Rubinstein-Taybi syndrome (RTS) is a genetic disorder characterised by several features:
Broad big toes
Recently, some patients have demonstrated mutations and alteraation in the CREB binding protein (CREBBP or CBP) gene, localized to chromosome band 16p13.3
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/
Other Diagnostic Testing
Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Broad thumbs syndrome
Broad thumb-hallux syndrome
- Submicroscopic deletions at 16p13.3 in Rubinstein-Taybi syndrome: frequency and clinical manifestations in a North American population.
Wallerstein R, Anderson CE, Hay B, Gupta P, Gibas L, Ansari K, Cowchock FS, Weinblatt V, Reid C, Levitas A, Jackson L.
Division of Medical Genetics, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
J Med Genet. 1997 Mar;34(3):203-6. Abstract quote
Rubinstein-Taybi syndrome (RTS) is a well delineated multiple congenital anomaly syndrome characterised by mental retardation, broad thumbs and toes, short stature, and specific facial features. The recent localisation of the disorder to 16p13.3 and subsequent identification of a submicroscopic deletion of this region in RTS patients led us to screen a large cohort of affected subjects using the RT1 probe.
Among 64 patients with clinical evidence of RTS, seven (11%) had a deletion. Another patient had a translocation of the region without evidence of a deletion. The features of coloboma, growth retardation, naevus flammeus, and hypotonia have a positive predictive value for the presence of an RT1 deletion.
Because of the relatively low frequency of deletions in RTS, the RT1 probe is useful in diagnostic confirmation, but has limited use as a screening tool.
AGE SEX GEOGRAPHY EPIDEMIOLOGIC ASSOCIATIONS
DISEASE ASSOCIATIONS CHARACTERIZATION CHURG-STRAUSS SYNDROME
J Eur Acad Dermatol Venereol. 2004 Sep;18(5):607-10. Abstract quote
We report an unusual association of multiple perforating and non-perforating pilomatricomas with Churg-Strauss syndrome, and a dysmorphic syndrome evocative of Rubinstein-Taybi syndrome.
These syndromes may be independent, but these rare diseases and genetic abnormalities may be linked together.
J Neurosurg. 2005 Jan;102(1):167-8 Abstract quote
The authors report a case of multiple meningiomas in a 37-year-old woman with Rubinstein-Taybi syndrome.
The patient harbored a bifrontal ossifying meningioma and multiple intracranial meningiomas.
She underwent surgery for the frontal ossifying meningioma and a right frontoparietal meningioma.
J Chin Med Assoc. 2004 Dec;67(12):633-6. Abstract quote
Pilomatrixoma is a benign skin appendage tumor that commonly occurs as a solitary lesion and is not usually hereditary. There is evidence to suggest that patients with a family history of multiple pilomatrixomas have a high probability of autosomal dominant disorders such as myotonic dystrophy, Gardner syndrome, and Rubinstein-Taybi syndrome.
In January 2004, a case was reported of an 8-year-old girl with 2 progressively enlarged facial masses. One of them was excised and diagnosed as pilomatrixoma. Coincidently, her 13-year-old sister had the same type of tumor when she was 4 years old. We report this unusual case and review the literature. Pilomatrixoma has not been widely reported in the head and neck surgery literature.
This benign tumor may be misdiagnosed as a carcinoma, resulting in unnecessary aggressive therapy. Otolaryngologists should therefore note the clinical and pathologic characteristics of these symptoms.
PATHOGENESIS CHARACTERIZATION CREBBP GENE MUTATIONS
- DNA sequencing of CREBBP demonstrates mutations in 56% of patients with Rubinstein-Taybi syndrome (RSTS) and in another patient with incomplete RSTS.
Bartsch O, Schmidt S, Richter M, Morlot S, Seemanova E, Wiebe G, Rasi S.
Institut fur Humangenetik, Klinikum, Universitat Mainz, 55101, Mainz, Germany.
Hum Genet. 2005 Sep;117(5):485-93. Epub 2005 Jul 14. Abstract quote
Rubinstein-Taybi syndrome (RSTS) is a distinct dominant disorder characterized by short stature, typical face, broad angulated thumbs and halluces, and mental retardation.
