Quality of life of Brazilian families who have children with Rubinstein-Taybi syndrome: An exploratory cross-sectional study.

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.

The natural history of adults with Rubinstein-Taybi syndrome: a families-reported experience.

The existing knowledge about morbidity in adults with Rubinstein-Taybi syndrome (RTS) is limited and detailed data on their natural history and response to management are needed for optimal care in later life. We formed an international, multidisciplinary working group that developed an accessible questionnaire including key issues about adults with RTS and disseminated this to all known RTS support groups via social media. We report the observations from a cohort of 87 adult individuals of whom 43 had a molecularly confirmed diagnosis. The adult natural history of RTS is defined by prevalent behavioural/psychiatric problems (83%), gastrointestinal problems (73%) that are represented mainly by constipation; and sleep problems (62%) that manifest in a consistent pattern of sleep apnoea, difficulty staying asleep and an increased need for sleep. Furthermore, over than half of the RTS individuals (65%) had skin and adnexa-related problems. Half of the individuals receive multidisciplinary follow-up and required surgery at least once, and most frequently more than once, during adulthood. Our data confirm that adults with RTS enjoy both social and occupational possibilities, show a variegated experience of everyday life but experience a significant morbidity and ongoing medical issues which do not appear to be as coordinated and multidisciplinary managed as in paediatric patients. We highlight the need for optimal care in a multidisciplinary setting including the pivotal role of specialists for adult care.

Waiting for a diagnosis in Rubinstein-Taybi: The journey from "ignorance is bliss" to the value of "a label".

The journey to receiving a diagnosis for rare genetic disease can be long and emotionally impactful. This study describes parental experiences of receiving their child's diagnosis of Rubinstein-Taybi syndrome (RTS), a rare genetic condition characterized by growth and developmental delay together with dysmorphic features. Parents from the RTS Australia support group participated in qualitative, semi-structured phone interviews, which were transcribed verbatim and thematically analyzed. Questions focused on psychosocial challenges and benefits pre and post-diagnosis. Ten mothers and three fathers participated, with the mean age of diagnosis being 8 months. Parents reported positive psychological effects from a slight delay in diagnosis, and negative effects from an extended diagnostic delay, suggesting the ideal time for a parent to receive a diagnosis lies in the post attachment stage, prior to the development of significant parental concerns. This stage would vary depending on condition severity. Parents desired a diagnosis to reduce uncertainty; however, uncertainty remained post diagnosis, and shifted its focus from broadly encompassing etiology and prognosis, to specifically focusing on concerns regarding severity within the spectrum. Perceived benefits of a diagnosis mainly centered on the provision of a label. Parents articulated that a label increased social acceptance, enhanced coping, promoted communication, and improved access to medical, financial, and support services. This study provides insights into the experience of families prior to and following receipt of a diagnosis. It also highlights the possibility of an optimal time window to receive a diagnosis; in which bonding is maximized and parental distress is minimized.

Rubinstein-Taybi syndrome in Chinese population with four novel mutations.

Rubinstein-Taybi syndrome (RSTS, OMIM*180849) is a rare autosomal dominant disorder, characterized by distinctive facial features, short stature, broad and often angulated thumbs and halluces, with occasional congenital anomalies. Characteristic facial dysmorphic features include downslanting palpebral fissures, low hanging columella. RSTS is caused by pathogenic variants in two ubiquitously expressed and highly homologous genes, CREBBP (OMIM*600140) and EP300 (OMIM*600140). Clinical features were well reported especially in Caucasian ethnicity. We would like to report the clinical phenotype of RSTS in our Chinese population and highlight four novel mutations in CREBBP gene.

Rubinstein-Taybi syndrome in diverse populations.

Rubinstein-Taybi syndrome (RSTS) is an autosomal dominant disorder, caused by loss-of-function variants in CREBBP or EP300. Affected individuals present with distinctive craniofacial features, broad thumbs and/or halluces, and intellectual disability. RSTS phenotype has been well characterized in individuals of European descent but not in other populations. In this study, individuals from diverse populations with RSTS were assessed by clinical examination and facial analysis technology. Clinical data of 38 individuals from 14 different countries were analyzed. The median age was 7 years (age range: 7 months to 47 years), and 63% were females. The most common phenotypic features in all population groups included broad thumbs and/or halluces in 97%, convex nasal ridge in 94%, and arched eyebrows in 92%. Face images of 87 individuals with RSTS (age range: 2 months to 47 years) were collected for evaluation using facial analysis technology. We compared images from 82 individuals with RSTS against 82 age- and sex-matched controls and obtained an area under the receiver operating characteristic curve (AUC) of 0.99 (p < .001), demonstrating excellent discrimination efficacy. The discrimination was, however, poor in the African group (AUC: 0.79; p = .145). Individuals with EP300 variants were more effectively discriminated (AUC: 0.95) compared with those with CREBBP variants (AUC: 0.93). This study shows that clinical examination combined with facial analysis technology may enable earlier and improved diagnosis of RSTS in diverse populations.

