Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

A nationwide survey of Schaaf-Yang syndrome in Japan


Schaaf-Yang syndrome (SYS) is a congenital disorder characterized by developmental delay, autism spectrum disorder and congenital joint contractures. In this study, a nationwide epidemiological questionnaire-based survey of SYS in the Japanese population was conducted to establish patient numbers, clinical features and genetic information. In the primary survey, we investigated the number of SYS patients. In the secondary survey, we obtained and analyzed detailed clinical and genetic information of SYS patients. This survey collected information on 25 genetically-confirmed patients. The major clinical symptoms included neonatal hypotonia (96% of the patients), poor suck in infancy (82%), developmental delay (100%) and joint contractures (83%). Other main symptoms and findings included characteristic facial features (100%), small hands (92%), eye abnormalities (92%) and short stature (79%). Based on the information collected on activities of daily living, 71% of patients were unable to walk, while 67%, 71%, and 81% of patients required full assistance with eating, toileting and bathing, respectively. Regarding inheritability, the genetic analysis of 21 patients revealed that 14 (67%) carried de novo truncating variants in the melanoma antigen L2 (MAGEL2) gene and seven (33%) had inherited truncating variants from their fathers who were carriers. This survey revealed the clinical and genetic features in Japanese SYS patients. The majority of SYS patients required assistance in many aspects of daily living, and there were a certain number of carriers of the imprinting disorder.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1


  1. Schaaf CP, Gonzalez-Garay ML, Xia F, Potocki L, Gripp KW, Zhang B, et al. Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism. Nat Genet. 2013;45:1405–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. McCarthy J, Lupo PJ, Kovar E, Rech M, Bostwick B, Scott D, et al. Schaaf-Yang syndrome overview: report of 78 individuals. Am J Med Genet A. 2018;176:2564–74.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Schaaf CP, Marbach F. Schaaf-Yang syndrome. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Gripp KW, et al. editors. GeneReviews®. Seattle: University of Washington; 1993.

  4. Cassidy SB, Schwartz S, Miller JL, Driscoll DJ. Prader-Willi syndrome. Genet Med. 2012;14:10–26.

    Article  PubMed  CAS  Google Scholar 

  5. Patak J, Gilfert J, Byler M, Neerukonda V, Thiffault I, Cross L, et al. MAGEL2-related disorders: a study and case series. Clin Genet. 2019;96:493–505.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Negishi Y, Ieda D, Hori I, Nozaki Y, Yamagata T, Komaki H, et al. Schaaf-Yang syndrome shows a Prader-Willi syndrome-like phenotype during infancy. Orphanet J Rare Dis. 2019;14:277.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Hao YH, Doyle JM, Ramanathan S, Gomez TS, Jia D, Xu M, et al. Regulation of WASH-dependent actin polymerization and protein trafficking by ubiquitination. Cell. 2013;152:1051–64.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Tacer KF, Potts PR. Cellular and disease functions of the Prader-Willi Syndrome gene MAGEL2. Biochem J. 2017;474:2177–90.

    Article  PubMed  CAS  Google Scholar 

  9. Saitoh S. Endosomal recycling defects and neurodevelopmental disorders. Cells. 2022;11:148.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Marbach F, Elgizouli M, Rech M, Beygo J, Erger F, Velmans C, et al. The adult phenotype of Schaaf-Yang syndrome. Orphanet J Rare Dis. 2020;15:294.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Adachi T, Kawamura K, Furusawa Y, Nishizaki Y, Imanishi N, Umehara S, et al. Japan’s initiative on rare and undiagnosed diseases (IRUD): towards an end to the diagnostic odyssey. Eur J Hum Genet. 2017;25:1025–8.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Tsuboi T. Epidemiology of febrile and afebrile convulsions in children in Japan. Neurology. 1984;34:175–81.

    Article  PubMed  CAS  Google Scholar 

  13. Hoshino A, Saitoh M, Oka A, Okumura A, Kubota M, Saito Y, et al. Epidemiology of acute encephalopathy in Japan, with emphasis on the association of viruses and syndromes. Brain Dev. 2012;34:337–43.

    Article  PubMed  Google Scholar 

Download references


We deeply thank all those who participated in this survey.


This work was supported by MHLW Research on rare and intractable diseases Program Grant Number JPMH20FC1003 (YN, KK, KT, KM, TN, and?SS).

Author information

Authors and Affiliations



YN analyzed and interpreted data, and wrote the manuscript. KK, KT, KM, TN, and KN analyzed and interpreted data. SS initiated the project, analyzed the data and wrote the manuscript. All authors commented on and edited the final manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Shinji Saitoh.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Negishi, Y., Kurosawa, K., Takano, K. et al. A nationwide survey of Schaaf-Yang syndrome in Japan. J Hum Genet 67, 735–738 (2022).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


Quick links