Cases Of Rubinstein-Taybi Syndrome Research Articles

Rubinstein-Taybi syndrome: a rare case report of a female child emphasizing physiotherapy on gross motor function.

Rubinstein-Taybi syndrome (RSTS) is a chromosomal segment 16p13.3 microdeletion syndrome and is characterized by CREBBP gene mutations, delay in the development of height and weight, distinctive facial features, broad and sometimes angulated thumbs and halluces, short stature, and intellectual impairment that is mild to extreme. Current literature emphasizes mainly medical, dental, and psychiatric issues in RSTS and there is no retrievable literature on physiotherapy and its role in improving motor function in RSTS. The present case report is of a baby girl of 17 months suspected case of RSTS, presented with all the features of RSTS. Delay in the acquisition of skills and development were the chief complaints. We designed a 12-week treatment regimen that concentrated mainly on transitions using principles of neurodevelopmental therapy. Gross motor function measure (GMFM 88) was taken pre- and post-treatment which showed tremendous improvement. This is the first study on the role of physiotherapy in RSTS.

Prevalence of Immunological Defects in a Cohort of 97 Rubinstein-Taybi Syndrome Patients.

Although recurrent infections in Rubinstein-Taybi syndrome (RSTS) are common, and probably multifactorial, immunological abnormalities have not been extensively described with only isolated cases or small case series of immune deficiency and dysregulation having been reported. The objective of this study was to investigate primary immunodeficiency (PID) and immune dysregulation in an international cohort of patients with RSTS. All published cases of RSTS were identified. The corresponding authors and researchers involved in the diagnosis of inborn errors of immunity or genetic syndromes were contacted to obtain up-to-date clinical and immunological information. Ninety-seven RSTS patients were identified. For 45 patients, we retrieved data from the published reports while for 52 patients, a clinical update was provided. Recurrent or severe infections, autoimmune/autoinflammatory complications, and lymphoproliferation were observed in 72.1%, 12.3%, and 8.2% of patients. Syndromic immunodeficiency was diagnosed in 46.4% of individuals. Despite the broad heterogeneity of immunodeficiency disorders, antibody defects were observed in 11.3% of subjects. In particular, these patients presented hypogammaglobulinemia associated with low B cell counts and reduction of switched memory B cell numbers. Immunoglobulin replacement therapy, antibiotic prophylaxis, and immunosuppressive treatment were employed in 16.4%, 8.2%, and 9.8% of patients, respectively. Manifestations of immune dysfunctions, affecting mostly B cells, are more common than previously recognized in patients with RSTS. Full immunological assessment is warranted in these patients, who may require detailed investigation and specific supportive treatment. Graphical Abstract.

Clinical and genetic analysis of two cases with Rubinstein-Taybi syndrome

To summarize the clinical characteristics and identify gene mutations of 2 probands with Rubinstein-Taybi syndrome (RSTS). Clinical characteristics of 2 probands with Rubinstein-Taybi syndrome were summarized. Genomic DNA was extracted from peripheral blood samples from the patients and their parents. Genomic DNA was subjected to whole exome next generation sequencing. Suspected variants were confirmed by Sanger sequencing. The two patients were characterized by typical facial features, broad thumbs and big toes, intellectual disability, and postnatal growth retardation. Two variants of the CREBBP gene, namely c.3779+1G>A and c.5052_c.5053insT, were respectively identified in the 2 patients. Among these, c.3779+1G>A was a previously known pathological mutation, while c.5052_c.5053insT was unreported previously. Both variants were predicted to be pathological. Two cases of Rubinstein-Taybi syndrome were diagnosed, which facilitated the diagnosis and genetic counselling.

A case of Rubinstein-Taybi syndrome with bicuspid aortic valve and thoracic aortic aneurysm

A case of Rubinstein-Taybi syndrome with bicuspid aortic valve and thoracic aortic aneurysm

Rubinstein-Taybi Syndrome and Epigenetic Alterations.

