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Rubinstein–Taybi syndrome (RSTS) is a rare syndrome characterized by intellectual disability, distinctive facial features and distal limb abnormalities. RSTS is indicated by clinical features and confirmed via genetic testing. In this prenatal case series, we report four cases of RSTS with various sonographic features. Some features, such as corpus callosum dysgenesis, are nonspecific, but they may be the first sign apparent, as they appear early in pregnancy. Others, like beaked nose, shawl scrotum, premature coccygeal ossification, and overly mature scrotal sac with excessive rugae, are distinctive, but they may only be apparent in advanced gestation. [ABSTRACT FROM AUTHOR]

Aim: This case study delineates a minimally invasive and effective approach for the aesthetic and functional restoration of teeth in a patient with Rubinstein–Taybi syndrome (RTS), focusing on the challenges and strategies tailored to their specific dental care needs. Methods and Results: A 20‐year‐old patient diagnosed with RTS presented at the Pediatric Dentistry Department for a comprehensive dental assessment and care. The individual's genetic condition manifested in unique dental and craniofacial anomalies, complicating standard dental procedures. Following an initial consultation that underscored limited cooperation due to intellectual disabilities, a customized treatment plan was developed. This included behavior modification techniques to acclimate the patient to dental settings and procedures. Utilizing "simplified technologies" such as volumetric polymerization composites and self‐etching primer and adhesive systems, tooth 36 was successfully treated. The approach showcased the potential for dental care in RTS patients with minimal sedation, prioritizing patient comfort and cooperation. Conclusion: The successful dental treatment of the RTS patient highlights the importance of patient‐centered, minimally invasive approaches in managing individuals with special healthcare needs. Emphasizing continuity of care and prioritizing restorative treatments facilitated significant improvements in oral health and patient cooperation. This case contributes to the sparse literature on dental care for RTS patients, advocating for specialized strategies to address their comprehensive oral health needs. The findings underscore the necessity for interdisciplinary collaboration and innovative care protocols to ensure effective and empathetic dental treatment for individuals with RTS. [ABSTRACT FROM AUTHOR]

Rubinstein–Taybi syndrome (RSTS) is an autosomal dominant genetic disease characterized by growth retardation, psychomotor retardation, and distinctive facial features. It is primarily caused by mutations in CREBBP or EP300. In this study, we aimed to describe the clinical manifestations and genetic analyses of two cases with RSTS. Clinical analysis was performed on two cases with RSTS. Molecular diagnoses were made via whole exome sequencing, and potential pathogenic variants were filtered and selected. PCR followed by Sanger sequencing was used to verify candidate variants in the family members. Case 1 involved a 7-year-old boy (patient 1) who exhibited delayed language development, growth retardation, and intellectual disability. We did not find any other characteristics of RSTS, such as thumb or hallux abnormalities. Case 2 involved a fetus who had severe congenital heart disease, low conus medullaris, and a large gallbladder. Whole exome and Sanger sequencing results revealed that a missense mutation c.5120G>A (p. Cys1707Tyr) was present in patient 1 and that the fetus carried a heterozygous nonsense mutation c.1984C>T (p. Gln662Ter). In conclusion, whole exome sequencing combined with Sanger sequencing revealed that c.5120G>A (p. Cys1707Tyr) and c.1984C>T (p. Gln662Ter) are two new mutation sites that cause RSTS. This study expands the clinical phenotypes and is helpful in identifying gene-phenotype correlations in RSTS. [ABSTRACT FROM AUTHOR]

PurposeCase reportConclusionTo report the occurrence of unilateral, neonatal-onset congenital glaucoma in a child with Rubinstein–Taybi Syndrome (RTS).A 15-day-old male with features of RTS was presented with an enlarged corneal diameter, corneal haze, and peripheral corneal vascularization of the left eye. Ultrasound biomicroscopy of his left eye revealed iris atrophy, iridocorneal adhesions, and iris adhesions to a partially absorbed cataractous lens. Genetic evaluation of the child and the parents revealed a novel de novo heterozygous pathogenic variant in exon 5 of the CREBBP gene (NM_004380.3:c.1390C>T). A diode laser cyclophotocoagulation was performed to control the IOP in the left eye.Unilateral neonatal-onset congenital glaucoma due to iridocorneal adhesions can be a rare presentation of Rubinstein–Taybi Syndrome. [ABSTRACT FROM AUTHOR]

Background/Objectives: Rubinstein–Taybi Syndrome (RSTS-OMIM, #180849) is a rare genetic disorder associated with distinctive clinical features, including a typical craniofacial appearance, global developmental delay, intellectual disability and broad, angular thumbs and fingers. The main aim of the study was to evaluate the health problems of children with RTST, their quality of life and the impact of the disease on family functioning. In addition, we investigate whether comorbidities, autistic behavior and eating problems affect the children's overall QOL. Methods: A cross-sectional study was performed, including a total of 13 caregivers of children diagnosed with RSTS. A self-reported questionnaire [SRQ], medical records and the Pediatric Impact Module PedsQLTM 2.0, the Pediatric Quality of Life PedsQLTM 4.0 were used to obtain data on QOL and the impact of the disease on family functioning. Results: The overall QOL score for children with RSTS was x = 52.40; SD 13.01. The highest QOL was in emotional functioning (EF; x = 59.23; SD 18.69), while the lowest QOL was in physical functioning (PF; x = 48.56; SD 16.32) and social functioning (SF; x = 48.85; SD 18.84). There was a statistically significant negative correlation (p < 0.03; r = −2.01) between the age of the child and their QOL, indicating that older children had lower QOL scores. The mean overall rating for the impact of RSTS on family functioning was x = 50.00; SD 10.91. Caregivers reported the highest scores for cognitive functioning (CF; x = 64.23; SD 23.70) and family relationships (FR; x = 60.00; SD 17.17). The lowest scores were for daily activities (DA; x = 41.03; SD 17.17) and worry (W; x = 37.69; SD 18.55). Conclusions: This study provides the first comprehensive exploration of the QOL of children with RSTS) and its impact on family functioning. [ABSTRACT FROM AUTHOR]

