UBE2A deficiency syndrome: Mild to severe intellectual disability accompanied by seizures, absent speech, urogenital, and skin anomalies in male patients

Authors

  • Nicole de Leeuw,

    1. Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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  • Saskia Bulk,

    1. Department of Medical Genetics, University Medical Center, Utrecht, The Netherlands
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  • Andrew Green,

    1. National Centre for Medical Genetics, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland
    2. UCD School of Medicine and Medical Science, Dublin, Ireland
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  • Lane Jaeckle-Santos,

    1. McDermott Center for Human Growth and Development, Department of Internal Medicine, The University of Texas Southwestern Medical School, Dallas, Texas
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  • Linda A. Baker,

    1. Department of Urology, The University of Texas Southwestern Medical School, Dallas, Texas
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  • Andrew R. Zinn,

    1. McDermott Center for Human Growth and Development, Department of Internal Medicine, The University of Texas Southwestern Medical School, Dallas, Texas
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  • Tjitske Kleefstra,

    1. Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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  • Jasper J. van der Smagt,

    1. Department of Medical Genetics, University Medical Center, Utrecht, The Netherlands
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  • Angela Maria Vianne Morgante,

    1. Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil
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  • Bert B.A. de Vries,

    1. Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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  • Hans van Bokhoven,

    1. Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    2. Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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  • Arjan P.M. de Brouwer

    Corresponding author
    1. Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    • Department of Human Genetics, 855, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
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  • How to Cite this Article: de Leeuw N, Bulk S, Green A, Jaeckle-Santos L, Baker LA, Zinn AR, Kleefstra T, van der Smagt JJ, Vianne Morgante AM, de Vries BBA, van Bokhoven H, de Brouwer APM. 2010. UBE2A deficiency syndrome: Mild to severe intellectual disability accompanied by seizures, absent speech, urogenital, and skin anomalies in male patients. Am J Med Genet Part A 152A:3084–3090.

Abstract

We describe three patients with a comparable deletion encompassing SLC25A43, SLC25A5, CXorf56, UBE2A, NKRF, and two non-coding RNA genes, U1 and LOC100303728. Moderate to severe intellectual disability (ID), psychomotor retardation, severely impaired/absent speech, seizures, and urogenital anomalies were present in all three patients. Facial dysmorphisms include ocular hypertelorism, synophrys, and a depressed nasal bridge. These clinical features overlap with those described in two patients from a family with a similar deletion at Xq24 that also includes UBE2A, and in several patients of Brazilian and Polish families with point mutations in UBE2A. Notably, all five patients with an Xq24 deletion have ventricular septal defects that are not present in patients with a point mutation, which might be attributed to the deletion of SLC25A5. Taken together, the UBE2A deficiency syndrome in male patients with a mutation in or a deletion of UBE2A is characterized by ID, absent speech, seizures, urogenital anomalies, frequently including a small penis, and skin abnormalities, which include generalized hirsutism, low posterior hairline, myxedematous appearance, widely spaced nipples, and hair whorls. Facial dysmorphisms include a wide face, a depressed nasal bridge, a large mouth with downturned corners, thin vermilion, and a short, broad neck. © 2010 Wiley-Liss, Inc.

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