Expanding the phenotype of Wiedemann-Steiner syndrome: Craniovertebral junction anomalies

Sara Giangiobbe, Stefano Giuseppe Caraffi, Ivan Ivanovski, Ilenia Maini, Marzia Pollazzon, Simonetta Rosato, Gabriele Trimarchi, Anna Lauriello, Maria Marinelli, Davide Nicoli, Chiara Baldo, Steven Laurie, Josue Flores-Daboub, Aldesia Provenzano, Elena Andreucci, Francesca Peluso, Renata Rizzo, Helen Stewart, Katherine Lachlan, Allan BayatManuela Napoli, Giorgia Carboni, Janice Baker, Alyssa Mendel, Gianluca Piatelli, Chiara Pantaleoni, Teresa Mattina, Paolo Prontera, Nancy J Mendelsohn, Sabrina Giglio, Orsetta Zuffardi, Livia Garavelli

Publikation: Bidrag til tidsskriftArtikelForskningpeer review


Wiedemann-Steiner syndrome (WDSTS) is a rare autosomal dominant condition caused by heterozygous loss of function variants in the KMT2A (MLL) gene, encoding a lysine N-methyltransferase that mediates a histone methylation pattern specific for epigenetic transcriptional activation. WDSTS is characterized by a distinctive facial phenotype, hypertrichosis, short stature, developmental delay, intellectual disability, congenital malformations, and skeletal anomalies. Recently, a few patients have been reported having abnormal skeletal development of the cervical spine. Here we describe 11 such individuals, all with KMT2A de novo loss-of-function variants: 10 showed craniovertebral junction anomalies, while an 11th patient had a cervical abnormality in C7. By evaluating clinical and diagnostic imaging data we characterized these anomalies, which consist primarily of fused cervical vertebrae, C1 and C2 abnormalities, small foramen magnum and Chiari malformation type I. Craniovertebral anomalies in WDSTS patients have been largely disregarded so far, but the increasing number of reports suggests that they may be an intrinsic feature of this syndrome. Specific investigation strategies should be considered for early identification and prevention of craniovertebral junction complications in WDSTS patients.

Sider (fra-til)2877-2886
Antal sider10
TidsskriftAmerican Journal of Medical Genetics, Part A
Udgave nummer12
StatusUdgivet - dec. 2020

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