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Schinzel–Giedion syndrome: a novel case, review and revised diagnostic criteria

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Abstract

Schinzel–Giedion syndrome (SGS) is a rare autosomal dominant inheritance disorder. Heterozygous de novo mutations in the SETBP1 gene have been identified as the genetic cause of SGS. Here, we report a novel case with the syndrome with a novel insertion mutation in SETBP1. We also present a review of SGS cases, and first revise diagnostic criteria of SGS based on clinical findings and/or SETBP1 mutation worldwide. A revised diagnostic criteria and typing of SGS can be determined. Type I (complex and classic type) SGS patients present a development delay and typical facial features (prominent forehead, midface retraction, and short and upturned nose) associated with hydronephrosis or two of the characteristic skeletal anomalies (a sclerotic skull base, wide occipital synchondrosis, increased cortical density or thickness, and broad ribs). Type II (middle type) patients show development delay and the distinctive facial phenotype (midface retraction, short and upturned nose), lacking both hydronephrosis and typical skeletal abnormalities, with existence of SETBP1 mutation. Type III (simple type) patients with SETBP1 alteration show their major symptom is development delay, in which expressive language delay is the most striking feature. Central nervous system involvement with development delay in which expressive language delay is much more obviously affected is the most prominent feature of SGS. There is another indication that severity of phenotype of SGS may be inversely correlated with degree of SETBP1 alteration, besides gain-of-function or dominant-negative effects in SETBP1 alteration causing SGS.

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Acknowledgements

We thank the patient and his families, and clinicians who collaborated in this study. Our work is supported by the section of scientific research, Science and Technology Department of Guizhou Province in China (20147122) and by The Science and Technology Plan Project of Guiyang, China (2014100142).

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  1. Wei-Liang Liu, Zhi-Xu He and Fang Li contributed equally to this work.

Authors and Affiliations

  1. Department of Developmental Pediatrics, Affiliated Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of China

    Wei-Liang Liu & Hong-Wei Ma

  2. Department of Pediatrics, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, People’s Republic of China

    Wei-Liang Liu, Zhi-Xu He & Rong Ai

  3. Department of Ophthalmology, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, People’s Republic of China

    Fang Li

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  1. Wei-Liang Liu
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Correspondence to Wei-Liang Liu, Zhi-Xu He or Hong-Wei Ma.

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Corresponding editor: Arun Kumar

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Liu, WL., He, ZX., Li, F. et al. Schinzel–Giedion syndrome: a novel case, review and revised diagnostic criteria. J Genet 97, 35–46 (2018). https://doi.org/10.1007/s12041-017-0877-5

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