Overgrowth syndromes and vascular anomalies

Overgrowth syndromes and vascular anomalies

Our team cares for patients of all ages with overgrowth syndromes regardless of their anatomical location.

We offer patients multidisciplinary care covering the various medical and paramedical aspects (occupational therapy, physiotherapy, etc.) of these pathologies. Genetic diagnosis is the central element of therapeutic care, and the Necker-Enfants malades hospital provides the latest generation sequencing techniques to quickly identify the molecular anomaly.

The medical and paramedical teams work in close collaboration with the fundamental research laboratories present on the Necker-Enfants Malades hospital site. This integration of research and clinic allows us to offer personalized and precise medicine.

Thus, we propose for all patients a genetic test in order to have a molecular diagnosis. The genes tested are the following:

AKT1, AKT2, AKT3, BRAF, GNAQ, KRAS, MAP2K1, MTOR, NRAS, PIK3CA, PIK3R1, PIK3R2, RASA1, TEK, TSC1, TSC2, GNA11, GNA14, HRAS, MAP3K3, KRIT1, EPHB4 and PTEN.

If we do not find a mutation, we continue our investigations with an exome (exploration of all DNA coding sequences).

Keywords: CLOVES, Proteus, Klippel Trenaunay, Macrodactyly, Megalencephaly, MCAP, MCM, PIK3CA, AKT1, AKT2, AKT3, mTOR

Medical
team

Photo Canaud new hypercroissance

Pr Guillaume Canaud
MD, PhD

Contact us
 

Phone. +33 (0)1 44 38 17 73

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You can also fill out an online form. The team will get back to you as soon as possible.

To prepare your consultation :
please bring the genetic, medical, radiological, surgical documents available

Overgrowth syndromes are defined by an asymmetry that can affect any part of the body, including the brain (called megalencephaly). These syndromes are secondary to congenital genetic abnormalities responsible for an increase in size but also in the number of cells in the body.

The responsible genes are increasingly being identified and are the subject of intense research. For most of these pathologies, the mutation appears during embryonic development and depending on the stage of development at which the mutation occurs, the clinical presentation varies.

All tissues can be affected (fat, vessels, muscle, bone…) and participate in the great variability of manifestations. Because of this great diversity of symptoms, many specialists may be confronted with them (dermatologists, geneticists, orthopedic surgeons, maxillofacial surgeons, visceral surgeons…), hence the need for multidisciplinary care. This multidisciplinarity is offered at the Necker-Enfants malades hospital where patients will meet the different specialists.

Pr Guillaume Canaud, head of the Translational and Molecular Medicine Unit (TMMU)

Radiology

  • Dr Laureline Berteloot
  • Pr Nathalie Boddaert
  • Dr Chalres-Joris Roux
  • Dr Antoine Fraissenon (Hôpital Femme Mère Enfants, Hospices Civils de Lyon)
  • Pr Laurent Guibaud (Hôpital Femme Mère Enfants, Hospices Civils de Lyon)

ENT

  • Pr Nicolas Leboulanger
  • Pr Vincent Couloigner
  • Pr Françoise Denoyelle
  • Pr Noël Garabedian
  • Dr Briac Thierry

Maxillofacial

  • Pr Arnaud Picard
  • Dr Véronique Soupre
  • Pr Roman Khonsari
  • Dr Eleonora Segna

Genetics

  • Pr Jeanne Amiel
  • Pr Valérie Cormier-Daire
  • Pr Stanislas Lyonnet
  • Dr Anne Guimier
  • Dr Geneviève Baujat

Oncogenetics laboratory

  • Pr Vahid Asnafi
  • Dr Sophie Kaltenbach
  • Dr Patrick Villarese

Visceral surgery

  • Pr Sabine Sarnacki-Feray
  • Pr Thomas Blanc

Neurology

  • Pr Nadia Bahi Buisson

Ophthalmology

  • Pr Mathieu Robert

Endocrinology

  • Pr Michel Polak
  • Dr Alix Besancon

Gynecology

  • Dr Sabrina Da Costa

Anatomico-pathological laboratories

  • Pr Jean-Paul Duong
  • Dr Sylvie Fraitag

Orthopedics

  • Pr Stéphanie Pannier
  • Dr Arielle Salon
  • Dr Stéphane Guero

Physiotherapy and rehabilitation medicine

  • Dr Michel Lemoine

Neurosurgery

  • Pr Thomas Blauwblomme
  • Dr Sandro Benichi
  • Dr Marie Bourgeois

Pharmacy

  • Dr Christine Broissand

Imagine genomics platform

  • Dr Christine Bole
  • Dr Mohammed Zarhate

Our goal is to understand the pathophysiology and discover new treatments for rare diseases involving the PIK3CA/AKT/mTOR signaling pathway.

