Expanding the clinical phenotype of the ultra-rare Skraban-Deardorff syndrome: Two novel individuals with WDR26 loss-of-function variants and a literature review.

Trajkova S

Pavinato L(1)(2), Trajkova S(1), Grosso E(3), Giorgio E(4), Bruselles A(5), Radio FC(6), Pippucci T(7), Dimartino P(8), Tartaglia M(6), Petlichkovski A(9), De Rubeis S(10)(11)(12)(13), Buxbaum J(10)(11)(12)(13)(14)(15), Ferrero GB(16), Keller R(17), Brusco A(1)(3).
Author information:
(1)Department of Medical Sciences, University of Turin, Turin, Italy.
(2)Institute of Human Genetics and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
(3)Medical Genetics Unit, Città della Salute e della Scienza University Hospital, Turin, Italy.
(4)Department of Molecular Medicine, University of Pavia, Pavia, Italy.
(5)Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
(6)Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.
(7)Medical Genetics Unit, Polyclinic Sant'Orsola-Malpighi University Hospital, Bologna, Italy.
(8)Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
(9)Institute for Immunobiology and Human Genetics, Faculty of Medicine, University "Sv. Kiril I Metodij", Skopje, Macedonia.
(10)Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
(11)Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
(12)The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
(13)Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
(14)Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
(15)Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
(16)Department of Clinical and Biological Sciences, School of Medicine, University of Turin, Orbassano, Torino, Italy.
(17)Adult autism center, Mental Health Department, Local Health Unit ASL Città di Torino, Turin, Italy.

https://dx.doi.org/10.1002/ajmg.a.62157

De novo variants in the WDR26 gene leading to haploinsufficiency have recently been associated with Skraban-Deardorff syndrome. This condition is an ultra-rare autosomal dominant neurodevelopmental disorder characterized by a broad range of clinical signs, including intellectual disability (ID), developmental delay (DD), seizures, abnormal facial features, feeding difficulties, and minor skeletal anomalies. Currently, 18 cases have been reported in the literature and for only 15 of them a clinical description is available. Here, we describe a child with Skraban-Deardorff syndrome associated with the WDR26 pathogenic de novo variant NM_025160.6:c.69dupC, p.(Gly24ArgfsTer48), and an adult associated with the pathogenic de novo variant c.1076G > A, p.(Trp359Ter). The adult patient was a 29-year-old female with detailed information on clinical history and pharmacological treatments since birth, providing an opportunity to map disease progression and patient management. By comparing our cases with published reports of Skraban-Deardorff syndrome, we provide a genetic and clinical summary of this ultrarare condition, describe the clinical management from childhood to adult age, and further expand on the clinical phenotype.