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.
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Rubinstein JH, Taybi H. Broad thumbs and toes and facial abnormalities. Am J Dis Child. 1963;105:588–608.
Hennekam RC. Rubinstein-Taybi syndrome. Eur J Hum Genet. 2006;14:981–5.
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.
Stevens CA, Pouncey J, Knowles D. Adults with Rubinstein-Taybi syndrome. Am J Med Genet A. 2011;155A:1680–4.
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.
Wiley S, Swayne S, Rubinstein JH, Lanphear NE, Stevens CA. Rubinstein-Taybi syndrome medical guidelines. Am J Med Genet A. 2003;119A:101–10.
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.
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.
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.
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.
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.
Cotsirilos P, Taylor JC, Matalon R. Dominant inheritance of a syndrome similar to Rubinstein-Taybi. Am J Med Genet. 1987;26:85–93.
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.
Levitas AS, Reid CS. Rubinstein-Taybi syndrome and psychiatric disorders. J Intellect Disabil Res. 1998;42:284–92.
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.
Nayak RB, Lakshmappa A, Patil NM, Chate SS, Somashekar L. Rubinstein-taybi syndrome with psychosis. Indian J Psychol Med. 2012;34:184–6.
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.
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.
Groves L, Oliver C, Moss J. Behaviour across the lifespan in Cornelia de Lange syndrome. Curr Opin Psychiatry. 2021;34:112–7.
Stevens CA, Carey JC, Blackburn BL. Rubinstein-Taybi syndrome: a natural history study. Am J Med Genet. 1990;6:30–37.
World Health Organization. The top 10 causes of death. 2020. https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death.
Marion RW, Garcia DM, Karasik JB. Apparent dominant transmission of the Rubinstein-Taybi syndrome. Am J Med Genet. 1993;46:284–7.
Siraganian PA, Rubinstein JH, Miller RW. Keloids and neoplasms in the Rubinstein-Taybi syndrome. Med Pediatr Oncol. 1989;17:485–91.
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.
Fischer S, Bäzner H, Henkes H. Cervical artery dissection in a young patient with Rubinstein-Taybi syndrome. Clin Neuroradiol. 2013;23:41–4.
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.
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.
Herriot R, Miedzybrodzka Z. Antibody deficiency in Rubinstein-Taybi syndrome. Clin Genet. 2016;89:355–8.
Miller RW, Rubinstein JH. Tumors in Rubinstein-Taybi syndrome. Am J Med Genet. 1995;56:112–5.
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.
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.
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].
The authors declare no competing interests.
This investigation was performed in accordance with the Declaration of Helsinki. Reported information was provided voluntarily by all participants filing in the questionnaire.
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.
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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). https://doi.org/10.1038/s41431-022-01097-8
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