The laboratory is located at the Necker-Enfants malades hospital (Paris) within the Institut Necker-Enfants malades (INEM).

For more informations: http://canaudlab.recherche.parisdescartes.fr 

Our research work is supported by the European Commission (Starting Grant from the European Research Council – PAPA_Study project and Proof of Concept from the European Research Council – CureTheCloves project) but also by many foundations.

An annual meeting will be organized to share the results obtained thanks to the support of our donors.

Guillaume Canaud, winner of the ERC consolidator 2020 call for projects

On December 9, 2020, the European Research Council (ERC) published the results of its €655 million call for « consolidator » projects, dedicated to mid-career researchers. France has 34 winners this year, including three members of the University of Paris : Guillaume Canaud, Frédéric Moynier and Matthew Morrow. Each of the winners receives a €2 million grant for a period of 5 years to facilitate the progress of their research program.

Guillaume Canaud, professor at the University of Paris
ERC Consolidator Grant Winner: « PIK3CA-Related Overgrowth Syndrome, Pluripotency, Expression in speCific Tissue and Secretion « * This basic research project focuses on the role of the PIK3CA gene and protein. PIK3CA is mutated in CLOVES syndrome and all related syndromes.

« Obtaining this award will allow us to continue our studies in the mouse model. We will create multiple mouse lines with PIK3CA mutation in specific tissues such as lymphatic, venous, arterial, fatty tissues, bones or peripheral nerves, in order to better understand the role of each tissue in the development of the disease » explains Guillaume Canaud.

Working on this model should achieve three major objectives: to identify markers of disease activity, to find new therapeutic targets, and to understand the role of PIK3CA during cell differentiation and more precisely its role in cell plasticity.

« Finally, new perspectives in oncology are now envisaged because PIK3CA mutations are also frequent in the development of cancers. Our advances should therefore be able to be extrapolated to oncology, » he concludes.

*This is the third ERC obtained after an ERC Starting Grant obtained in 2015 and an ERC Proof of Concept

The "Gagna A. & Ch. Van Heck prize for incurable diseases - 2021" has been awarded to Professor Guillaume Canaud

This prize of 75.000 €, awarded by the Fund for Scientific Research (F.R.S.-FNRS), is a triennial and international prize, intended to reward a researcher or doctor whose work will have contributed to the cure of a disease still incurable to date, or whose research leads to the hope of a close cure.

The 2021 prize has been awarded to Professor Guillaume Canaud, from the Necker hospital, University of Paris (France), for his contributions to the therapy of a spectrum of overgrowth syndromes characterized by the presence of genetic alterations in a gene called PIK3CA and grouped under the acronym of PROS (PIK3CA-related overgrowth syndrome).

From the clinical standpoint, these conditions are highly diverse, including malformations of the vascular tree, of the adipose tissue and of the bone. From the genetic standpoint, they are caused by activating mutations in a gene called PIK3CA, which codes for a molecule (PI3K) regulating cell growth. No therapy was available for these patients, who often required mutilating surgery.

Based on his knowledge of the molecular mechanisms underlying the disease, Dr Canaud put forward the idea that inhibitors of the PI3K complex, which are used for certain types of cancer patients, could be employed for these patients. The results of a pilot trial on 19 patients indicated significant clinical benefit to all patients, with dramatic improvement of symptoms.

This success story underlines the importance of doctors-scientists who build on the knowledge of how a disease develops to devise novel therapeutic strategies.

2022

Treatment of two infants with PIK3CA-related overgrowth spectrum by alpelisib
Gabriel Morin, Caroline Degrugillier-Chopinet, Marie Vincent, Antoine Fraissenon, Hélène Aubert, Célia Chapelle, Clément Hoguin, Françoise Dubos, Benoît Catteau, Florence Petit, Aurélie Mezel, Olivier Domanski, Guillaume Herbreteau, Marie Alesandrini, Nathalie Boddaert, Nathalie Boutry, Christine Broissand, Tianxiang Kevin Han, Fabrice Branle, Sabine Sarnacki, Thomlas Blanc, Laurent Guibaud, Guillaume Canaud
J Exp Med (2022) 219 (3): e20212148, https://doi.org/10.1084/jem.20212148