Purpose: This case report describes a child with Duane retraction syndrome (DRS) associated with genetically confirmed Type II Rubinstein-Taybi syndrome (RTS). The purpose is to better understand the ocular manifestations of RTS and further explore the possibility that the neurodevelopmental genetic abnormality in RTS may sporadically impact ocular motor nerves. Observations: A 2-year-old male with a history of Type II RTS associated with a de novo variant of EP300 presented for a comprehensive eye examination, which revealed a left esotropia of 20 prism diopters (PD) in primary gaze with a significant left face turn, mild globe retraction on adduction in the left eye, and abduction limitation consistent with Type 1 DRS in the left eye. He underwent two strabismus surgeries and postoperatively had a satisfactory sensorimotor outcome. Conclusions: The association of DRS with RTS is rare with few prior reported cases. We present another case of DRS coupled with EP300 variant Type II RTS, though this is the first with associated manifest strabismus and compensatory torticollis requiring strabismus surgery, contributing to the phenotypic variability seen in this condition.

Copyright of Gümüshane Üniversitesi Saglik Bilimleri Dergisi is the property of Gumushane University, Faculty of Health Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A case report of a six-year and five-month-old female admitted with typical symptoms of Rubinstein-Taybi syndrome is presented. Clinical and rehabilitation settings where she acquired her reading, writing, and communication skills are described.Because of her cognitive disabilities, a multidisciplinary and long-term intervention (2014–2020) was necessary. Treatment included orthoptic, psychomotor, logopedic, occupational, and neuropsychological care. Her family and school were involved.Increased attention led to decreased dysfunctional behaviors. Test results are still below average, but there has been significant improvement. Better communication skills resulted from increased phonetic range, improved articulation, lexical-semantic structure, comprehension, and production of sentences. Digital technologies played a significant role in enhancing her communication skills, not just in social interactions but also in school activities. The patient is oriented in time and space with the help of agendas and calendars. She can express her needs and compose concise narratives. As a result of acquiring functional skills, she is better equipped to handle real-life situations, which has led to increased social and family activities.This case report highlights the importance of personalized rehabilitation programs. Obtaining an early genetic diagnosis is crucial for timely tailored rehabilitation, and any delays in this process can hinder progress. [ABSTRACT FROM AUTHOR]

Rubinstein–Taybi syndrome (RTS) is a rare genetic disorder characterized by intellectual disability, facial dysmorphisms, and enlarged thumbs and halluces. Approximately 55% of RTS cases result from pathogenic variants in the CREBBP gene, with an additional 8% linked to the EP300 gene. Given the close relationship between these two genes and their involvement in epigenomic modulation, RTS is grouped into chromatinopathies. The extensive clinical heterogeneity observed in RTS, coupled with the growing number of disorders involving the epigenetic machinery, poses a challenge to a phenotype-based diagnostic approach for these conditions. Here, we describe the first case of a patient clinically diagnosed with RTS with a CREBBP truncating variant in mosaic form. We also review previously described cases of mosaicism in CREBBP and apply clinical diagnostic guidelines to these patients, confirming the good specificity of the consensus. Nonetheless, these reports raise questions about the potential underdiagnosis of milder cases of RTS. The application of a targeted phenotype-based approach, coupled with high-depth NGS, may enhance the diagnostic yield of whole-exome sequencing (WES) in mild and mosaic conditions. [ABSTRACT FROM AUTHOR]

Colonic atresia is an uncommon cause of intestional obstruction. There is a scarcity of cases of colonic atresia described in the literature, and the pathogenesis of the disease remains unknown. Although the clinical presentation of patients with colonic atresia seldom varies, reported co-occurring anomalies vary widely; almost half of the cases involve other congenital defects. We report a case of colonic atresia that appears to have co-occurred with Rubinstein-Taybi syndrome, another rare congenital disease. Based on a literature search, we believe that this might be the first reported case of co-occurrence of these two rare anomalies.