The RSTS can be caused by chromosomal microdeletions and molecular mutations in the CREBBP gene; however, relatively few mutations have been reported to date.
Here, we aimed to determine the rate of point mutations and other small molecular lesions in true RSTS and possible mild variants, by using genomic DNA sequencing. A consecutive series of patients including 17 patients from our previous study was investigated.
We identified 19 causative mutations of CREBBP in a total of 45 patients representing three different diagnostic groups: (a) 17 mutations in 30 patients with unequivocal RSTS (detection rate 56.6%), (b) two mutations in eight patients with features suggestive of RSTS ("moderate or incomplete RSTS", detection rate 25%), and (c) no mutation in seven patients with undiagnosed syndromes and isolated features of RSTS. In general, the mutations were distributed without hot spots and most were unique; however, three recurrent mutations (R370X, R1664H, and N1978S) were identified. Furthermore, we detected 15 different intragenic polymorphisms, including two non-synonymous coding polymorphisms, L551I and Q2208H.
We report not only the highest detection rate (56.6%) of CREBBP mutations in patients with RSTS to date, but also the second missense mutation (N1978S) in a patient with moderate or incomplete RSTS. Previous studies have identified cytogenetic deletions in the CREBBP gene in eight to 12% of patients and very recently, Roelfsema et al. reported EP300 gene mutations in three of 92 (3.3%) patients with either true RSTS or different syndromes resembling RSTS.
Our 56.6% detection rate of molecular mutations in CREBBP in patients with unequivocal RSTS supports the new concept that RSTS is a genetically heterogeneous disorder and furthermore, indicates that RSTS may be caused by gene/s other than CREBBP in up to 30% of cases.
Skeletal Radiol. 2004 Jun;33(6):345-51. Epub 2004 May 6. Abstract quote
BACKGROUND: The delta phalanx, also known as the delta bone, or longitudinal epiphyseal bracket (LEB), has been described in a variety of syndromes and dysplasias. However, the "kissing delta phalanx" is not as well recognized in the literature; it consists of a duplicated longitudinal bracketed epiphysis, or a complex of two adjacent delta bones, with opposing convex portions facing each other. Magnetic resonance imaging of the kissing delta phalanx has not been previously described.
OBJECTIVE: To describe the evolution, variation and associated osseous anomalies of the kissing delta phalanx in three patients with distinct distal limb malformations using both plain films and magnetic resonance imaging.
RESULTS: Patient 1 had Rubinstein-Taybi syndrome and, in addition to a kissing delta phalanx in both feet, had corresponding delta metatarsals (MT1). Patient 2 had Cenani-Lenz syndactyly with distinct variation of the kissing delta phalanx in each hand. He had a disorganized appearance to the phalanges, metacarpal fusions and carpal coalitions. Patient 3 had an isolated oligosyndactyly of the left hand with metacarpal fusions and carpal coalitions. All three patients were followed over time. We describe two types of kissing delta phalanges: separated (without fusion of the corresponding epiphyseal brackets) and nonseparated (with fusion of the corresponding epiphyseal brackets). Both types can be seen in the same patient and are a reflection of the relative degree of segmentation of the two delta bones.
CONCLUSION: The appearance of this rare osseous abnormality changes with time and can be found in a limited number of uncommon disorders. It can also be found in association with other osseous anomalies of the distal extremities; therefore magnetic resonance imaging early in life can greatly assist in surgical planning. Recognition of the kissing delta phalanx may be an important radiological clue to diagnosis of these rare disorders.
LABORATORY MARKERS GENETIC ANALYSIS
- Diagnostic analysis of the Rubinstein-Taybi syndrome: five cosmids should be used for microdeletion detection and low number of protein truncating mutations.
Petrij F, Dauwerse HG, Blough RI, Giles RH, van der Smagt JJ, Wallerstein R, Maaswinkel-Mooy PD, van Karnebeek CD, van Ommen GJ, van Haeringen A, Rubinstein JH, Saal HM, Hennekam RC, Peters DJ, Breuning MH.