2021

Alpelisib administration reduced lymphatic malformations in a mouse model and in patients
Florence Delestre, Quitterie Venot, Charles Bayard, Antoine Fraissenon, Sophia Ladraa, Clément Hoguin, Célia Chapelle, Junna Yamaguchi, Rubina Cassaca, Lola zerbib, Sato Magassa, Gabriel Morin, Vahid Asnafi, Patrick Villarese, Sophie Kaltenbach, Sylvie Fraitag, Jean-Paul Duong, Christine Broissand, Olivia Boccara, Véronique Soupre, Bernard Bonnotte, Caroline Chopinet, Tristan Mirault, Christophe Legendre, Laurent Guibaud and Guillaume Canaud
Science translational medicine, 6 Oct 2021, Vol 13, Issue 614, DOI: 10.1126/scitranslmed.abg0809

– Treatment strategies for mosaic overgrowth syndromes of the PI3K-AKT-mTOR pathway
Gabriel Morin, Guillaume Canaud
British Medical Bulletin, 17 September 2021, ldab023, https://doi.org/10.1093/bmb/ldab023

– A review of mechanisms of disease across PIK3CA-related disorders with vascular manifestations
Guillaume Canaud, Adrienne M. Hammill, Denise Adams, Miikka Vikkula & Kim M. Keppler-Noreuil
Orphanet Journal of Rare Diseases, 08 July 2021

2018

Targeted therapy in patients with PIK3CA-related overgrowth syndrome
Quitterie Venot, Thomas Blanc, Smail Hadj Rabia, Laureline Berteloot, Sophia Ladraa, Jean-Paul Duong, Estelle Blanc, Simon C. Johnson, Clément Hoguin, Olivia Boccara, Sabine Sarnacki, Nathalie Boddaert, Stephanie Pannier, Frank Martinez, Sato Magassa, Junna Yamaguchi, Bertrand Knebelmann, Pierre Merville, Nicolas Grenier, Dominique Joly, Valérie Cormier-Daire, Caroline Michot, Christine Bole-Feysot, Arnaud Picard, Véronique Soupre, Stanislas Lyonnet, Jeremy Sadoine, Lotfi Slimani, Catherine Chaussain, Cécile Laroche-Raynaud, Laurent Guibaud, Christine Broissand, Jeanne Amiel, Christophe Legendre, Fabiola Terzi & Guillaume Canaud
Nature, 2018 Jun, PMID: 29899452 PMCID: PMC7610773 DOI: 10.1038/s41586-018-0217-9

2022

Guillaume Canaud awarded by the FNRS
Z-Science | 06.08.2022
Every three years, the FNRS awards the international « GAGNA A. & Ch. VAN HECK PRIZE FOR INCURABLE DISEASES », to a scientist for a research work that has contributed to the treatment of a currently incurable disease, or that has raised hopes for a cure of the disease. The 2021 winner has just received this prestigious prize in Brussels : Guillaume Canaud, professor at the Université Paris Cité and head of the overgrowth syndromes and vascular anomalies reference center at the Necker-Enfants malades hospital in Paris. This was an opportunity for him to present his research in Z-Science.
> Read more

Rare diseases : Inserm Transfert announces the signature of a licensing agreement with Novartis
Mypharma-editions | 05.17.2022
Inserm Transfert has just announced the signature of a licensing agreement with Novartis for the work resulting from the research of Pr Guillaume Canaud’s team at the Institut Necker-Enfants malades (INEM), of which Inserm is one of the supervisors.
> Read more

Disharmonious overgrowth: encouraging results around a treatment tested on two infants
Franceinfo | 01.26.2022
A team made up of researchers from Inserm, AP-HP, University of Paris, and the Institut Necker-Enfants Malades have communicated the encouraging results of a treatment on two infants suffering from disharmonious overgrowth syndrome .
> Read more

Breast cancer drug shows promise in treating young infants with PIK3CA-related overgrowth spectrum
News medical | 01.26.2022
PIK3CA-related overgrowth spectrum (PROS) is a group of rare, incurable disorders caused by mutations in the PIK3CA gene that result in the malformation and overgrowth of various parts of the body. A new report to be published January 26 in the Journal of Experimental Medicine (JEM) describes the successful treatment of two young infants with PROS using the breast cancer drug alpelisib.
> Read more

