Fetal phenotypes in otopalatodigital spectrum disorders.
Clin Genet. 2015-10-29; 89(3): 371-377
DOI: 10.1111/cge.12679
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1. Clin Genet. 2016 Mar;89(3):371-7. doi: 10.1111/cge.12679. Epub 2015 Oct 29.
Fetal phenotypes in otopalatodigital spectrum disorders.
Naudion S(1), Moutton S(1)(2), Coupry I(2), Sole G(2)(3), Deforges J(1),
Guerineau E(2), Hubert C(4), Deves S(1), Pilliod J(2), Rooryck C(1)(2), Abel
C(5), Le Breton F(6), Collardeau-Frachon S(7), Cordier MP(8), Delezoide AL(9),
Goldenberg A(10), Loget P(11), Melki J(12), Odent S(13), Patrier S(14), Verloes
A(15), Viot G(16), Blesson S(17), Bessières B(18), Lacombe D(1)(2), Arveiler
B(1)(2), Goizet C(1)(2), Fergelot P(1)(2)(4).
Author information:
(1)CHU Bordeaux, Centre de Référence des Anomalies du Développement Embryonnaire,
Service de Génétique Médicale, Bordeaux, France.
(2)University Bordeaux, Laboratoire Maladies Rares, Génétique et Métabolisme
(MRGM), Bordeaux, France.
(3)CHU Bordeaux, Fédération des Neurosciences Cliniques, Bordeaux, France.
(4)Plateforme Génome Transcriptome, Centre de Génomique Fonctionnelle de
Bordeaux, Université de Bordeaux, Bordeaux, France.
(5)CHU Lyon, Service de Génétique, Hôpital Femme Mère Enfant, Hospices Civils de
Lyon, Lyon, France.
(6)CHU Lyon, Service de Pathologie du Nord, Hôpital de la Croix-Rousse, Lyon,
France.
(7)CHU de Lyon, Centre de Pathologie Est, Hospices Civils de Lyon, Lyon, France.
(8)CHU Lyon, Service de Génétique Médicale, Hôpital Mère Enfant, Lyon, France.
(9)APHP, Service de Biologie du Développement, Hôpital Robert Debré, Paris,
France.
(10)CHU Rouen, Service de Génétique Médicale, Rouen, France.
(11)CHU Rennes, Service d’Anatomie Cytologie Pathologique, Rennes, France.
(12)INSERM U78, Laboratoire de Neurogénétique Moléculaire, Université de Paris
XI, Paris, France.
(13)CHU de Rennes, Service de Génétique Clinique, Centre de Référence Anomalies
du Développement CLAD-Ouest, Hôpital Sud, Rennes, France.
(14)CHU Rouen, Service d’Anatomie Pathologique, Rouen, France.
(15)Département de Génétique, APHP-Hôpital universitaire Robert Debré, Université
Sorbonne Paris-Cité, Faculté de Médecine Denis Diderot-Paris 7, and INSERM UMR
1141, Paris, France.
(16)APHP, Service de Génétique Médicale, Maternité Port-Royal, Paris, France.
(17)CHRU Tours, Service de Génétique, Hôpital Bretonneau, Tours, France.
(18)APHP, Service Histo-Embryologie et Cytogénétique, Hôpital Necker, Paris,
France.
Otopalatodigital spectrum disorders (OPDSD) include OPD syndromes types 1 and
type 2 (OPD1, OPD2), Melnick-Needles syndrome (MNS), and frontometaphyseal
dysplasia (FMD). These conditions are clinically characterized by variable
skeletal dysplasia associated in males, with extra-skeletal features including
brain malformations, cleft palate, cardiac anomalies, omphalocele and obstructive
uropathy. Mutations in the FLNA gene have been reported in most FMD and OPD2
cases and in all instances of typical OPD1 and MNS. Here, we report a series of
10 fetuses and a neonatally deceased newborn displaying a multiple congenital
anomalies syndrome suggestive of OPDSD and in whom we performed FLNA analysis. We
found a global mutation rate of 44%. This series allows expanding the clinical
and FLNA mutational spectrum in OPDSD. However, we emphasize difficulties to
correctly discriminate OPDSD based on clinical criteria in fetuses due to the
major overlap between these conditions. Molecular analyses may help pathologists
to refine clinical diagnosis according to the type and the location of FLNA
mutations. Discriminating the type of OPDSD is of importance in order to improve
the genetic counseling to provide to families.
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
DOI: 10.1111/cge.12679
PMID: 26404489 [Indexed for MEDLINE]