ESPN 50th Annual Meeting

ESPN 2017


 
French cohort of transient antenatal Bartter syndrome with MAGED2 mutations
Anne Legrand 1 Cyrielle Treard 3 Isabelle Roncelin 3 Sophie Dreux 18 Aurelia Bertholet-Thomas 2 Françoise Broux 4 Daniele Bruno 5 Stéphane Decramer 6 Loïc De Parscau 7 Djamal Djeddi 8 Tackwa Khalifeh 9 Vincent Guigonis 19 Brigitte Llanas 10 Denis Morin 11 Gilles Morin 12 François Nobili 13 Christine Pietrement 14 Amélie Ryckewaert 15 Remi Salomon 16 Rosa Vargas-Poussou 17

1- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique and Université Paris Descartes, Faculté de Médecine, Paris, France.
2- Néphrogones, Centre de Référence des Maladies Rénales Rares, Lyon, France. Hospices Civils de Lyon, Hôpital Femme Mère Enfant, Service de Néphrologie Rhumatologie Dermatologie Pédiatriques, Lyon, France.
3- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique, Paris, France
4- Centre Hospitalier Universitaire Charles Nicolle, Département de Pédiatrie Médicale, Rouen, France.
5- Assistance Publique des Hôpitaux de Marseille, Hôpital de la Timone, Unité de Néphrologie Pédiatrique, Marseille, France.
6- SORARE Centre de Référence des Maladies Rénales Rares du Sud-Ouest and Hôpital de Toulouse, Université Paul Sabatier, Département de Pédiatrie, Toulouse, France.
7- Centre Hospitalier Universitaire de Brest, Service de Pédiatrie et Génétique Médicale, Brest, France.
8- Centre Hospitalier Universitaire Amiens-Picardie, Pédiatrie Médicale, Amiens, France.
9- Centre Hospitalier Universitaire de Poitiers, Service de Pédiatrie, Poitiers, France
10- SORARE Centre de Référence des Maladies Rénales Rares du Sud-Ouest and Centre Hospitalier Universitaire de Bordeaux-GH Pellegrin, Service de Néphrologie Pédiatrique, Bordeaux, France
11- SORARE Centre de Référence des Maladies Rénales Rares du Sud-Ouest and Centre Hospitalier Universitaire de Montpellier, Unité de Néphrologie Pédiatrique, Montpellier, France
12- Centre Hospitalier Universitaire Amiens-Picardie, Service de Génétique, Amiens, France
13- Centre Hospitalier Universitaire de Besançon, Unité de Néphrologie Pédiatrie, Besançon, France
14- Centre Hospitalier Universitaire de Reims, Service de Néphrologie et rhumatologie pédiatriques, Reims, France.
15- Centre Hospitalier Universitaire de Rennes, Service de Néphrologie Pédiatrique, Rennes, France
16- MARHEA, Centre de Référence des Maladies Rénales Héréditaires de l’Enfant et de l’Adulte and Assistance Publique des Hôpitaux de Paris, Hôpital Necker-Enfants-malades, Service de Néphrologie Pédiatrique, Paris, France.
17- MARHEA, Centre de Référence des Maladies Rénales Héréditaires de l’Enfant et de l’Adulte andAssistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique, Paris, France
18- Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Biochimie-Hormonologie, AP-HP, Paris 75019, France
19- SORARE Centre de Référence des Maladies Rénales Rares du Sud-Ouest and Service de pédiatrie, CHU Limoges, Limoges Cedex, France
 
Introduction:

MAGED2 was recently identified in an X-linked severe and transient form of antenatal Bartter’s syndrome associated with polyhydramnios and prematurity as well as in idiopathic polyhydramnios in the male offspring. An inappropriate expression of the sodium-chloride transporters NKCC2 and NCC is disclosed.

 

Material and methods:

MAGED2 was screened by Sanger Sequencing in a series of 42 cases with transient or antenatal Bartter’s syndrome and no pathogenic variant in SLC12A1, KCNJ1, CLCNKB and BSND genes.

 

Results:

We found 17 symptomatic cases from 16 families harboring MAGED2 variants including: three nonsense, three missense, three frameshift, three splice-site, two small in frame deletions and one complete deletion of MAGED2 gene. Only two variants were previously reported, p.Arg446Cys and p.Ala490_Ala493del.

Severe polyhydramnios occurred in all pregnancies, between 18 to 27 weeks of gestation requiring serial amniocentesis (one to eleven) and indomethacin treatment in 5 cases. One case resulted in medical termination of pregnancy. In four cases, polyhydramnios was present in previous or later pregnancies.  All the infants (16) were born preterm with gestational age at delivery between 26 and 33 weeks. All presented a Bartters syndrome with severe polyuria (median diuresis was 15 mL/kg/h).

Surprisingly, two cases were female. The severity of their phenotype and the course of the disease were comparable to those for male and are explained by a selective inactivation of chromosome X.

The medical follow-up of 14 patients revealed that the salt and water losses were resolved between 2 and 18 months: end of indomethacin treatment (6 cases) and/or water and salts supplements. Two cases, with associated disorders died at 1 and 12 months.

 

Conclusions:

We confirmed with our French series of 17 MAGED2 cases the phenotypic presentation of this transient antenatal Bartters syndrome. This new syndrome has to be considered in the differential diagnosis of Bartters syndrome with the screening of MAGED2 as part of the molecular diagnosis.