Rubinstein-Taybi syndrome (RSTS) is a multi-system neurodevelopmental condition caused by deficiency of CREBBP (16p13.3) or EP300 (22q13.2). Müllerian agenesis, or Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, is defined as congenital agenesis of the uterus, cervix, and upper vagina without a definite genetic cause. We present a 14-year-old female with RSTS type 1 (CREBBP, c.4395-2A>C) and MRKH, the first documented in the literature. Following presentation to Gynecology for anticipatory guidance regarding future menstrual suppression and follow-up of previously diagnosed labial adhesions, exam under anesthesia revealed a single urogenital opening with cystoscopy demonstrating a normal urethra and bladder. Laboratory evaluation was consistent with peripubertal female gonadotropins and estradiol, 46,XX karyotype, and normal microarray, and a pelvic MRI confirmed Müllerian agenesis. Given this case, we assessed our cohort of females with RSTS and found that 4 of 12 individuals also had Müllerian anomalies. Gynecologic evaluation should be a part of medical care for females with RSTS, particularly in individuals with delayed menarche or abnormal menstrual history, on the basis of the observed association between RSTS and Müllerian anomalies in this case series. Although several candidate genes and copy number variants are associated with MRKH, no candidate genes in close proximity to the 16p13.3 region have been identified to explain both RSTS and MRKH in the index patient. Due to the regulatory nature of CREBBP during embryonic development, we theorize that CREBBP may play a role in the migration of Müllerian structures during embryogenesis. [ABSTRACT FROM AUTHOR]

One complex area of learning disability nursing relates to caring for people with rare neurodevelopmental disorders, which often affect physical health, mental health, social activities and family life. [ABSTRACT FROM AUTHOR]

Rubinstein-Taybi syndrome (RSTS) is a rare genetic syndrome with a wide range of phenotypic presentations, including characteristic facial features. A variety of ocular abnormalities have been described in patients with RSTS. The genetic etiology of RSTS is heterogeneous but often involves two major genes, CREBBP (cAMP-response element binding protein-binding protein) and EP300 (E1A binding protein p300), with CREBBP variants responsible for the majority of the cases. We report a new case of female patient with a novel variant in CREBBP (c.4495C>G), with clinical features consistent with RSTS. We performed a literature review to search for possible genotype-phenotype relationships between the type of variant in CREBBP and frequency of ocular presentations. A PubMed search generated 12 articles that met our inclusion criteria. With the addition of our patient, there were a total of 163 patients included for mutation analysis (164 variants given one patient had two different variants). Our review revealed that the most common variant types were frameshift (25%), gross deletion (23%), nonsense (18%), and intragenic deletions (13%). There does not appear to be an obvious hot spot location. A total of 127 patients were included for genotype-phenotype analysis of ocular features (36 patients were excluded as unable to discern variant type). The most frequent ocular features in patients with RSTS were down-slanting palpebral fissure (74%), arched eyebrows (56%), long eyelashes (52%), and strabismus (23%). Our results suggest that currently there is no clear genotype-phenotype relationship between the type of variant and frequency of associated ocular features in RSTS patients. [ABSTRACT FROM AUTHOR]

Objective. Taybi syndrome is a rare genetical disorder with the symptoms of small stature, broad thumbs and first toes, a moderate to severe intellectual handicap, and unique facial traits. The present case study aimed with diagnose and therapeutic management of pediatric patients having Rubinstein-Taybi syndrome. Study area. The case study was carried out in Jawaharlal Nehru Medical College, Acharya Vinoba Bhave Rural Hospital, Sawangi Meghe, Wardha, Maharashtra, in department of Pediatrics. The present study follows case of male child, diagnosed with different degrees of compliance, in which the therapeutic approach was determined by the severity of the patient’s conditions. Outcomes. Case study on 3 years old male child was carried out and observed with some behavioral changes like unstable mood, distractibility and impulsivity along with attention problem, aggressive nature and self-injurious behavior etc. As the syndrome does not have a particular treatment but some therapies are applied to address issues that are frequently connected to the illness. The thumbs or toes surgically repaired might enhance grip or ease pain. The study was performed as per the scientific way, based on research literatures study.

Rubinstein-Taybi syndrome (RSTS), an autosomal-dominant neurodevelopmental disorder affecting 1 in 125,000 newborns, is characterized by intellectual disability, growth retardation, facial dysmorphisms, and skeletal abnormalities. RSTS results from mutations in epigenetic machinery genes: CREBBP (~60%) or its homologous EP300 (~10%). Up to 30% of patients lack identified causative mutations, complicating early diagnosis due to phenotypic overlap with other syndromes. Here, we report a new RSTS case in an infant with atypical presentation. Wholeexome sequencing at 20 months revealed a de novo heterozygous pathogenic variant in CREBBP, c.6067C>T (p.Gln2023*), establishing the diagnosis. This case introduces a new CREBBP gene variant, illustrating the broad clinical spectrum of Mendelian disorders of the epigenetic apparatus. High WES diagnostic rates emphasize its utility in cases with challenging phenotypes spanning distinct syndromes. [ABSTRACT FROM AUTHOR]

Rubinstein–Taybi syndrome is a multisystem pathology characterized by mental retardation and delayed physical development in combination with a set of phenotypic features, which make up a recognizable pattern of the disease. This review of the literature highlights the molecular‑genetic basis and the presumed pathogenesis of the Rubinstein–Taybi syndrome, considers questions of geno‑phenotypic correlations and differential diagnosis in the group of pathologies called chromatinopathies.