Rubinstein-Taybi syndrome (RSTS) is a rare genetic disorder in humans characterized by growth and psychomotor delay, abnormal gross anatomy, and mild to severe mental retardation (Rubinstein and Taybi, Am J Dis Child 105:588-608, 1963, Hennekam et al., Am J Med Genet Suppl 6:56-64, 1990). RSTS is caused by de novo mutations in epigenetics-associated genes, including the cAMP response element-binding protein (CREBBP), the gene-encoding protein referred to as CBP, and the EP300 gene, which encodes the p300 protein, a CBP homologue. Recent studies of the epigenetic mechanisms underlying cognitive functions in mice provide direct evidence for the involvement of nuclear factors (e.g., CBP) in the control of higher cognitive functions. In fact, a role for CBP in higher cognitive function is suggested by the finding that RSTS is caused by heterozygous mutations at the CBP locus (Petrij et al., Nature 376:348-351, 1995). CBP was demonstrated to possess an intrinsic histone acetyltransferase activity (Ogryzko et al., Cell 87:953-959, 1996) that is required for CREB-mediated gene expression (Korzus et al., Science 279:703-707, 1998). The intrinsic protein acetyltransferase activity in CBP might directly destabilize promoter-bound nucleosomes, facilitating the activation of transcription. Due to the complexity of developmental abnormalities and the possible genetic compensation associated with this congenital disorder, however, it is difficult to establish a direct role for CBP in cognitive function in the adult brain. Although aspects of the clinical presentation in RSTS cases have been extensively studied, a spectrum of symptoms found in RSTS patients can be accessed only after birth, and, thus, prenatal genetic tests for this extremely rare genetic disorder are seldom considered. Even though there has been intensive research on the genetic and epigenetic function of the CREBBP gene in rodents, the etiology of this devastating congenital human disorder is largely unknown.

RUBINSTEIN TAYBI SYNDROME

Rubinstein Taybi Syndrome (RTS) was first described in 1963 by Rubinsteinand Taybi. The characteristic features of this syndrome include broad thumbs and toes,facial abnormalities like hypertelorism, beaked nose, micrognathia, microcephaly and mentalretardation. Cardiac, renal, ophthalmological and various orthopedic problems can also occur.Prevalence in the general population is approximately 1 case per 300,000 persons and is as highas 1 case per 10,000 live births. There is no definite inheritance pattern so far and recurrenceis very unlikely. In some patients, multiple chromosomal anomalies have been described. Wereport here a case of Rubinstein Taybi syndrome in an 18 months old girl presented with typicalfeatures which is the first case reported in our population.

English

Rubinstein Taybi Syndrome (RTS) was first described in 1963 by Rubinsteinand Taybi. The characteristic features of this syndrome include broad thumbs and toes,facial abnormalities like hypertelorism, beaked nose, micrognathia, microcephaly and mentalretardation. Cardiac, renal, ophthalmological and various orthopedic problems can also occur.Prevalence in the general population is approximately 1 case per 300,000 persons and is as highas 1 case per 10,000 live births. There is no definite inheritance pattern so far and recurrenceis very unlikely. In some patients, multiple chromosomal anomalies have been described. Wereport here a case of Rubinstein Taybi syndrome in an 18 months old girl presented with typicalfeatures which is the first case reported in our population.

