their doctors or patients who have sent a consultation request to the Reference Center (https://hopital-necker.aphp.fr/contacts-cloves) will be enrolled.

You may qualify if:

• Affiliated to the French healthcare insurance system.
• Pediatric and adult patients
• Clinical diagnosis of overgrowth syndrome
• Written informed consent from adult patients and from both parents of pediatric patients.

You may not qualify if:

• Person subject to a judicial safeguard measure
• Inability to give informed consent

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (1)

Translational medicine and Targeted therapies unit, Hôpital Necker Enfants Malades

Paris, 75015, France

Location

Related Publications (6)

• Canaud G, Hammill AM, Adams D, Vikkula M, Keppler-Noreuil KM. A review of mechanisms of disease across PIK3CA-related disorders with vascular manifestations. Orphanet J Rare Dis. 2021 Jul 8;16(1):306. doi: 10.1186/s13023-021-01929-8.

  PMID: 34238334 BACKGROUND

• Morin G, Canaud G. Treatment strategies for mosaic overgrowth syndromes of the PI3K-AKT-mTOR pathway. Br Med Bull. 2021 Dec 16;140(1):36-49. doi: 10.1093/bmb/ldab023.

  PMID: 34530449 BACKGROUND

• Delestre F, Venot Q, Bayard C, Fraissenon A, Ladraa S, Hoguin C, Chapelle C, Yamaguchi J, Cassaca R, Zerbib L, Magassa S, Morin G, Asnafi V, Villarese P, Kaltenbach S, Fraitag S, Duong JP, Broissand C, Boccara O, Soupre V, Bonnotte B, Chopinet C, Mirault T, Legendre C, Guibaud L, Canaud G. Alpelisib administration reduced lymphatic malformations in a mouse model and in patients. Sci Transl Med. 2021 Oct 6;13(614):eabg0809. doi: 10.1126/scitranslmed.abg0809. Epub 2021 Oct 6.

  PMID: 34613809 BACKGROUND

• Morin G, Degrugillier-Chopinet C, Vincent M, Fraissenon A, Aubert H, Chapelle C, Hoguin C, Dubos F, Catteau B, Petit F, Mezel A, Domanski O, Herbreteau G, Alesandrini M, Boddaert N, Boutry N, Broissand C, Han TK, Branle F, Sarnacki S, Blanc T, Guibaud L, Canaud G. Treatment of two infants with PIK3CA-related overgrowth spectrum by alpelisib. J Exp Med. 2022 Mar 7;219(3):e20212148. doi: 10.1084/jem.20212148. Epub 2022 Jan 26.

  PMID: 35080595 BACKGROUND

• Venot Q, Blanc T, Rabia SH, Berteloot L, Ladraa S, Duong JP, Blanc E, Johnson SC, Hoguin C, Boccara O, Sarnacki S, Boddaert N, Pannier S, Martinez F, Magassa S, Yamaguchi J, Knebelmann B, Merville P, Grenier N, Joly D, Cormier-Daire V, Michot C, Bole-Feysot C, Picard A, Soupre V, Lyonnet S, Sadoine J, Slimani L, Chaussain C, Laroche-Raynaud C, Guibaud L, Broissand C, Amiel J, Legendre C, Terzi F, Canaud G. Targeted therapy in patients with PIK3CA-related overgrowth syndrome. Nature. 2018 Jun;558(7711):540-546. doi: 10.1038/s41586-018-0217-9. Epub 2018 Jun 13.

  PMID: 29899452 RESULT

• Manning BD, Toker A. AKT/PKB Signaling: Navigating the Network. Cell. 2017 Apr 20;169(3):381-405. doi: 10.1016/j.cell.2017.04.001.

  PMID: 28431241 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Biopsies and tissues removed during surgical procedures will be stored in the Department of Pathology of Hôpital Necker-Enfants Malades (authorization CODECOH n° DC-2020-3940 de la Plateforme de Resource Biologique de l'Hôpital Necker-Enfants Malades). DNA, PBMC and plasma from patients will be stored for further studies. Samples will be stored at the au Centre de Ressources Biologiques de la Structure Fédérative de Recherche Necker (autorisation CODECOH n° DC-2020-3940 du CRB Necker, supervised by Dr. Marie-Alexandra ALYANAKIAN).

MeSH Terms

Conditions

Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi; Klippel-Trenaunay-Weber Syndrome; Megalencephaly; Megalodactyly; Vascular Malformations; Lymphatic Abnormalities; Hereditary Sensory and Autonomic Neuropathies

Condition Hierarchy (Ancestors)

Angiomatosis; Vascular Diseases; Cardiovascular Diseases; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Nervous System Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cardiovascular Abnormalities; Lymphatic Diseases; Hemic and Lymphatic Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn

Study Officials

• Guillaume Canaud, MD,PHD

  Institut National de la Santé Et de la Recherche Médicale, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2022
• First Posted: October 3, 2022
• Study Start: February 21, 2023
• Primary Completion: June 7, 2023
• Study Completion: June 7, 2023
• Last Updated: February 23, 2026

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)