Non-invasive CT screening for pulmonary arteriovenous malformations in children with confirmed hereditary hemorrhagic telangiectasia: Results from two pediatric centers.
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder that is caused by mutations in mainly two genes, that is ENG, encoding endoglin (HHT1), or ACVRL1, encoding activin receptor-like kinase 1 (ALK-1/HHT2). HHT is characterized by recurrent epistaxis, mucocutaneous telangiectasia, and vascular visceral dysplasia responsible for visceral arteriovenous malformations (AVM).



to report the experience of two university hospitals (Trousseau, Paris, and CHIC, Creteil) with screening children for HHT and pulmonary AVM (PAVM) using high resolution computed tomography (HRCT).



parents with confirmed HHT were offered to have their children screened for the mutation identified in their family, and informed consent was obtained. Children carrying the same mutation as their parents underwent HRCT of the chest without contrast.



between 2008 and 2015, 99 children were screened for HHT mutations. Mutations were identified in 59 patients, that is 24 HHT1 and 35 HHT2. Radiologic and clinical screening was possible in 52 patients (21 HHT-1 and 31 HHT-2). Among those, PAVM was identified in 13 patients (25%; n = 8 HHT1; n = 5 HHT2), and four of them required embolization therapy.



This study highlights the usefulness of genetic screening in children with known HHT family. It also suggests that a non-invasive protocol such as HRTC is an efficient approach to detect non-symptomatic lesions that are present early on in children carrying the ENG (HHT1), but also the ACVRL1 mutations (HHT2). Pediatr Pulmonol. 2017;52:642-649. © 2017 Wiley Periodicals, Inc.
Service de Pédiatrie, Centre Hospitalier Intercommunal de Créteil, Créteil 94000, France.
Nurcan
N
Soysal
Département de Génétique, Hôpital Pitié-Salpetrière, UF d'Oncogénétique et d'Angiogénétique Moléculaire, Paris, France.
Mélanie
M
Eyries
Service de Radiologie, Centre Hospitalier Intercommunal de Créteil, Créteil, France.
Suzanne
S
Verlhac
Service d'ORL, Centre Hospitalier Intercommunal de Créteil, Créteil, France.|Inserm, U955, Equipe 5, Créteil 94000, France.|Université Paris-Est, Faculté de Médecine, Créteil 94000, France.
Virginie
V
Escabasse
Service de Pédiatrie, Centre Hospitalier Intercommunal de Créteil, Créteil 94000, France.
Natascha
N
Remus
Service de Pneumologie Pédiatrique, Hôpital Armand-Trousseau, Paris, France.|Centre des Maladies Respiratoires Rares, RESPIRARE®, Paris 75012, France.
Aline
A
Tamalet
Service de Radiologie pédiatrique, Hôpital Bicêtre, Hôpitaux Universitaires Paris-Sud, Assistance Publique Hôpitaux de Paris, Kremlin-Bicêtre, France.
Jean-Yves
JY
Rioux
Service de Radiologie pédiatrique, Hôpital Bicêtre, Hôpitaux Universitaires Paris-Sud, Assistance Publique Hôpitaux de Paris, Kremlin-Bicêtre, France.
Stéphanie
S
Franchi-Abella
Service de Radiologie, Centre Hospitalier Intercommunal de Créteil, Créteil, France.
Manuela
M
Vasile
Sorbonne Universités, UPMC Univ Paris 06, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136).
Sarah
S
Robert
Service de Pédiatrie, Centre Hospitalier Intercommunal de Créteil, Créteil 94000, France.|Inserm, U955, Equipe 5, Créteil 94000, France.|Université Paris-Est, Faculté de Médecine, Créteil 94000, France.
Céline
C
Delestrain
Service de Pédiatrie, Centre Hospitalier Intercommunal de Créteil, Créteil 94000, France.
Isabelle
I
Hau
Service de Radiologie, Hôpital Armand-Trousseau, Paris, France.|Faculté de Médecine Pierre et Marie Curie, Sorbonne Université-UPMC, Paris, France.
Hubert
H
Ducou-Le Pointe
Département de Génétique, Hôpital Pitié-Salpetrière, UF d'Oncogénétique et d'Angiogénétique Moléculaire, Paris, France.
Florent
F
Soubrier
Faculté de Médecine Pierre et Marie Curie, Sorbonne Université-UPMC, Paris, France.|Service de Radiologie, Hôpital Tenon, Paris, France.|Centre de Compétence Maladie de Rendu Osler, Hôpital Tenon, Paris 75020, France.
Marie-France
MF
Carette
Service de Pédiatrie, Centre Hospitalier Intercommunal de Créteil, Créteil 94000, France.|Inserm, U955, Equipe 5, Créteil 94000, France.|Université Paris-Est, Faculté de Médecine, Créteil 94000, France.|Centre des Maladies Respiratoires Rares, RESPIRARE®, Paris 75012, France.|Centre de Compétence Maladie de Rendu Osler, Hôpital Tenon, Paris 75020, France.
Ralph
R
Epaud
D030301:Activin Receptors, Type II / Q000235:genetics; D000293:Adolescent; D001165:Arteriovenous Malformations / Q000150:complications / Q000000981:diagnostic imaging*; D002648:Child; D002675:Child, Preschool; D000071063:Endoglin / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008168:Lung / Q000000981:diagnostic imaging*; D008297:Male; D009154:Mutation; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000150:complications / Q000000981:diagnostic imaging* / Q000235:genetics; D014057:Tomography, X-Ray Computed / Q000379:methods*
D000071063:Endoglin; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II
ACVRL1; ENG; HHT; Rendu-Osler-Weber disease; arteriovenous malformation; children screening; tomodensitometry