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Sections Genetics of Rubinstein-Taybi Syndrome
Overview
Presentation
DDx
Workup
Treatment
Medication
Follow-up
Media Gallery
References

Presentation

Physical

Patients show multiple congenital anomalies, including intellectual disabilities, growth deficiency (postnatal), microcephaly, broad thumbs and first toes, and dysmorphic facial features. Patients have a striking facial appearance, characterized by highly arched eyebrows, long eyelashes, abnormally slanting palpebral fissures, broad nasal bridge, beaked nose, and mandibular abnormalities, including mild micrognathia.^{[12, 13, 3]}

Selected physical findings

Facial abnormalities

These include the following:

Abnormal maxilla with narrow palate
Prominent beaked nose
Down-slanting palpebral fissures
Low-set and/or malformed ears
Strabismus
Large anterior fontanel
Microcephaly
Malpositioned or crowded teeth, high palate, short upper lip, and protuberant lower lip are also seen

Digit abnormalities

These include the following:

Broad great toes
Broad thumbs with radial angulation
Broadness of other fingers
Persistent fetal finger pads
Syndactyly and polydactyly

Abnormalities of growth and development

These include the following:

Mental retardation with intelligence quotient (IQ) of 30-79 (average 51) - More than 50% of patients have an IQ of less than 50
Speech difficulty
Hypotonia
Electroencephalographic abnormalities (even in the absence of seizures)
Growth retardation (postnatal-onset growth deficiency; Rubinstein-Taybi syndrome [RSTS]–specific charts are available) - Average male height: 153 cm; average female height: 147 cm
Feeding problems - Gastroesophageal reflux

Skeletal abnormalities

These include the following:

Retarded osseous maturation
Vertebral and sternal abnormalities
Patellar dislocation

Cardiac anomalies

These include the following:

Ventricular septal defect (VSD) and patent ductus arteriosus (PDA) are most common
Atrial septal defect (ASD), coarctation of the aorta, pulmonic stenosis, and bicuspid aortic valve

Other symptoms and findings

These include the following:

Cryptorchidism (very common in males)
Hirsutism
Keloid formation
Cardiac arrhythmias
Laryngeal wall collapsibility
Sleep and anesthesia problems

In a study by Ajmone et al of 23 patients with RSTS, brain magnetic resonance imaging (MRI) revealed that 73.6% of the cohort had dysmorphia of the corpus callosum, with or without the presence of other anomalies, such as minor dysmorphia of the cerebellar vermis and hyperintensity of the posterior periventricular white matter. In addition, whole-spine MRI scans indicated a greater tendency for patients with RSTS to have a low-lying conus medullaris without thickening of the filum terminale.^[14]

Differential Diagnoses

Rubinstein JH, Taybi H. Broad thumbs and toes and facial abnormalities. Am J Dis Child. 1963. 105:588-608.
Milani D, Manzoni FM, Pezzani L, et al. Rubinstein-Taybi syndrome: clinical features, genetic basis, diagnosis, and management. Ital J Pediatr. 2015 Jan 20. 41:4. [QxMD MEDLINE Link]. [Full Text].
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].
Solomon BD, Bodian DL, Khromykh A, et al. Expanding the phenotypic spectrum in EP300-related Rubinstein-Taybi syndrome. Am J Med Genet A. 2015 May. 167A (5):1111-6. [QxMD MEDLINE Link].
Rubinstein-Taybi Syndrome 2; RSTS2. OMIM. Available at http://www.omim.org/entry/613684. May 27, 2016; Accessed: Sep 8, 2016.
Ajmone PF, Avignone S, Gervasini C, et al. Rubinstein-Taybi syndrome: new neuroradiological and neuropsychiatric insights from a multidisciplinary approach. Am J Med Genet B Neuropsychiatr Genet. 2018 Jun. 177 (4):406-15. [QxMD MEDLINE Link].
Lee JS, Byun CK, Kim H, et al. Clinical and mutational spectrum in Korean patients with Rubinstein-Taybi syndrome: the spectrum of brain MRI abnormalities. Brain Dev. 2015 Apr. 37 (4):402-8. [QxMD MEDLINE Link].
Balci S, Ergun MA, Yuksel-Konuk EB, Bartsch O. Rubinstein-Taybi syndrome with normal FISH result and CREBBP gene analysis: a case report. Turk J Pediatr. 2008 May-Jun. 50(3):265-8. [QxMD MEDLINE Link].
Stevens CA, Pagon RA, Adam MP, et al. Rubinstein-Taybi Syndrome. 1993. [QxMD MEDLINE Link]. [Full Text].
Boot MV, van Belzen MJ, Overbeek LI, et al. Benign and malignant tumors in Rubinstein-Taybi syndrome. Am J Med Genet A. 2018 Mar. 176 (3):597-608. [QxMD MEDLINE Link]. [Full Text].
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].
Herriot R, Miedzybrodzka Z. Antibody deficiency in Rubinstein-Taybi syndrome. Clin Genet. 2016 Mar. 89 (3):355-8. [QxMD MEDLINE Link].

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.

Sections Genetics of Rubinstein-Taybi Syndrome
Overview
Presentation
DDx
Workup
Treatment
Medication
Follow-up
Media Gallery
References

Genetics of Rubinstein-Taybi Syndrome Clinical Presentation

Physical

Selected physical findings

References

Tables

Contributor Information and Disclosures

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