We present a case of a child with Floating-Harbor Syndrome (FHS) with bilateral chorioretinal coloboma (CC). To the best of our knowledge, this is the first case report of this association. Floating- Harbor syndrome is an extremely rare autosomal dominant genetic disorder with approximately 100 cases reported. It is characterized by a series of atypical features that include short stature with delayed bone age, low birth weight, skeletal anomalies, delayed speech development, and dysmorphic facial characteristics that typically portray a triangular face, deep-set eyes, long eyelashes, and prominent nose. Our patient was examined by a pediatric ophthalmologist for the time at age of 7. Visual acuity, optical coherence tomography (OCT) and Optos imaging were collected on every visit. The patient had whole genome sequencing ordered by a pediatric geneticist to confirm Floating-Harbor syndrome. We present the patient's OCT and Optos images that illustrate the location of the patient's inferior chorioretinal coloboma in both eyes. The whole genome sequencing report collected revealed a heterozygous de novo pathogenic variant in the SRCAP gene, consistent with a Floating-Harbor syndrome diagnosis in the literature. Both genetic and systemic findings are consistent with the diagnosis of Floating-Harbor syndrome in our patient. Rubenstein-Taybi and Floating-Harbor syndrome share a similarity in molecular and physical manifestations, but because of the prevalence in Rubenstein-Taybi diagnoses, it is a syndromic condition that includes coloboma and frequently associated with each other. Therefore, a retinal exam should become part of the standard protocol for those with FHS, as proper diagnosis, examination and treatment can prevent irreversible retinal damage. [ABSTRACT FROM AUTHOR]

Background: Rubinstein–Taybi syndrome (RSTS) is a rare autosomal‐dominant genetic disease caused by variants of CREBBP (RSTS1) or EP300 (RSTS2) gene. RSTS2 is much less common, with less than 200 reported cases worldwide to date. More reports are still needed to increase the understanding of its clinical manifestations and genetic characteristics. Methods: The clinical data of two children with RSTS2 were analyzed retrospectively, and their clinical manifestations, auxiliary examinations, and mutational spectrum were summarized. Liquid chromatography–tandem mass spectrometer (LC–MS/MS) technology was used to detect the levels of steroid hormones if possible. Results: After analyzing the clinical and genetic characteristics of two boys with RSTS2 (0.7 and 10.4 years old, respectively) admitted in our hospital, we identified two novel heterozygous variants in the EP300 exon 22 (c.3750C > A, p. Cys1250*, pathogenic; c.1889A > G, p. Tyr630Cys, likely pathogenic), which could account for their phenotype. In addition to common clinical manifestations such as special facial features, microcephaly, growth retardation, intellectual disability, speech delay, congenital heart defect, recurrent respiratory infections, and immunodeficiency, we found one of them had a rare feature of adrenal insufficiency, and LC–MS/MS detection showed an overall decrease in steroid hormones. Conclusion: In our study, we identified two novel variants in the EP300 exon 22, and for the first time, we reported a case of RSTS2 associated with adrenal insufficiency, which will enrich the clinical and mutational spectrum of this syndrome. [ABSTRACT FROM AUTHOR]

Early placenta development involves cytotrophoblast differentiation into extravillous trophoblast (EVT) and syncytiotrophoblast (STB). Defective trophoblast development and function may result in severe pregnancy complications, including fetal growth restriction and pre-eclampsia. The incidence of these complications is increased in preg- nancies of fetuses affected by Rubinstein–Taybi syndrome, a developmental disorder predominantly caused by heterozygous mutations in CREB-binding protein (CREBBP) or E1A-binding protein p300 (EP300). Although the acetyltransferases CREBBP and EP300 are paralogs with many overlapping functions, the increased incidence of preg- nancy complications is specific for EP300 mutations. We hypothesized that these com- plications have their origin in early placentation and that EP300 is involved in that process. Therefore, we investigated the role of EP300 and CREBBP in trophoblast differentiation, using human trophoblast stem cells (TSCs) and trophoblast organoids. We found that pharmacological CREBBP/EP300 inhibition blocks differentiation of TSCs into both EVT and STB lineages, and results in an expansion of TSC-like cells under differentiation-inducing conditions. Specific targeting by RNA interference or CRISPR/Cas9-mediated mutagenesis demonstrated that knockdown of EP300 but not CREBBP, inhibits trophoblast differentiation, consistent with the complications seen in Rubinstein–Taybi syndrome pregnancies. By transcriptome sequencing, we identified transforming growth factor alpha (TGFA, encoding TGF-α) as being strongly upregu- lated upon EP300 knockdown. Moreover, supplementing differentiation medium with TGF- α, which is a ligand for the epidermal growth factor receptor (EGFR), likewise affected trophoblast differentiation and resulted in increased TSC-like cell proliferation. These findings suggest that EP300 facilitates trophoblast differentiation by interfering with at least EGFR signaling, pointing towards a crucial role for EP300 in early human placentation. [ABSTRACT FROM AUTHOR]

The article focuses on a case of cecal volvulus (CV) in an 11-year-old boy with Rubinstein-Taybi syndrome (RTS), highlighting the complications of gastrointestinal disorders in children with multiple disabilities. Topics include the association of CV with neurological issues, the challenges of diagnosing and treating CV in patients with RTS, and the surgical management of bowel torsion in this rare genetic condition.

Abstract Background This study was to report a novel CREBBP mutation and phenotype in a child with Rubinstein–Taybi syndrome. Methods Case report of a 9-year-old boy. Results We described the patient’s clinical manifestations in detail, and found that in addition to the typical systemic manifestations of the syndrome, the outstanding manifestation of the child was severe intellectual deficiency and prominent ocular abnormalities. Whole-exome sequencing and sanger sequencing were performed on the patient and his parents, a large intragenic deletion, covering the exon 1 region and part of the intron 1 region of the TRAP1 gene, and the entire region from intron 27 to exon 30 of the CREBBP gene (chr16:3745393-3783894) was identified on the patient. This mutation affected the CREBBP histone acetyltransferase (HAT) domain. Conclusions This findings in our patient add to the spectrum of genetic variants described in Rubinstein–Taybi syndrome and present a RSTS patient with various ocular anomalies including early onset glaucoma.

