Bainbridge-Ropers syndrome caused by loss-of-function variants in ASXL3: a recognizable condition

Abstract : Truncating ASXL3 mutations were first identified in 2013 by Bainbridge et al. as a cause of syndromic intellectual disability in four children with similar phenotypes using whole-exome sequencing. The clinical features - postulated by Bainbridge et al. to be overlapping with Bohring-Opitz syndrome - were developmental delay, severe feeding difficulties, failure to thrive and neurological abnormalities. This condition was included in OMIM as 'Bainbridge-Ropers syndrome' (BRPS, #615485). To date, a total of nine individuals with BRPS have been published in the literature in four reports (Bainbridge et al., Dinwiddie et al, Srivastava et al. and Hori et al.). In this report, we describe six unrelated patients with newly diagnosed heterozygous de novo loss-of-function variants in ASXL3 and concordant clinical features: severe muscular hypotonia with feeding difficulties in infancy, significant motor delay, profound speech impairment, intellectual disability and a characteristic craniofacial phenotype (long face, arched eyebrows with mild synophrys, downslanting palpebral fissures, prominent columella, small alae nasi, high, narrow palate and relatively little facial expression). The majority of key features characteristic for Bohring-Opitz syndrome were absent in our patients (eg, the typical posture of arms, intrauterine growth retardation, microcephaly, trigonocephaly, typical facial gestalt with nevus flammeus of the forehead and exophthalmos). Therefore we emphasize that BRPS syndrome, caused by ASXL3 loss-of-function variants, is a clinically distinct intellectual disability syndrome with a recognizable phenotype distinguishable from that of Bohring-Opitz syndrome.
Type de document :
Article dans une revue
European Journal of Human Genetics, Nature Publishing Group, 2017, 25 (2), pp.183-191. 〈https://www.nature.com/npg_/contact/offices.html〉. 〈10.1038/ejhg.2016.165〉
Liste complète des métadonnées

Littérature citée [24 références]  Voir  Masquer  Télécharger

https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01550212
Contributeur : Gad - Université de Bourgogne <>
Soumis le : mardi 20 mars 2018 - 17:43:28
Dernière modification le : dimanche 15 avril 2018 - 20:40:02

Fichier

ejhg2016165a.pdf
Publication financée par une institution

Identifiants

Collections

Citation

Alma Kuechler, Johanna Czeschik,, Elisabeth Graf, Ute Grasshoff, Ulrike Hueffmeier,, et al.. Bainbridge-Ropers syndrome caused by loss-of-function variants in ASXL3: a recognizable condition. European Journal of Human Genetics, Nature Publishing Group, 2017, 25 (2), pp.183-191. 〈https://www.nature.com/npg_/contact/offices.html〉. 〈10.1038/ejhg.2016.165〉. 〈hal-01550212〉

Partager

Métriques

Consultations de la notice

130

Téléchargements de fichiers

21