The chromosome 9q subtelomere deletion syndrome§


  • Douglas R. Stewart,

    Corresponding author
    • National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive, Bldg. 49, Room 4A62, Bethesda, MD 20892.
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    • Douglas R. Stewart, M.D. is an internist who developed an interest in the 9qSTDS during his clinical genetics fellowship at the Children's Hospital of Philadelphia. He is now at the National Institutes of Health in Bethesda, MD, where he has a lab and clinic investigating neurofibromatosis type 1.

  • Tjitske Kleefstra

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    • Tjitske Kleefstra, M.D., Ph.D. is a clinical geneticist working at the Department of Human Genetics, Radbound University Nijmegen Medical Centre, The Netherlands, with a particular interest in the field of mental retardation.

  • This article is a US Government work and, as such, is in the public domain in the United States of America.

  • The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government.

  • §

    How to cite this article: Stewart DR, Kleefstra T. 2007. The chromosome 9q subtelomere deletion syndrome. Am J Med Genet Part C Semin Med Genet 145C:383–392.


The chromosome 9q subtelomere deletion syndrome (9qSTDS) is among the first and most common clinically recognizable syndromes to arise from widespread testing by fluorescent in situ hybridization (FISH) of subtelomere deletions. There are about 50 reported cases worldwide. Affected individuals invariably have severe hypotonia with speech and gross motor delay. The facial gestalt is distinct and features absolute or relative micro- or brachycephaly, hypertelorism, synophrys, and/or arched eyebrows, mid-face hypoplasia, a short nose with upturned nares, a protruding tongue with everted lower lip and down-turned corners of the mouth. Approximately half of affected individuals have congenital heart defects (primarily ASD or VSD). A significant minority have epilepsy and/or behavioral and sleep disturbances. A variety of other major and minor eye, ear, genital, and limb anomalies have been reported. Most patients have sub-microscopic deletions of the subtelomere region of chromosome 9q34.3 that range from <400 kb to >3 Mb. The 9qSTDS is caused by haplo-insufficiency of EHMT1, a gene whose protein product (Eu-HMTase1) is a histone H3 Lys 9 (H3-K9) methyltransferase. This was established by identification of three patients with features of the syndrome and either mutations or a balanced translocation in EHMT1. H3-K9 histone methylation is restricted to the euchromatin of mammals and functions to silence individual genes. Deletion size does not correlate with the severity of the 9qSTDS since patients with mutations in EHMT1 are as severely affected as those with submicroscopic deletions. Patients clinically suspected of having the 9qSTDS but with normal subtelomere deletion testing by FISH or MLPA should be considered for detailed 9q MLPA analysis and/or sequencing of EHMT1. EHMT1 is another example in the growing list of genes responsible for brain development that appear to play a role in chromatin remodeling. Published 2007 Wiley-Liss, Inc.