Rubinstein-Taybi syndrome (RSTS) is a rare autosomal dominant genetic disorder characterized by mental retardation, broad thumbs, and hooked nose and so on. RSTS can cause multiple organ hypoplasia and multiple system hypoplasia (such as endocrine system, digestive system, urinary system, etc.) , and even involve the skin (such as pilomatrixomas, hirsutism, etc.) . Moreover, it has been recently reported to be associated with increased risk of cancer. However, relevant research about RSTS is still very limited. By use of clinical characteristics and genetic testing, only some cases can be diagnosed, and the diagnosis for many other cases additionally requires an in-depth analysis of etiology and pathogenesis of RSTS. This paper reports a suspected RSTS patient treated in the Affiliated Hospital of Guilin Medical University. Whole exome sequencing showed that the patient has a mutation in the CREBBP gene: c.3832G>A (p.Glu1278Lys) , but her parents do not have, indicating that it is a new mutation. By the analysis of the genetic testing result with clinical characteristics, the patient was diagnosed with RSTS. It is very difficult to make a diagnosis of RSTS. By providing a detailed description of clinical features of RSTS, this report is conducive to the study of genotype-phenotype correlation of RSTS, and to clinical diagnosis and treatment of RSTS.

This history page is dedicated to the memory and achievements of the pediatric radiologist Hooshang Taybi whose name is associated with the Rubinstein-Taybi syndrome, Taybi syndrome, and Taybi-Linder syndrome. [ABSTRACT FROM AUTHOR]

Introduction: Rubinstein-Taybi syndrome (RSTS) is a rare congenital disorder characterized by developmental and intellectual disability, broadening of thumbs and halluces, and characteristic facial features. Pathogenic variants in CREBBP lead to RSTS type 1 (RSTS1) and in EP300 lead to RSTS type 2 (RSTS2). Individuals with RSTS can demonstrate a variety of behavioral and neuropsychiatric challenges, including anxiety, hyperactivity/inattention, self-injury, repetitive behaviors, and aggression. Behavioral challenges are consistently reported as one of the primary factors impacting quality of life. Despite the high prevalence and morbidity of behavioral and neuropsychiatric features of RSTS, a paucity of data exists regarding its natural history.Methods: To better understand the neurocognitive and behavioral challenges faced by individuals with RSTS, 71 caregivers of individuals with RSTS, ranging in age from one to 61 years, completed four questionnaires measuring obsessive compulsive disorder (OCD)-like symptoms, anxiety, challenging behaviors, and adaptive behavior and living skills.Results: Results revealed a high prevalence of neuropsychiatric and behavioral challenges across ages. We found specific challenging behaviors were worse in school age individuals. Scaled adaptive behavior and living skill scores differed across ages with an increased gap between typically developing peers becoming more apparent at older ages. Between types, individuals with RSTS2 had better adaptive behavior and living skills and less stereotypic behaviors but higher social phobia than individuals with RSTS1. Further, female individuals with RSTS1 appear to have increased hyperactivity. However, both groups had impairments in adaptive functioning compared to typically developing peers.Discussion: Our findings support and expand previous reports of a high prevalence of neuropsychiatric and behavioral challenges in individuals with RSTS. However, we are the first to report differences between types of RSTS. Further, age-related differences were seen with higher challenging behaviors within school-age individuals, which may improve over time, and lower adaptive behavioral skills compared to normative scales. Anticipation of these potential differential challenges across age is vital for proactive management for individuals with RSTS. Our study underscores the importance of enacting neuropsychiatric and behavioral screening earlier in childhood so appropriate management can be implemented. However, further longitudinal studies in larger cohorts are needed to understand better how behavioral and neuropsychiatric characteristics of RSTS evolve over the lifespan and differentially affect subpopulation groups.

The Rubinstein-Taybi Syndrome (RSTS) literature is limited about sensory integration, which is a foundational neurological function of the central nervous system that may affect the development of cognitive, social, and motor skills. The aim of this case report was to investigate the effects of Ayres Sensory Integration® (ASI) intervention on processing and integrating sensations, motor functions and parental goals of 3-year-old child with RSTS. Analysis of assessment data reviewed before and after treatment. Assessment collected by interview, Sensory Profile (SP), Sensory Processing Measure-Preschool (SPM-P) Home, Peabody Developmental Motor Scales-2 (PDMS-2), Gross Motor Function Measurement-88 (GMFM-88), and Gross Motor Function Classification System (GMFCS). Progress toward goals and objectives was measured with Goal Attainment Scale (GAS). ASI intervention was implemented 3 times per week for 8 weeks. At pre-intervention, SP and SPM-P Home revealed prominent sensory processing and integration difficulties in this case. PDMS-2 scores indicated the child was far behind his peers in fine and gross motor areas. In addition, systematic observations determined that the child's GMFCS level was III. After 8 weeks of ASI intervention significant improvements were found in parent reports of sensory processing in the areas of vestibular, tactile, and oral functioning on the Sensory Profile. Gains in functional motor skills were found on the GMFM-88 and the GMFCS. Consistent with these results, significant gains at or above expected levels of performance were found on GAS goals which reflected the family's main concerns for social participation, feeding, play, and movement. There are limited studies on sensory processing and integration in children with RSTS. This case report identified sensory processing and integration difficulties for the first time in a child with RSTS. Results also provide preliminary support for the positive effects of ASI intervention on sensory processing, functional motor skills, and parental goals of a child with RSTS. [ABSTRACT FROM AUTHOR]

