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.

The natural history of adults with Rubinstein-Taybi syndrome: a families-reported experience


The existing knowledge about morbidity in adults with Rubinstein-Taybi syndrome (RTS) is limited and detailed data on their natural history and response to management are needed for optimal care in later life. We formed an international, multidisciplinary working group that developed an accessible questionnaire including key issues about adults with RTS and disseminated this to all known RTS support groups via social media. We report the observations from a cohort of 87 adult individuals of whom 43 had a molecularly confirmed diagnosis. The adult natural history of RTS is defined by prevalent behavioural/psychiatric problems (83%), gastrointestinal problems (73%) that are represented mainly by constipation; and sleep problems (62%) that manifest in a consistent pattern of sleep apnoea, difficulty staying asleep and an increased need for sleep. Furthermore, over than half of the RTS individuals (65%) had skin and adnexa-related problems. Half of the individuals receive multidisciplinary follow-up and required surgery at least once, and most frequently more than once, during adulthood. Our data confirm that adults with RTS enjoy both social and occupational possibilities, show a variegated experience of everyday life but experience a significant morbidity and ongoing medical issues which do not appear to be as coordinated and multidisciplinary managed as in paediatric patients. We highlight the need for optimal care in a multidisciplinary setting including the pivotal role of specialists for adult care.

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: Adult RTS reported everyday life.
Fig. 2: Summary of adult RTS morbidity by body system.
Fig. 3: Pattern of RTS behavioural or psychiatric problems.
Fig. 4: Medical follow-up and surgery details.

Data availability

All data generated or analysed during this study are included in this published article.


  1. Rubinstein JH, Taybi H. Broad thumbs and toes and facial abnormalities. Am J Dis Child. 1963;105:588–608.

    CAS  Article  Google Scholar 

  2. Hennekam RC. Rubinstein-Taybi syndrome. Eur J Hum Genet. 2006;14:981–5.

    CAS  Article  Google Scholar 

  3. Hennekam RC, Van Den Boogaard MJ, Sibbles BJ, Van Spijker HG. Rubinstein-Taybi syndrome in the Netherlands. Am J Med Genet. 1990;6:17–29.

    CAS  Google Scholar 

  4. Stevens CA, Pouncey J, Knowles D. Adults with Rubinstein-Taybi syndrome. Am J Med Genet A. 2011;155A:1680–4.

    Article  Google Scholar 

  5. van Genderen MM, Kinds GF, Riemslag FC, Hennekam RC. Ocular features in Rubinstein-Taybi syndrome: investigation of 24 patients and review of the literature. Br J Ophthalmol. 2000;84:1177–84.

    Article  Google Scholar 

  6. Wiley S, Swayne S, Rubinstein JH, Lanphear NE, Stevens CA. Rubinstein-Taybi syndrome medical guidelines. Am J Med Genet A. 2003;119A:101–10.

    Article  Google Scholar 

  7. Yagihashi T, Kosaki K, Okamoto N, Mizuno S, Kurosawa K, Takahashi T, et al. Age-dependent change in behavioral feature in Rubinstein-Taybi syndrome. Congenit Anom. 2012;52:82–6.

    Article  Google Scholar 

  8. Milani D, Manzoni FM, Pezzani L, Ajmone P, Gervasini C, Menni F, et al. Rubinstein-Taybi syndrome: clinical features, genetic basis, diagnosis, and management. Ital J Pediatr. 2015;41:4–12.

    Article  Google Scholar 

  9. Boot MV, van Belzen MJ, Overbeek LI, Hijmering N, Mendeville M, Waisfisz Q, et al. Benign and malignant tumors in Rubinstein-Taybi syndrome. Am J Med Genet A. 2018;176:597–608.

    CAS  Article  Google Scholar 

  10. Yamamoto T, Kurosawa K, Masuno M, Okuzumi S, Kondo S, Miyama S, et al. Congenital anomaly of cervical vertebrae is a major complication of Rubinstein-Taybi syndrome. Am J Med Genet A. 2005;135:130–3.

    Article  Google Scholar 

  11. Utumi ER, Pedron IG, Zambon CE, Neto NP, Rocha AC. Rare occurrence of myositis ossificans traumatica in a patient with Rubinstein-Taybi syndrome. J Oral Maxillofac Surg. 2010;68:2616–22.

    Article  Google Scholar 

  12. Cotsirilos P, Taylor JC, Matalon R. Dominant inheritance of a syndrome similar to Rubinstein-Taybi. Am J Med Genet. 1987;26:85–93.

    CAS  Article  Google Scholar 

  13. Hennekam RC, Baselier AC, Beyaert E, Bos A, Blok JB, Jansma HB, et al. Psychological and speech studies in Rubinstein-Taybi syndrome. Am J Ment Retard. 1992;96:645–60.