Departments of Human and Clinical Genetics, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands.
J Med Genet. 2000 Mar;37(3):168-76. Abstract quote
Rubinstein-Taybi syndrome (RTS) is a malformation syndrome characterised by facial abnormalities, broad thumbs, broad big toes, and mental retardation. In a subset of RTS patients, microdeletions, translocations, and inversions involving chromosome band 16p13.3 can be detected.
We have previously shown that disruption of the human CREB binding protein (CREBBP or CBP) gene, either by these gross chromosomal rearrangements or by point mutations, leads to RTS. CBP is a large nuclear protein involved in transcription regulation, chromatin remodelling, and the integration of several different signal transduction pathways.
Here we report diagnostic analysis of CBP in 194 RTS patients, divided into several subsets. In one case the mother is also suspect of having RTS. Analyses of the entire CBP gene by the protein truncation test showed 4/37 truncating mutations. Two point mutations, one 11 bp deletion, and one mutation affecting the splicing of the second exon were detected by subsequent sequencing. Screening the CBP gene for larger deletions, by using different cosmid probes in FISH, showed 14/171 microdeletions.
Using five cosmid probes that contain the entire gene, we found 8/89 microdeletions of which 4/8 were 5' or interstitial. This last subset of microdeletions would not have been detected using the commonly used 3' probe RT1, showing the necessity of using all five probes.
Eur Rev Med Pharmacol Sci. 1998 Mar-Apr;2(2):81-7. Abstract quote
In 1963 Rubinstein and Taybi described a new syndrome characterized by broad thumbs and toes, facial abnormalities and mental retardation.
The syndrome can be observed in the neonatal period by typical thumbs, halluces and facial abnormalities. The prevalence in the general population is unknown, however the disorder is not rare and is present in about 1:600 patients in mental retardation clinics.
At the present time there is no definite inheritance pattern and recurrence is very unlikely. 18 different chromosomal anomalies have been identified in some patients with this syndrome.
In this paper we identify a typical case and review the symptoms and signs of the RT syndrome and meta-analyze 732 cases.
VARIANTS CERVICAL VERTEBRAE ANOMALY
Congenital anomaly of cervical vertebrae is a major complication of Rubinstein-Taybi syndrome.
Yamamoto T, Kurosawa K, Masuno M, Okuzumi S, Kondo S, Miyama S, Okamoto N, Aida N, Nishimura G.
Department of Medical Genetics, Clinical Research Institute, Kanagawa Children's Medical Center (KCMC), Yokohama, Japan.
Am J Med Genet A. 2005 Jun 1;135(2):130-3. Abstract quote
Rubinstein-Taybi syndrome (RTS; MIM# 180849) is a well-known malformation syndrome, characterized by broad thumbs and halluces, a characteristic facies, short stature, and mental retardation.
RTS is accompanied by a variety of morbid complications, particularly of the skeleton. Based on the experience of five RTS patients with malformation of the craniovertebral junction, we draw attention to previously unrecognized life-threatening complications of RTS, including instability of C1-C2, os odontoideum, hypoplasia of the dens, and fusion of the cervical vertebrae. One patient developed severe cervical myelopathy.
Malformation of the cervical spine may be a common syndromic constituent of RTS, to which special attention should be paid to prevent its neurologic sequelae.
Br J Ophthalmol. 2000 Oct;84(10):1177-84. Abstract quote
AIMS: To delineate the nature and frequency of ocular pathology in Rubinstein-Taybi syndrome (RTs).
METHODS: Literature was searched for reports describing ocular symptoms in patients with RTs. 24 RTs patients (out of a total of 73 Dutch known RTs individuals) were selected for ophthalmological and electrophysiological examination, selection being based only on the distance between a patient's residence and the place of investigation.