Background: Rubinstein-Taybi syndrome is a rare disorder characterized by broad thumbs and great toes, short stature, dysmorphic facial features, eye abnormalities, cryptorchidism, and moderate to severe intellectual disability. Renal, cardiac, and dental anomalies as well as obesity may be associated with the syndrome. The patients may also have behavioral problems. They have a weak laryngeal wall that can easily collapse resulting in swallowing and breathing problems.Case report: We report a case of an infant with Rubinstein-Taybi syndrome. The present case had typical facial features, broad thumbs and great toes, right corneal opacity, and bilateral vocal cord abductor paralysis. To the best of our knowledge, no study has been conducted on bilateral vocal cord abductor paralysis in Rubinstein Taybi syndrome. In addition, the infant recovered with symptomatic treatment without tracheostomy.Conclusion: Rubinstein-Taybi syndrome is associated with various congenital anomalies, however further studies are required to investigate the rare association between Rubinstein-Taybi syndrome and bilateral vocal cord abductor paralysis in future cases.

Rubinstein-Taybi syndrome (RSTS) is a rare autosomal dominantly inherited disease characterized by slow mental and physical growth, skeletal abnormalities (broad thumbs and big toes), and dysmorphic facial features. RSTS is associated with de novo variants of the epigenetic-associated gene CREBBP. RSTS is primarily diagnosed based on clinical manifestations and genetic testing. Cutis marmorata telangiectatica congenita (CMTC) is a rare, congenital, and typically benign vascular anomaly of unknown etiology; it is described as persistent reticulated marbled erythema. The diagnosis of CMTC is largely based on clinical features, and GNA11 mutations are associated with CMTC. In this case report, we describe the case of a preterm infant (boy) with RSTS and CMTC who had a novel frameshift mutation leading to a premature stop codon in the CREBBP gene. This study adds the novel mutation c.5837dupC to the known molecular spectrum of disease-causing CREBBP gene mutations.

In this study, we focus on Rubinstein-Taybi syndrome (RTS) to explore the associations between executive function deficits and repetitive behaviors. Thirty individuals with RTS completed direct assessments of inhibition, working memory and set-shifting. Informants completed repetitive behavior and executive function questionnaires. Repetitive questions were associated with poorer inhibition and working memory. Stereotypy was associated with poorer inhibition. Adherence to routines was associated with poorer set-shifting, but only on the parental report measure. No other associations were evident. There is evidence of an association between specific repetitive behaviors and executive functioning in RTS, suggesting executive dysfunction may underpin behavioral difference in RTS. The findings point towards specific associations that are of interest for further research across populations in which repetitive behaviors are present. [ABSTRACT FROM AUTHOR]

Copyright of Fisioterapia Brasil is the property of Atlantica Editora and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The paralogous lysine acetyltransferases 3 (KAT3), CBP and P300, play critical roles during neurodevelopment, but their specific roles in neural precursors maintenance and differentiation remain obscure. In fact, it is still unclear whether these proteins are individually or jointly essential in processes such as proliferation of neural precursors, differentiation to specific neural cell types, or both. Here, we use subventricular zone-derived neurospheres as a potential ex vivo developmental model to analyze the proliferation and differentiation of neural stem cells (NSCs) lacking CBP, p300, or both proteins. The results showed that CBP and p300 are not individually essential for maintenance and proliferation of NSCs, although their combined ablation seriously compromised cell division. In turn, the absence of either of the two proteins compromised the differentiation of NSC into the neuronal and astrocytic lineages. Single-nucleus RNA sequencing analysis of neural cell cultures derived from CBP or p300 mutant neurospheres revealed divergent trajectories of neural differentiation upon CBP or p300 ablation, confirming unique functions and nonredundant roles in neural development. These findings contribute to a better understanding of the shared and individual roles of KAT3 proteins in neural differentiation and the etiology of neurodevelopmental disorders caused by their deficiency. [ABSTRACT FROM AUTHOR]

This exploratory cross‐sectional study aimed to examine the family quality of life (FQoL) among 51 Brazilian families who have children with Rubinstein–Taybi syndrome, a rare genetic disorder. Data were collected using sociodemographic and clinical data forms, as well as the Beach Center FQoL Scale, a 5‐point Likert scale ranging from "very dissatisfied" (1) to "very satisfied" (5). The average score of the overall FQoL was 3.93 ± 0.64. Families' scores were higher for family interaction (4.17 ± 0.76), parenting (4.13 ± 0.61), and disability‐related support (4.08 ± 0.76) domains, and lower for the family's emotional well‐being (3.31 ± 0.96) and physical/material well‐being (3.76 ± 0.82) domains. Family income, attendance at religious services, presence of ocular abnormalities, and aggressive behavior explained 46.2% of the variance in the overall FQoL. In summary, FQoL seems to be anchored in aspects such as family interaction and the care of parents, and be negatively affected by emotional issues, physical, and material limitations. In this context, psychological assistance should be provided to both parents and siblings whenever indicated, for improving emotional well‐being and increasing family resilience. Additionally, investments in social policies, services, and human and material resources are needed to improve the physical and material conditions of families, promote better health care, and therefore reduce the family burden. [ABSTRACT FROM AUTHOR]

