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Journal Articles Clinical Genetics Year : 2018

Wiedemann-Steiner syndrome as a major cause of syndromic intellectual disability: A study of 33 French cases

1 Les Hôpitaux Universitaires de Strasbourg (HUS)
2 Laboratoire de Diagnostic Génétique [CHU Strasbourg]
3 CHU Trousseau [APHP]
4 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
5 LHEEA - Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique
6 UMR_S567 / UMR 8104 - Institut Cochin
7 IC UM3 (UMR 8104 / U1016) - Institut Cochin
8 Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier]
9 Service de Génétique [CHU Caen]
10 BIOTARGEN - Biologie, génétique et thérapies ostéoarticulaires et respiratoires
11 HCL - Hospices Civils de Lyon
12 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
13 GHICL - Groupe Hospitalier de l'Institut Catholique de Lille
14 Hôpital universitaire Robert Debré [Reims]
15 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
16 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
17 Service de génétique [Rouen]
18 CHU Marseille
19 CHU Pitié-Salpêtrière [AP-HP]
20 Service de génétique médicale - Unité de génétique clinique [Nantes]
21 CHU Bordeaux
22 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
23 IMSIA - UMR 9219 - Institut des Sciences de la mécanique et Applications industrielles
24 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)
25 Unité de génétique médicale et oncogénétique [CHU Amiens Picardie]
26 Service de génétique clinique [Rennes]
27 Département de génétique médicale [Hôpital de la Timone - APHM]
28 GAD - Génétique des Anomalies du Développement
29 GMFC - Génétique du cancer et des maladies neuropsychiatriques
30 Hôpital Saint Vincent de Paul de Lille
31 Pôle de Biologie Pathologie Génétique [CHU Lille]
32 IMPMC - Institut de minéralogie et de physique des milieux condensés
A. Afenjar
  • Function : Author
M. Grelet
  • Function : Author
D. Lacombe
  • Function : Author

Abstract

Wiedemann-Steiner syndrome (WSS) is a rare syndromic condition in which intellectual disability (ID) is associated with hypertrichosis cubiti, short stature, and characteristic facies. Following the identification of the causative gene (KMT2A) in 2012, only 31 cases of WSS have been described precisely in the literature. We report on 33 French individuals with a KMT2A mutation confirmed by targeted gene sequencing, high-throughput sequencing or exome sequencing. Patients' molecular and clinical features were recorded and compared with the literature data. On the molecular level, we found 29 novel mutations. We observed autosomal dominant transmission of WSS in 3 families and mosaicism in one family. Clinically, we observed a broad phenotypic spectrum with regard to ID (mild to severe), the facies (typical or not of WSS) and associated malformations (bone, cerebral, renal, cardiac and ophthalmological anomalies). Hypertrichosis cubiti that was supposed to be pathognomonic in the literature was found only in 61% of our cases. This is the largest series of WSS cases yet described to date. A majority of patients exhibited suggestive features, but others were less characteristic, only identified by molecular diagnosis. The prevalence of WSS was higher than expected in patients with ID, suggesting than KMT2A is a major gene in ID.
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Dates and versions

hal-02393652 , version 1 (04-12-2019)

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S. Baer, A. Afenjar, T. Smol, A. Piton, B. Gérard, et al.. Wiedemann-Steiner syndrome as a major cause of syndromic intellectual disability: A study of 33 French cases. Clinical Genetics, 2018, 94 (1), pp.141-152. ⟨10.1111/cge.13254⟩. ⟨hal-02393652⟩
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