    CAS  PubMed  Google Scholar 

  14. Levitas AS, Reid CS. Rubinstein-Taybi syndrome and psychiatric disorders. J Intellect Disabil Res. 1998;42:284–92.

    Article  Google Scholar 

  15. Hellings JA, Hossain S, Martin JK, Baratang RR. Psychopathology, GABA, and the Rubinstein-Taybi syndrome: a review and case study. Am J Med Genet. 2002;114:190–5.

    Article  Google Scholar 

  16. Nayak RB, Lakshmappa A, Patil NM, Chate SS, Somashekar L. Rubinstein-taybi syndrome with psychosis. Indian J Psychol Med. 2012;34:184–6.

    Article  Google Scholar 

  17. Waite J, Moss J, Beck SR, Richards C, Nelson L, Arron K, et al. Repetitive behavior in Rubinstein-Taybi syndrome: parallels with autism spectrum phenomenology. J Autism Dev Disord. 2015;45:1238–53.

    Article  Google Scholar 

  18. Chan AJS, Cytrynbaum C, Hoang N, Ambrozewicz PM, Weksberg R, Drmic I, et al. Expanding the neurodevelopmental phenotypes of individuals with de novo KMT2A variants. NPJ Genom Med. 2019;4:9–18.

    Article  Google Scholar 

  19. Groves L, Oliver C, Moss J. Behaviour across the lifespan in Cornelia de Lange syndrome. Curr Opin Psychiatry. 2021;34:112–7.

    Article  Google Scholar 

  20. Stevens CA, Carey JC, Blackburn BL. Rubinstein-Taybi syndrome: a natural history study. Am J Med Genet. 1990;6:30–37.

    CAS  Google Scholar 

  21. World Health Organization. The top 10 causes of death. 2020.

  22. Marion RW, Garcia DM, Karasik JB. Apparent dominant transmission of the Rubinstein-Taybi syndrome. Am J Med Genet. 1993;46:284–7.

    CAS  Article  Google Scholar 

  23. Siraganian PA, Rubinstein JH, Miller RW. Keloids and neoplasms in the Rubinstein-Taybi syndrome. Med Pediatr Oncol. 1989;17:485–91.

    CAS  Article  Google Scholar 

  24. Balci S, Ali Ergün M, Lechno S, Bartsch O. Rubinstein-Taybi syndrome in first cousins with different de novo mutations. Am J Med Genet A. 2010;152A:1036–8.

    Article  Google Scholar 

  25. Fischer S, Bäzner H, Henkes H. Cervical artery dissection in a young patient with Rubinstein-Taybi syndrome. Clin Neuroradiol. 2013;23:41–4.

    CAS  Article  Google Scholar 

  26. Kim CJ, Nam JH, Chung HY, Kook JH, Kim SY, Woo YJ. Kimura disease in a patient with Rubinstein-Taybi syndrome. Pediatr Int. 2004;46:609–11.

    Article  Google Scholar 

  27. Naimi DR, Munoz J, Rubinstein J, Hostoffer RW Jr. Rubinstein-Taybi syndrome: an immune deficiency as a cause for recurrent infections. Allergy Asthma Proc. 2006;27:281–4.

    Article  Google Scholar 

  28. Herriot R, Miedzybrodzka Z. Antibody deficiency in Rubinstein-Taybi syndrome. Clin Genet. 2016;89:355–8.

    CAS  Article  Google Scholar 

  29. Miller RW, Rubinstein JH. Tumors in Rubinstein-Taybi syndrome. Am J Med Genet. 1995;56:112–5.

    CAS  Article  Google Scholar 

  30. Bayle P, Bazex J, Lamant L, Lauque D, Durieu C, Albes B. Multiple perforating and non perforating pilomatricomas in a patient with Churg-Strauss syndrome and Rubinstein-Taybi syndrome. J Eur Acad Dermatol Venereol. 2004;18:607–10.

    CAS  Article  Google Scholar 

  31. Papathemeli D, Schulzendorff N, Kohlhase J, Göppner D, Franke I, Gollnick H. Pilomatricomas in Rubinstein-Taybi syndrome. J Dtsch Dermatol Ges. 2015;13:240–2.

    PubMed  Google Scholar 

Download references


We thank all the RTS individuals and their families for their time and dedication in providing us with this invaluable information. This work has been generated within the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability (ERN-ITHACA) [EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/79516].

Author information

Authors and Affiliations



All authors acquired data and approved the final version of the manuscript. SH and SGM played an important role in interpreting the results. SD and RCMH conceived and designed the work that led to the submission, drafted and revised the manuscript.

Corresponding author

Correspondence to Sofia Douzgou.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethical approval

This investigation was performed in accordance with the Declaration of Helsinki. Reported information was provided voluntarily by all participants filing in the questionnaire.

Additional information

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

SD, SH, KV, DL, and RCMH are members of ERN-ITHACA.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Douzgou, S., Dell’Oro, J., Fonseca, C.R. et al. The natural history of adults with Rubinstein-Taybi syndrome: a families-reported experience. Eur J Hum Genet 30, 841–847 (2022).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links