RESULTS: Most frequently reported eye anomalies in the literature were lacrimal duct obstruction, corneal abnormalities, congenital glaucoma, congenital cataract, and colobomata. Abnormalities of almost any eye segment have been published in case reports. Ophthalmological examination of 24 Dutch RTs patients showed a visual acuity </=0.3 in five patients. The most frequently found eye anomalies were nasolacrimal duct problems (six patients), cataract (six patients, four congenital), and retinal abnormalities (18 patients). VEPs showed an abnormal waveform in 15 patients. It was possible to perform an ERG in 18 patients, of whom 14 were abnormal (eight showed cone dysfunction, six cone-rod dysfunction).
CONCLUSIONS: Ocular abnormalities occur in the majority of RTs patients and can be remarkably diverse. The high frequency of retinal dysfunction (78%) has not been described before. With age, retinal as well as electrophysiological abnormalities occur more frequently. In four patients no signs of retinal dysfunction were observed, indicating phenotypic heterogeneity. Further cytogenetic and molecular examination of the patients is needed before it becomes clear if this also represents genetic heterogeneity. Because of the high frequency of ocular abnormalities, visual function tests and electrophysiological investigations should be performed in every RTs patient at regular intervals.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL PILOMATRIXOMA
CHARACTERIZATION SPECIAL STAINS IMMUNOPEROXIDASE ELECTRON MICROSCOPY
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES GENERAL
- A case with some clinical findings overlapping to Rubinstein-Taybi, Rubinstein-Taybi-like syndrome or multiple pterygium syndrome: coincidental findings or a new entity?
Kargi AE, Balci S, Akoz T, Kargi S, Erdogan B.
Department of Plastic and Reconstructive Surgery, Ankara Numune Community Hospital, Turkey.
Turk J Pediatr. 2001 Apr-Jun;43(2):166-71. Abstract quote
We report a case with broad, deviated thumb and big, duplicated, deviated toes resembling Rubinstein-Taybi syndrome. But the patient did not have severe mental retardation as in Rubinstein-Taybi syndrome and had no microdeletions on chromosome 16 by FISH-based assay.
This patient had mild webbing as seen in multiple pterygium syndrome, but broad-deviated thumb has not been reported in this syndrome.
We discuss whether these are coincidental or overlapping findings or whether this is a possible new clinical entity.
PROGNOSIS CHARACTERIZATION GENERAL
Congenit Anom (Kyoto). 2005 Jun;45(2):65-6. Abstract quote
Rubinstein-Taybi syndrome (RTS), also known as 'broad thumbs syndrome' or 'broad thumb-hallux syndrome', is a malformation syndrome characterized by the triad of broad thumbs or first toes, a peculiar facial expression called 'comical face' and mental retardation. Although various malformations are combined with the triad, polydactyly is rare.
We treated a male patient with RTS complicated by postaxial polydactyly of the foot. His clinical course was different from typical patients with polydactyly, especially in the aspect of walking development.
Osteoplasty-combined surgery, which was ideal for anatomical reconstruction, was performed on the patient at 2 years and 11 months of age. A 4-year follow-up period was required until there was an improvement of dysbasia.
TREATMENT CHARACTERIZATION GENERAL
Am J Med Genet A. 2003 Jun 1;119(2):101-10. Abstract quote
Children and adults with Rubinstein-Taybi Syndrome have specific medical conditions that occur with greater frequency than the general population.
Based on the available information from the literature and clinical experience, recommendations for specific surveillance and interventions are made to guide those clinicians caring for individuals with Rubinstein-Taybi Syndrome. This is a first attempt at medical guidelines for individuals with RTS in the United States.
On-going research is needed in many areas to guide decisions in medical care and allow for refinement of these medical guidelines.
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
Basic Principles of Disease
Learn the basic disease classifications of cancers, infections, and inflammation
Commonly Used Terms
This is a glossary of terms often found in a pathology report.
Learn how a pathologist makes a diagnosis using a microscope
Surgical Pathology Report
Examine an actual biopsy report to understand what each section means
Understand the tools the pathologist utilizes to aid in the diagnosis
How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate
Recent teaching cases and lectures presented in conferences
Pathologists Who Make A Difference
Search for a Physician Specialist
Last Updated September 20, 2005
mail to The Doctor's Doctor with
questions or comments about this web site.
Read the Medical Disclaimer.
Copyright © The Doctor's Doctor