Cancer drug shows promise in treating infants with rare disease that causes tissue overgrowth
Medical Xpress | 01.26.2022
PIK3CA-related overgrowth spectrum (PROS) is a group of rare, incurable disorders caused by mutations in the PIK3CA gene that result in the malformation and overgrowth of various parts of the body. A new report to be published January 26 in the Journal of Experimental Medicine (JEM) describes the successful treatment of two young infants with PROS using the breast cancer drug alpelisib.
> Read more

Cancer drug reveals promise in treating infants with rare disease that causes tissue overgrowth
Mirage news | 01.26.2022
PIK3CA-related overgrowth spectrum (PROS) is a group of rare, incurable disorders caused by mutations in the PIK3CA gene that result in the malformation and overgrowth of various parts of the body. A new report to be published January 26 in the Journal of Experimental Medicine (JEM) describes the successful treatment of two young infants with PROS using the breast cancer drug alpelisib.
> Read more

Medicamento contra el cáncer se muestra prometedor en el tratamiento de bebés con enfermedad incurable que causa el crecimiento excesivo de tejido
Nuevo Periodico | 01.26.2022
PIK3CAEl espectro de sobrecrecimiento relacionado (PROS, por sus siglas en inglés) es un grupo de trastornos raros e incurables causados ​​por mutaciones en el PIK3CA gen que resulta en la malformación y el crecimiento excesivo de varias partes del cuerpo. Un nuevo informe que se publicará hoy (26 de enero de 2022) en el Revista de Medicina Experimental (JEM) describe el tratamiento exitoso de dos bebés pequeños con PROS utilizando el medicamento contra el cáncer de mama alpelisib.
> Read more

Cancer drug shows promise in treating infants with rare disease that causes tissue overgrowth
EurekAlert! | 01.26.2022
PIK3CA-related overgrowth spectrum (PROS) is a group of rare, incurable disorders caused by mutations in the PIK3CA gene that result in the malformation and overgrowth of various parts of the body. A new report to be published January 26 in the Journal of Experimental Medicine (JEM) describes the successful treatment of two young infants with PROS using the breast cancer drug alpelisib.
> Read more

Cancer Drug Shows Promise in Treating Infants With Incurable Disease That Causes Tissue Overgrowth
Scitechdaily | 01.26.2022
PIK3CA-related overgrowth spectrum (PROS) is a group of rare, incurable disorders caused by mutations in the PIK3CA gene that result in the malformation and overgrowth of various parts of the body. A new report to be published today (January 26, 2022) in the Journal of Experimental Medicine (JEM) describes the successful treatment of two young infants with PROS using the breast cancer drug alpelisib.
> Read more

Противораковый препарат помог детям с деформированными ногами начать ходить
N+1 | 01.26.2022
Французские врачи значительно облегчили состояние детей с генетической болезнью, при которой деформируются конечности и внутренние органы. Медики давали младенцам противораковый препарат, ингибирующий белковый продукт поломанного гена. Спустя год после начала лечения у детей уменьшился размер деформированных ног, и конечности стали лучше сгибаться, что позволило детям начать ходить с поддержкой взрослых. О прогрессе лечения врачи рассказали в Journal of Experimental Medicine.
> Read more

癌症药物在治疗患有导致组织过度生长的不治之症的婴儿中显示出前景
CN Beta | 01.27.2022
PIK3CA相关过度生长谱(PROS)是一组由PIK3CA基因突变引起的罕见、无法治愈的疾病,导致身体各部分畸形和过度生长。2022年1月26日发表在《实验医学杂志》(JEM)上的一份新报告描述了如何使用乳腺癌药物alpelisib成功治疗两名患有PROS的婴儿
> Read more

2021

Matière Grise : Cloves syndrome
RTBF | 05.30.2021

Report of the program Matière Grise on Cloves syndrome with the participation of Pr Guillaume Canaud. Patients testify about the changes obtained thanks to an inhibitor called BYL719, developed by Pr Guillaume Canaud and his teams.


« Elephant man » syndrome: towards a better management?
Handicap.fr | 05.01.2021
The disharmonious overgrowth syndromes cause physical deformations, more or less disabling depending on the case. Researchers are developing a unique consortium to improve their care and identify new treatments.
Lire la suite >

2019

Two Paris Descartes researchers distinguished by the City of Paris
Paris Descartes university | 5.28.2019
The 2018 Grand Prix de la ville de Paris for Medicine and Medical Research were awarded to Jean-Laurent Casanova (Paris Descartes university – INSERM U1163 – Institut Imagine) and Guillaume Canaud (Paris Descartes university – INSERM U1151 – Institut Necker-Enfants malades).
Read more >