Rubinstein-Taybi syndrome (RTS) is a congenital disorder with characteristic clinical manifestations. In the vast majority of cases, it is caused by mutations of the gene encoding the transcriptional co-activator cAMP-response element binding protein (CBP)-binding protein (CREBBP). It has been thought to be a tumor predisposition syndrome as RTS patients have an increased risk of developing tumors including meningiomas. However, RTS-associated meningiomas are rarely reported. We report a unique RTS-associated meningioma in which an oncogenic CREBBP mutation is identified. We also comprehensively review the reported RTS-associated meningiomas, from epidemiology and pathogenesis to clinicopathological characteristics and treatment. All RTS patients with meningiomas are female and have the exclusive mutations of CREBBP. In population-based studies RTS-associated meningiomas seem to develop at younger ages. Their pathogenesis may be driven by the CREBBP/CBP alterations resulting in aberrant signal transduction in the CBP-mediated signaling pathways. Meningiomas in RTS patients have common clinicopathological characteristics including comorbidity with other tumors, radiologically intra-osseous growth, and uncommon histopathology such as ossifying and secretory features. Given the genetic nature and rarity of RTS-associated meningiomas, further investigation of their characteristics may define molecular targets for improved therapeutic options for RTS patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc.)

Rubinstein–Taybi syndrome (RTS) is a rare genetic syndrome associated with growth delay, phenotypic facial characteristics, microcephaly, developmental delay, broad thumbs, and big toes. Most research on RTS has focused on the genotype and physical phenotype; however, several studies have described behavioral, cognitive, social, and emotional characteristics, elucidating the behavioral phenotype of RTS. The reporting of this review was informed by PRISMA guidelines. A systematic search of CINAHL, Medline, and PsychINFO was carried out in March 2021 to identify group studies describing behavioral, cognitive, emotional, psychiatric, and social characteristics in RTS. The studies were quality appraised. Characteristics reported include repetitive behavior, behaviors that challenge, intellectual disability, mental health difficulties, autism characteristics, and heightened sociability. Findings were largely consistent across studies, indicating that many characteristics are likely to form part of the behavioral phenotype of RTS. However, methodological limitations, such as a lack of appropriate comparison groups and inconsistency in measurement weaken these conclusions. There is a need for multi‐disciplinary studies, combining genetic and psychological measurement expertise within single research studies. Recommendations are made for future research studies in RTS. [ABSTRACT FROM AUTHOR]

Background: This study was to report a novel CREBBP mutation and phenotype in a child with Rubinstein–Taybi syndrome. Methods: Case report of a 9-year-old boy. Results: We described the patient's clinical manifestations in detail, and found that in addition to the typical systemic manifestations of the syndrome, the outstanding manifestation of the child was severe intellectual deficiency and prominent ocular abnormalities. Whole-exome sequencing and sanger sequencing were performed on the patient and his parents, a large intragenic deletion, covering the exon 1 region and part of the intron 1 region of the TRAP1 gene, and the entire region from intron 27 to exon 30 of the CREBBP gene (chr16:3745393-3783894) was identified on the patient. This mutation affected the CREBBP histone acetyltransferase (HAT) domain. Conclusions: This findings in our patient add to the spectrum of genetic variants described in Rubinstein–Taybi syndrome and present a RSTS patient with various ocular anomalies including early onset glaucoma. [ABSTRACT FROM AUTHOR]

Rubinstein-Taybi syndrome (RTS) is an autosomaldominant hereditary disease, which contains many skeletal and organ anomalies as well as mental retardation. Although high incidence of keloids in RTS is known, it is difficult to find a detailed report on the clinical features of keloids. In the following letter, we report an RTS patient fulfilling diagnostic criteria whosuffered from both keloids and pilomatricoma. We also performed a literature search, which identified the possible involvement of the Wnt/β-catenin signaling pathway in the pathogenesis of these two skin lesions.

Abstract Background Rubinstein–Taybi syndrome (RTS) is a rare autosomal‐dominant disease. Almost all cases are sporadic and attributed to de novo variant. Psychotic symptoms in RTS are rare and have been reported in only a few published cases. On the other hand, 22q11.2 deletion syndrome is the most common chromosomal microdeletion in humans. The 22q11.2 deletion is well recognized as a risk factor for schizophrenia. Here, we present a schizophrenic psychosis case clinically diagnosed as RTS but resolved as carrying 22q11.2 deletion by genomic analysis. Case presentation A 38‐year‐old Japanese male was admitted to our hospital due to psychotic symptoms. He had been diagnosed with RTS based on physical characteristics at the age of 9 months. On admission, we performed whole exome sequencing. He had no pathogenic variant in CREBBP or EP300. We detected 2.5 Mb deletion on 22q11.2 and one rare loss‐of‐function variant in a loss‐of‐function‐constrained gene (MTSS1) and three rare missense variants in missense‐constrained genes (CELSR3, HERC1, and TLN1). Psychotic symptoms were ameliorated by the treatment of risperidone. Conclusion The psychiatric manifestation and genomic analysis may be a clue to detecting 22q11.2 deletion syndrome in undiagnosed patients. The reason for similarity in physical characteristics in 22q11.2 deletion syndrome and RTS remains unresolved. The 22q11.2 deletion and HERC1 contribute to the patient's phenotype.

