Approach Considerations

The following tests are used in the diagnosis and monitoring of Rubinstein-Taybi syndrome (RSTS):

Microarray
Whole exome sequencing (WES)
Targeted sequencing of CBP and EP300
Electroencephalogram - Strongly consider even in the absence of seizures
Measurement of growth and plotting of parameters on published syndrome-specific growth charts ^[6]
Ophthalmologic examination
Hearing evaluation in newborn period and auditory brain stem evoked response testing
Regular dental evaluations
Echocardiogram
Monitoring for constipation
Monitoring for cryptorchidism in males
Specialty orthopedic assessment of thumbs and toes
Ongoing scoliosis evaluation
Monitoring for obstructive sleep apnea
Tethered cord evaluation - Neonatal ultrasonography of the spinal canal in all patients; magnetic resonance imaging (MRI) in symptomatic older patients

Imaging Studies

These include the following:

Ongoing scoliosis and spinal abnormalities evaluation
MRI if indicated by neuroexamination ^[15]
Echocardiogram or cardiology evaluation
Chest radiograph if pulmonary symptoms
Tethered cord evaluation - Neonatal ultrasonography of the spinal canal in all patients; MRI in symptomatic older patients

Other Tests

These include the following:

Chromosomal karyotype analysis
Fluorescence in situ hybridization (FISH) for chromosome band 16p13^[16]
Mutation analysis of the CBP gene
Electrocardiogram for cardiac investigation for congenital heart disease
Neurologic evaluation

Treatment & Management

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Lopez M, Garcia-Oguiza A, Armstrong J, et al. Rubinstein-Taybi 2 associated to novel EP300 mutations: deepening the clinical and genetic spectrum. BMC Med Genet. 2018 Mar 5. 19 (1):36. [QxMD MEDLINE Link]. [Full Text].
Negri G, Magini P, Milani D, et al. From Whole Gene Deletion to Point Mutations of EP300-Positive Rubinstein-Taybi Patients: New Insights into the Mutational Spectrum and Peculiar Clinical Hallmarks. Hum Mutat. 2016 Feb. 37 (2):175-83. [QxMD MEDLINE Link].
Rusconi D, Negri G, Colapietro P, et al. Characterization of 14 novel deletions underlying Rubinstein-Taybi syndrome: an update of the CREBBP deletion repertoire. Hum Genet. 2015 Jun. 134 (6):613-26. [QxMD MEDLINE Link].
[Guideline] Beets L, Rodríguez-Fonseca C, Hennekam RC. Growth charts for individuals with Rubinstein-Taybi syndrome. Am J Med Genet A. 2014 Sep. 164A (9):2300-9. [QxMD MEDLINE Link]. [Full Text].
Coupry I, Monnet L, Attia AA, et al. Analysis of CBP (CREBBP) gene deletions in Rubinstein-Taybi syndrome patients using real-time quantitative PCR. Hum Mutat. 2004. 23(3):278-284. [QxMD MEDLINE Link].
Roelfsema JH, White SJ, Ariyurek Y, et al. Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease. Am J Hum Genet. 2005. 76(4):572-580. [QxMD MEDLINE Link]. [Full Text].
Rubinstein-Taybi Syndrome. OMIM. Available at http://www.ncbi.nlm.nih.gov.
Enomoto Y, Yokoi T, Tsurusaki Y, et al. Divergent variant patterns among 19 patients with Rubinstein-Taybi syndrome uncovered by comprehensive genetic analysis including whole genome sequencing. Clin Genet. 2022 Mar. 101 (3):335-45. [QxMD MEDLINE Link].
[Guideline] Wiley S, Swayne S, Rubinstein JH, et al. Rubinstein-Taybi syndrome medical guidelines. Am J Med Genet A. 2003 Jun 1. 119(2):101-10. [QxMD MEDLINE Link].
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Rubinstein-Taybi Syndrome 2; RSTS2. OMIM. Available at http://www.omim.org/entry/613684. May 27, 2016; Accessed: Sep 8, 2016.
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Rusconi D, Negri G, Colapietro P, et al. Characterization of 14 novel deletions underlying Rubinstein-Taybi syndrome: an update of the CREBBP deletion repertoire. Hum Genet. 2015 Jun. 134 (6):613-26. [QxMD MEDLINE Link].
Negri G, Milani D, Colapietro P, et al. Clinical and molecular characterization of Rubinstein-Taybi syndrome patients carrying distinct novel mutations of the EP300 gene. Clin Genet. 2014 Jan 29. [QxMD MEDLINE Link].
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Media Gallery

Facial abnormalities (eg, hypoplastic maxilla, prominent beaked nose, antimongoloid palpebral fissures) and broad thumbs in a child with Rubinstein-Taybi syndrome (RSTS).
Prominent beaked nose, low-set ears, and broad thumbs in a child with Rubinstein-Taybi syndrome (RSTS).
Broad great toes in a child with Rubinstein-Taybi syndrome (RSTS).

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Author

Keith K Vaux, MD Professor of Medicine, Clinical Chief and Division Director, Division of Medical Genetics, Department of Medicine, University of California, San Diego, School of Medicine; Director, Rare Disease Program, Rady Children's Hospital San Diego and UC San Diego

Keith K Vaux, MD is a member of the following medical societies: American Academy of Pediatrics, Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Luis O Rohena, MD, PhD, FAAP, FACMG Deputy Chief, Department of Pediatrics, Chief, Medical Genetics, San Antonio Military Medical Center; Associate Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Associate Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD, PhD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Additional Contributors

Elaine H Zackai, MD Professor of Pediatrics, Professor of Obstetrics and Gynecology, Professor of Pediatrics in Human Genetics, University of Pennsylvania School of Medicine; Director, Clinical Genetics Center, University of Pennsylvania; Senior Physician and Director of Clinical Genetics, The Children's Hospital of Philadelphia

Elaine H Zackai, MD is a member of the following medical societies: American Cleft Palate-Craniofacial Association, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

David Flannery, MD, FAAP, FACMG Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia

David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Sulagna C Saitta, MD, PhD, to the original writing and development of this article.