I have a monster in my arm
LeMonde.fr | Fiamma Luzzati’s science blog | 4.18.2019
We all have a hidden side, a side that we don’t show for fear of being judged.
Read more >

2018

Guillaume Canaud winner of the Jean-Pierre Lecocq award
Paris-Descartes university | 10.17.2018
Guillaume Canaud, university lecturer and hospital practitioner, adult nephrologist at the Necker-Enfants malades hospital (AP-HP, Paris Descartes university) is the winner with Anne Houdusse of the 2018 Jean-Pierre Lecocq grand prize of the French academy of sciences.
Read more >

Cloves syndrome: « Our children are not freaks ».
La Croix | 6.19.2018
An important breakthrough has just been announced against a rare genetic disease that many media have disrespectfully chosen to call « Elephant Man syndrome ».
Read more >

The spectacular French success against a deforming genetic disease
Le Figaro | 8.29.2018
A world first took place at Necker Hospital for patients with a rare syndrome causing severe deformities.
Read more >

Targeted therapy in patients with PIK3CA-related overgrowth syndrome
Medicalpress | 15.6.2018
Dr. Guillaume Canaud at the Necker-Enfants malades hospital and his team recently demonstrated the efficacy of a specific inhibitor called BYL719 in a cohort of 19 patients suffering from congenital lipomatous overgrowth-vascular malformation-epidermal nevi-spinal anomaly syndrome (CLOVES) and similar disorders. This medication is currently undergoing therapeutic oncology trials (phase I/II). No significant side effects have been observed 18 months after commencement of treatment. This study, published in the journal Nature, is an example of precision medicine and demonstrates the major benefits of this therapeutic strategy for these patients, who show significantly improved health and quality of life.
Read more >

Elephant Man: an anticancer drug reduces deformities of Cloves syndrome
Pourquoi Docteur ? | 6.16.2018
Like Elephant Man’s disease, Cloves syndrome is a closely related genetic abnormality that causes accelerated deformities of organs and limbs. French researchers have tested a specific inhibitor against the gene responsible for this rare disease: PIK3CA. Tried on 19 patients, the inhibitor is also being developed in blood diseases, and has shown spectacular effects.
Read more >

French medical first: an effective treatment for Cloves syndrome
Le Quotidien du Médecin | 6.14.2018
A cohort of 19 patients suffering from CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal naevi, scoliosis/skeletal and spinal syndrome) benefited from the first oral treatment of this pathology: BYL719. Initially, this molecule was developed by Novartis and is used in several cancer indications: melanoma, squamous cell carcinomas of the head and neck, breast cancer, ovarian cancer, etc.
Read more >

French researchers discover a treatment for a strange disease that deforms organs
Sciences et Avenir | 6.14.2018
Similar to the « Elephant man » disease, Cloves syndrome causes anarchic growth of certain parts of the body and affects an estimated 1,000 patients in France. Researchers have discovered an effective treatment for this pathology that has remained mysterious for a long time.
Read more >

Syndrome similar to « Elephant Man »: a simple tablet to treat it?
Le Progrès | 6.14.2018
French researchers have succeeded in treating several people with Cloves syndrome, which causes deformed growth of certain organs, thanks to a treatment containing a simple molecule.
Read more >

Cloves syndrome: a simple tablet effective against this rare genetic disease
RTL | 6.14.2018
Spectacular transformations have been observed thanks to this tablet on patients affected by this disease which deforms organs or even parts of the body.
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Elephant Man Syndrome: At last there is hope for a treatment
Le Parisien | 6.13.2018
Growths deformed their bodies. They melted in 19 patients thanks to a new treatment discovered by a French doctor. A world first. Several patients tell us about their « rebirth ».
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Medical premiere: CLOVES syndrome and overgrowth syndromes
Paris-Descartes university | 6.13.2018
CLOVES syndrome and overgrowth syndromes: remarkable improvement in the health status of 19 children and adult patients thanks to a new therapeutic strategy.
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A medical first: remarkable improvement in the health status of 19 child and adult patients with CLOVES syndrome.
Communiqué de presse AP-HP | 6.13.2018
Dr. Guillaume Canaud and his team have just demonstrated the efficacy of a new molecule, BYL719, in 19 patients followed at the Necker-Enfants malades – AP-HP hospital and suffering from CLOVES syndrome (Congenital Lipomatous Overgrowth, Vascular Malformation, Epidermal Nævi) or related disorders. This drug is currently undergoing therapeutic trials in oncology (Phase I/II).
No significant side effects have been observed 18 months after the start of treatment.
Read more >