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Dermatology > PEDIATRIC DISEASES
Rubinstein-Taybi Syndrome
Article Last Updated: Sep 20, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 10  
Author: Zeljko P Mijuskovic, MD, Consulting Staff, Department of Dermatology and Venereology, Military Medical Academy, Belgrade, Serbia
Zeljko P Mijuskovic is a member of the following medical societies: European Academy of Dermatology and Venereology and International Society of Dermatology
Coauthor(s):
Djordjije Karadaglic, MD, DSc, Professor, School of Medicine, University of Podgorica, Podgorica, Montenegro;
Ljubomir Stojanov, MD, PhD, Mother and Child Health Care Institute, Professor, Department of Metabolic and Genetic, University of Belgrade School of Medicine, Serbia
Editors: Mark A Crowe, MD, Assistant Clinical Instructor, Department of Medicine, Division of Dermatology, University of Washington School of Medicine; David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Director, Division of Dermatology, Scott and White Clinic; Director Dermatology Residency Training Program, Scott and White Clinic; Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School; Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University; William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
Author and Editor Disclosure
Synonyms and related keywords:
RSTS, broad thumb-hallux syndrome, mental retardation, broad big toes, prominent nose, growth retardation, feeding difficulties, congenital heart disease, developmental abnormalities
Background
In 1963, Rubinstein and Taybi first described Rubinstein-Taybi syndrome (RSTS) (Mendelian Inheritance in Man [MIM] #180849). RSTS is a well-delineated malformation syndrome characterized by facial abnormalities, broad thumbs, broad great toes, short stature, and mental retardation.
Pathophysiology
The locus of RSTS is located on band 16p13.3, which includes a gene encoding a binding protein for cyclic adenosine monophosphate–response element binding protein (CBP) (CREBBP or CBP gene) that is responsible for the phenotype of RSTS. Genetically based growth retardation and feeding difficulties are the main problems in early life; however, respiratory infections and complications from congenital heart disease are primary causes of morbidity and mortality in infancy.
Frequency
International
The prevalence of RSTS in the general population is approximately 1 case per 300,000 persons and is as high as 1 case per 10,000 live births. Cantani and Gagliesi reported that RSTS is not so rare and is present in approximately 1 in 600 patients seen in mental retardation clinics. Most cases of RSTS are sporadic, although it has been reported in monozygotic twins.
Mortality/Morbidity
The survival rate is good, with frequent reports of adult patients with RSTS. Respiratory infections and complications from congenital heart disease are primary causes of morbidity and mortality in infancy.
Race
RSTS has no racial predilection.
Sex
RSTS has no sexual predilection.
Age
The syndrome can often be recognized in the neonatal period by the typical abnormalities seen in the thumbs, the great toes, and the face.
History
- Patients may present with the following:
- Characteristic abnormalities of the head, the face, the eyes, and the skin
- Distinctive abnormalities of the fingers and the toes
- Developmental delays, growth retardation, speech delays, and/or mental retardation
- Skeletal malformations
Physical
- Facial abnormalities (see Image 1)
- Hypoplastic maxilla with narrow palate (100%)
- Prominent beaked nose (90%) (see Image 2)
- Antimongoloid palpebral fissures (88%) (see Image 1)
- Low-set/malformed ears (84%) (see Image 2)
- Strabismus (69%)
- Large anterior fontanelle (41%)
- Microcephaly (35%)
- Small mouth
- Crowded irregular teeth, high palate, short upper lip, and protuberant lower lip
- Digital abnormalities
- Broad great toes (100%) (see Image 3)
- Broad thumbs with radial angulation (87%) (see Image 2)
- Broad fingers (87%)
- Persistent fetal finger pads (31%)
- Duplicated longitudinal bracketed epiphysis (kissing delta phalanx)
- Syndactyly, polydactyly, and ulnar deviation of the thumb
- Ocular abnormalities
- Strabismus (69%)
- Nasolacrimal duct problems
- Congenital or juvenile glaucoma
- Retinal abnormalities
- Ptosis
- Severe ametropia
- Macrocornea, microphthalmos, colobomas, congenital cataract, optic nerve atrophy, and corneal keloid
- Abnormalities of growth and development
- Mental retardation, with an intelligence quotient (IQ) of 30-79; IQ of less than 50 found in more than 50% of patients
- Speech difficulties (90%)
- Hypotonia (67%)
- Growth retardation (postnatal-onset growth deficiency; average height of men is 153 cm [60 in], and average height of women is 147 cm [58 in])
- Feeding problems and echolalia
- Skeletal abnormalities
- Retarded osseous maturation (49%)
- Vertebral and sternal abnormalities (including instability of C1-C2)
- Patellar dislocation
- Patellofemoral instability
- Fourth cuneiform bones
- Joint hypermobility
- Skin findings
- Hirsutism (75%)
- Capillary nevus of the forehead or the nape (>50%)
- Keloid formation (4.87%)
- Multiple pilomatricomas, piebaldism, epidermal nevus, and keratosis pilaris atrophicans faciei
- Cardiovascular system
- Cardiac anomalies (32.6%)
- ECG abnormalities (30%)
- Cardiac arrhythmias with the use of succinylcholine
- Ventricular septal defect and patent ductus arteriosus (both are most common)
- Atrial septal defect, coarctation of the aorta, pulmonary artery stenosis, bicuspid aortic valve, hypoplastic left heart, and conduction abnormalities
- Other conditions
- Cryptorchidism (78% of males)
- Laryngeal wall collapsibility (may cause sleeping problems and difficulty during anesthesia)
- Insomnia (glossoptosis can cause sleep apnea)
- Mood disorders and obsessive compulsive disorder
- Abnormal pulmonary lobulation, bilateral vesicoureteral reflux, renal agenesis, polysplenia, thymic hypoplasia, megacolon, multiple meningiomas, congenital tracheal stenosis, epilepsy, and congenital hypothyroidism
Causes
CBP is a large nuclear protein involved in transcription regulation, chromatin remodeling, and integration of several signal transduction pathways. During organogenesis, CBP is expressed in specific cell types of the developing heart, vasculature, skin, lungs, and liver. Many of these tissues and organs are known to be affected in mutant mice lacking CBP and in patients with RSTS.