Clinical and molecular characterization of Rubinstein‐Taybi syndrome patients carrying distinct novel mutations of the EP300 gene

Rubinstein-Taybi syndrome (RSTS) is a rare congenital neurodevelopmental disorder characterized by postnatal growth deficiency, skeletal abnormalities, dysmorphic features and cognitive deficit. Mutations in two genes, CREBBP and EP300, encoding two homologous transcriptional co-activators, have been identified in ˜55% and ˜3-5% of affected individuals, respectively. To date, only eight EP300-mutated RSTS patients have been described and 12 additional mutations are reported in the database LOVD. In this study, EP300 analysis was performed on 33 CREBBP-negative RSTS patients leading to the identification of six unreported germline EP300 alterations comprising one deletion and five point mutations. All six patients showed a convincing, albeit mild, RSTS phenotype with minor skeletal anomalies, slight cognitive impairment and few major malformations. Beyond the expansion of the RSTS-EP300-mutated cohort, this study indicates that EP300-related RSTS cases occur more frequently than previously thought (˜8% vs 3-5%); furthermore, the characterization of novel EP300 mutations in RSTS patients will enhance the clinical practice and genotype-phenotype correlations.

Rubinstein-taybi syndrome: Clinical profile of 11 patients and review of literature

BACKGROUND:Rubinstein-Taybi syndrome (RSTS) is a rare congenital neurodevelopmental disorder, characterized by postnatal growth deficiency, typical dysmorphic features, broad thumbs and toes, and mental retardation. Very few cases are reported in literature from developing countries. Diagnosis is often delayed due to non-familiarity with the characteristic features of this syndrome.AIMS:To report 11 cases of RSTS and to review the current literature.SETTINGS AND DESIGN:Retrospective study conducted in genetic and metabolic unit of a tertiary care teaching hospital in north India over a period of 3½ years.MATERIALS AND METHODS:11 patients with diagnosis of RSTS were identified, and their case sheets were reviewed.RESULTS:Developmental delay was presenting complaint in 10 patients, and seizure in 1 case. 7 patients had microcephaly (head circumference below −3 SD), and a prominent beaked nose was seen in 9 patients. The intelligence quotient (IQ) varied from 22-62 in 7 patients who had mental retardation. The most notable features in hands were broadness, shortening, and flattening of the distal phalanx of thumbs or great toes. Additionally, we also noted webbing of neck, microphthalmia, and pachygyria (on MRI brain) in 1 patient each.CONCLUSIONS:The diagnosis of RSTS is primarily clinical and based on characteristic phenotype that is often combined with a variety of somatic anomalies. An early diagnosis facilitates appropriate genetic counseling and in planning the management.

Exon deletions of the EP300 and CREBBP genes in two children with Rubinstein–Taybi syndrome detected by aCGH

We demonstrate the utility of an exon coverage microarray platform in detecting intragenic deletions: one in exons 24-27 of the EP300 gene and another in exons 27 and 28 of the CREBBP gene in two patients with Rubinstein-Taybi syndrome (RSTS). RSTS is a heterogeneous disorder in which approximately 45-55% of cases result from deletion or mutations in the CREBBP gene and an unknown portion of cases result from gene changes in EP300. The first case is a 3-year-old female with an exonic deletion of the EP300 gene who has classic facial features of RSTS without the thumb and great toe anomalies, consistent with the milder skeletal phenotype that has been described in other RSTS cases with EP300 mutations. In addition, the mother of this patient also had preeclampsia during pregnancy, which has been infrequently reported. The second case is a newborn male who has the classical features of RSTS. Our results illustrate that exon-targeted array comparative genomic hybridization (aCGH) is a powerful tool for detecting clinically significant intragenic rearrangements that would be otherwise missed by aCGH platforms lacking sufficient exonic coverage or sequencing of the gene of interest.

A case of Rubinstein-Taybi Syndrome with a CREBbinding protein gene mutation

Rubinstein-Taybi syndrome (RTS) is a congenital disorder characterized by typical facial features, broad thumbs and toes, with mental retardation. Additionally, tumors, keloids and various congenital anomalies including congenital heart defects have been reported in RTS patients. In about 50% of the patients, mutations in the CREB binding protein (CREBBP) have been found, which are understood to be associated with cell growth and proliferation. Here, we describe a typical RTS patient with Arnold-Chiari malformation. A mutation in the CREBBP gene, c.4944_4945insC, was identified by mutational analysis.