The Rubinstein–Taybi syndrome (RSTS) is a rare developmental disorder characterized by craniofacial dysmorphisms, broad thumbs and toes, intellectual disability, growth deficiency, and recurrent infections. Mutations in the cyclic adenosine monophosphate response element‐binding protein (CREB)‐binding protein (CREBBP) or in the E1A‐associated protein p300 (EP300) genes have been demonstrated in 55% (RSTS1) and up to 8% of the patients (RSTS2), respectively. Dysfunction of immune response has been reported in a subgroup of individuals with RSTS. Here we characterize two patients carrying the same EP300 variant and distinctive RSTS features (including congenital heart abnormalities, short stature, feeding problems, and gastroesophageal reflux). Whole exome sequencing did not support a dual molecular diagnosis hypothesis. Nonetheless, patients showed distinct clinical manifestations and immunological features. The most severe phenotype was associated with reduced T‐cell production and diversity. This latter feature was confirmed in a control group of four RSTS patients. [ABSTRACT FROM AUTHOR]

Rubinstein–Taybi syndrome is a rare genetic multisystem disorder with an estimated prevalence between 1 per 100,000–125,000 live births. Diagnosis is usually clinical and subsequent to birth. In fact, the rarity of the syndrome and the presence of aspecific morphologic anomalies make prenatal diagnosis challenging. The aim of our work is to analyze ultrasonographic findings, detectable with a combination of 2D and 3D techniques, which may increase the sensitivity of in utero diagnosis of this condition. We report a case of a sonographic prenatal diagnosis of broad and angulated thumbs and halluces and of an abnormal ductus venosus at 21 weeks of gestational age. These findings allowed us to suspect Rubinstein–Taybi syndrome. An accurate ultrasonographic examination may allow a prenatal diagnosis of those syndromes which are usually diagnosed after birth. [ABSTRACT FROM AUTHOR]

Background: Menke–Hennekam syndrome (MHS) is a rare and recently described syndrome consecutive to the variants in exon 30 or 31 in CREBBP (CREB-binding protein gene). The CREB-binding protein (CREBBP) and EP300 genes are two commonly expressed genes whose products possess acetyltransferase activity for histones and various other proteins. Mutations that affect these two genes are known to cause Rubinstein–Taybi syndrome (RTS); however, with the application of whole exome sequencing (WES) there were reports of variants that affect specific regions of exon 30 or 31 of these two genes but without the specific phenotype of RTS. Material and Methods: A review of the available literature was conducted, aimed at underscoring the difficulties in diagnosing MHS based on phenotype particularities. Results: Five applicable studies were identified by searching PubMed, Web of Science, and Scopus databases for publications up to November 2021 using the key terms "Menke–Hennekam syndrome" and "CREBBP". Conclusions: In this paper, we present a new case and highlight the importance of exome sequencing to identify different mutations of exons 30 and 31 of the CREBBP gene involved in MHS, and we make formal recommendations based on our literature review. [ABSTRACT FROM AUTHOR]

Introduction: Oral and dental (OD) disorders in children with Rubinstein-Taybi syndrome (RTS) are frequent but not well-known by dentists and pediatricians due to the syndrome being extremely rare. Objective: To describe the OD findings observed in a 5-year-old girl with RTS and to update the literature. Clinical case: The patient presented the following OD manifestations: prominent lower lip, narrow mouth opening, narrow and arched palate, history of angular cheilitis, micrognathia, poor lingual motility, plaque and tartar, bleeding from gingival areas due to poor dental prophylaxis, and malocclusion in the form of an anterior open bite. These OD manifestations are seen in more than 40-60% of patients with RTS. Conclusions: Professionals who treat children with RTS should become aware of the advisability of referring them to the pediatric dentist from 1 year of age and performing check-ups every 6 months. Dental management is often difficult so collaboration with anesthesiologists is recommended in order to carry out a safe and effective treatment.

Rubinstein–Taybi Syndrome (RSTS) is a rare congenital disease with distinctive facial features, broadening of the thumbs and halluces, and developmental delay. RSTS is caused by de novo genetic alterations in CREBBP and the homologous EP300 genes. In this study, we established a genetic diagnostic protocol by integrating multiplex ligation-dependent probe amplification (MLPA) and whole-exome sequencing (WES). Five patients clinically diagnosed with RSTS were enrolled for genetic testing. Germline DNA was extracted from the peripheral blood of the patients and their families. One patient (case 1) was identified as harboring a large heterozygous deletion in the 16p13.3 region, spanning the CREBBP gene. Three patients (Cases 2–4) harbored different CREBBP variants (c.2608C>T:p.Gln870Ter,c.4404_4405del:p.Thr1468fs,c.3649C>T:p.Gln1217Ter). No causative variants were identified for the fifth RSTS patient (case 5). Here, we propose a molecular diagnostic protocol that identified causative genetic alterations in 4/5 of the patients, yielding a molecular diagnostic rate of 80%. Given the rarity of RSTS, more research is needed to explore its pathogenesis and mechanism. [ABSTRACT FROM AUTHOR]