Disruption of the human CBP gene, either by gross chromosomal rearrangements or by point mutations, leads to RSTS. Translocations and inversions involving band 16p13.3 form the minority of CBP mutations, while microdeletions occur more frequently (approximately 10%). Blough et al reported that no phenotypic differences were observed among patients with partial deletion, complete deletion, and nondeletion, supporting a haploinsufficiency model for RSTS.
Roelfsema et al reported EP300 gene mutations in 3 (3.3%) of 92 patients with either true RSTS or different syndromes resembling RSTS. At present, the cause of RSTS remains unknown in approximately half of the patients. Both CBP and EP300 interact with several co-factors (p/CAF, CITED1, CITED4), which can also be involved in RSTS and would indicate further genetic heterogeneity.
Other Problems to be Considered
Faciodigitogenital syndrome (Aarskog syndrome)
Greig syndrome
Larsen syndrome
Pfeiffer syndrome
Saethre-Chotzen syndrome
Simpson-Golabi-Behmel syndrome
Weaver syndrome
Imaging Studies
- The types of imaging studies performed depend on the clinical manifestations of the patient. For example, a patient with skeletal abnormalities requires further radiologic investigations, such as CT scanning and MRI.
Other Tests
- Chromosomal karyotype analysis - To find out structural abnormalities
- Fluorescence in situ hybridization - To detect microdeletions of the CBP gene on band 16p13
- Mutation analysis of the CBP gene
Procedures
- Cardiac evaluation for patients with congenital heart disease
- Radiologic investigations for patients with skeletal abnormalities
- Visual function tests and electrophysiologic investigations for patients with eye abnormalities
- Neurologic evaluation for patients with a seizure disorder
Medical Care
The wide spectrum of clinical manifestations requires disease management tailored to the problems of each patient. Physical therapy, speech and feeding therapy, and special education are important supportive measures in infancy.
Surgical Care
Individualize surgical treatment based on findings in the patient. For example, a patient with a congenital heart defect may need cardiothoracic intervention.
Consultations
- Consult a cardiologist for evaluation of congenital heart disease.
- Consult a neurologist for evaluation of EEG and other neurologic abnormalities.
- Consult an ophthalmologist for evaluation of eye abnormalities.
- Consult an orthopedist for evaluation of skeletal abnormalities.
Further Outpatient Care
- Physical therapy, speech and feeding therapy, and special education are important supportive therapies in infancy.
Complications
- Cardiac arrhythmias can result if succinylcholine is administered.
- Sleeping problems include insomnia; glossoptosis can cause sleep apnea.
- Laryngeal wall collapsibility may cause sleeping problems and difficulty during anesthesia.
Prognosis
- Genetically based growth retardation and feeding difficulties are the principal problems hindering the development of children.
- Respiratory infections and complications resulting from congenital heart disease are primary causes of morbidity and mortality in infancy.
- Milestones in patients with RSTS are delayed.
Patient Education
- The Web site Rubinstein-Taybi Syndrome is devoted to people with RSTS and their families. Photographs of children and adults with RSTS, RSTS organizations around the world, and lists of books and other resources for families are available.
Medical/Legal Pitfalls
- Failure to pay special attention to the possibilities of airway obstruction, aspiration pneumonia, and cardiovascular dysfunction when the patient is under anesthesia (especially cardiac arrhythmias with succinylcholine use) is a pitfall.
| Media file 1:
Facial abnormalities (eg, hypoplastic maxilla, prominent beaked nose, antimongoloid palpebral fissures) and broad thumbs in a child with Rubinstein-Taybi syndrome. |
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| Media file 2:
Prominent beaked nose, low-set ears, and broad thumbs in a child with Rubinstein-Taybi syndrome. |
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| Media file 3:
Broad great toes in a child with Rubinstein-Taybi syndrome. |
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Rubinstein-Taybi Syndrome excerpt Article Last Updated: Sep 20, 2006
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