A case of Rubinstein Taybi syndrome

The Journal is the primary organ of Continuing Paediatric Medical Education in Sri Lanka. The journal also has a website. Free full text access is available for all readers.The Sri Lanka Journal of Child Health is now indexed in SciVerse Scopus (Source Record ID 19900193609), Index Medicus for South-East Asia Region (IMSEAR), CABI (Centre for Agriculture and Bioscience International Global Health Database), DOAJ and is available in Google, as well as Google Scholar.The policies of the journal are modelled on the Committee on Publication Ethics (COPE) Guidelines on Principles of Transparency and Best Practice in Scholarly Publishing. Sri Lanka Journal of Child Health is recognised by the International Committee of Medical Journal Editors (ICMJE) as a publication following the ICMJE Recommendations.

What's right with my mouse model? New insights into the molecular and cellular basis of cognition from mouse models of Rubinstein-Taybi Syndrome: Table 1.

What's right with my mouse model? New insights into the molecular and cellular basis of cognition from mouse models of Rubinstein-Taybi Syndrome: Table 1.

Possible case of Rubinstein-Taybi syndrome in a prehistoric skeleton from west-central Illinois

I describe an adult female skeleton (#Yo3-96) from the Yokem Mound skeletal series that had microcephaly; mild micrognathia; a broad nasal bridge; orbital hypertelorism; hypoplasia of the first metacarpals; pes planus; anomalies of the cervical spine, ribs, and sternum; and delayed epiphyseal remodeling of the radii and tibiae. Because the Yokem series has been subject to extensive measurement in previous studies, Yo3-96 can be characterized metrically and compared with others from her population. A differential diagnosis is made by comparing the available skeletal evidence with the known syndromes characterized by radial ray dysplasia. It is suggested that Yo3-96 represents the earliest known case of Rubinstein-Taybi syndrome, a mental retardation syndrome that has been described in individuals from several modern populations.

Possible case of Rubinstein-Taybi syndrome in a prehistoric skeleton from west-central Illinois

Possible case of Rubinstein-Taybi syndrome in a prehistoric skeleton from west-central Illinois

Confirmation of assignment of a locus for Rubinstein-Taybi syndrome gene to 16p13.3.

A two month-old girl was diagnosed as a case of Rubinstein-Taybi syndrome (RTS) on typical facial dysmorphism, broad and duplicated distal phalanges of thumbs and halluces, growth retardation and psychomotor development delay. Chromosome analysis demonstrated a de novo pericentric inversion of one chromosome 16: 46,XX,inv(16)(p13.3;q13). This association confirms assignment of a locus for RTS gene to 16p13.3, as two others translocations involving the same breakpoint have already been reported.

Rubinstein-Taybi syndrome

Rubinstein-Taybi (broad thumb and big toe) syndrome, is characterized by mental and motor retardation and skeletal deformities of which broad thumb and large first toe are the most obvious. In addition, defects of the cardiovascular system and the urinary tract may be present. A case of Rubinstein-Taybi syndrome in a boy is presented.

Ｒｕｂｉｎｓｔｅｉｎ‐Ｔａｙｂｉ症候群の５例

Rubinstein and Taybi reported seven cases with mental retardation and some anomalies. The symptoms in common of this syndrome were the large thumbs and great toes, facial peculiarities, mental retardation, and repeated respiratory infections. Else, this syndrome was attended with dwarfism, microcephalia, highly arched palated, etc.As we have experienced five cases of Rubinstein-Taybi syndrome, we described them with outline. For chidren with mental retardation, this syndrom is by no means unusual, and needs the differential diagnosis for the other diseases and early therapy. We have compared the early therapy case with no therapy case for mental retardation, and noted the clear difference in the mental development.

Three cases of Rubinstein-Taybi syndrome

Three cases of Rubinstein-Taybi syndrome