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.

Benign and malignant tumors in Rubinstein-Taybi syndrome.

Rubinstein-Taybi syndrome (RSTS) is a multiple congenital anomalies syndrome associated with mutations in CREBBP (70%) and EP300 (5-10%). Previous reports have suggested an increased incidence of specific benign and possibly also malignant tumors. We identified all known individuals diagnosed with RSTS in the Netherlands until 2015 (n = 87) and studied the incidence and character of neoplastic tumors in relation to their CREBBP/EP300 alterations. The population-based Dutch RSTS data are compared to similar data of the Dutch general population and to an overview of case reports and series of all RSTS individuals with tumors reported in the literature to date. Using the Nationwide Network and Registry of Histopathology and Cytopathology in the Netherlands (PALGA Foundation), 35 benign and malignant tumors were observed in 26/87 individuals. Meningiomas and pilomatricomas were the most frequent benign tumors and their incidence was significantly elevated in comparison to the general Dutch population. Five malignant tumors were observed in four persons with RSTS (medulloblastoma; diffuse large-cell B-cell lymphoma; breast cancer; non-small cell lung carcinoma; colon carcinoma). No clear genotype-phenotype correlation became evident. The Dutch population-based data and reported case studies underscore the increased incidence of meningiomas and pilomatricomas in individuals with RSTS. There is no supporting evidence for an increased risk for malignant tumors in individuals with RSTS, however, due to the small numbers this risk may not be fully dismissed.

Recommendations for Cancer Surveillance in Individuals with RASopathies and Other Rare Genetic Conditions with Increased Cancer Risk.

In October 2016, the American Association for Cancer Research held a meeting of international childhood cancer predisposition syndrome experts to evaluate the current knowledge of these syndromes and to propose consensus surveillance recommendations. Herein, we summarize clinical and genetic aspects of RASopathies and Sotos, Weaver, Rubinstein-Taybi, Schinzel-Giedion, and NKX2-1 syndromes as well as specific metabolic disorders known to be associated with increased childhood cancer risk. In addition, the expert panel reviewed whether sufficient data exist to make a recommendation that all patients with these disorders be offered cancer surveillance. For all syndromes, the panel recommends increased awareness and prompt assessment of clinical symptoms. Patients with Costello syndrome have the highest cancer risk, and cancer surveillance should be considered. Regular physical examinations and complete blood counts can be performed in infants with Noonan syndrome if specific PTPN11 or KRAS mutations are present, and in patients with CBL syndrome. Also, the high brain tumor risk in patients with L-2 hydroxyglutaric aciduria may warrant regular screening with brain MRIs. For most syndromes, surveillance may be needed for nonmalignant health problems. Clin Cancer Res; 23(12); e83-e90. ©2017 AACRSee all articles in the online-only CCR Pediatric Oncology Series.

Dissociation of Cross-Sectional Trajectories for Verbal and Visuo-Spatial Working Memory Development in Rubinstein-Taybi Syndrome.

Working memory (WM) impairments might amplify behavioural difference in genetic syndromes. Murine models of Rubinstein-Taybi syndrome (RTS) evidence memory impairments but there is limited research on memory in RTS. Individuals with RTS and typically developing children completed WM tasks, with participants with RTS completing an IQ assessment and parents/carers completing the Vineland Adaptive Behavior Scales. A cross-sectional trajectory analysis was conducted. There were significant WM span deficits in RTS relative to mental age. Verbal WM span was positively associated with mental age; however, this was not observed for visuo-spatial span. There is a dissociation between WM domains in RTS. Individuals may have difficulties with tasks relying on WM span, above difficulties predicted by overall ability.

Adults with Rubinstein-Taybi syndrome.

Information in the medical literature regarding adults with genetic syndromes is limited, making the care of these patients challenging. We conducted a questionnaire study of adults with Rubinstein-Taybi syndrome that addressed medical problems, education, independence, and behavior. The most common medical problems included short stature, obesity, visual difficulties, keloids, eating problems, spine curvature, and joint problems. The adults had typically moderate mental retardation, but most achieved some independence in self-care and communication; many participated in supported work situations. However, approximately one-third were said to have some decreased abilities over time. Behavior problems were common and often worsened with age. Very few of the study participants were seeing a geneticist as an adult. Long-term involvement of geneticists and education of adult primary care providers may help with many of the challenges facing adults with RTS and their families.

[Myopia in systemic disorders]. / Krótkowzrocznosc w schorzeniach ogólnoustrojowych.

Myopia is the most common refractive error Myopia has been well established as a multifactorial disease with both genetic and environmental etiology. A number of genetic loci have been linked with myopia. We have described the prevalence and the symptoms of systemic disorders associated with myopia, including: Stickler syndrome, Marfan syndrome, Ehlers-Danlos syndrome, Weill-Marchesani syndrome, homocystinuria, McCune-Albright syndrome, Kniest syndrome, Down syndrome, Prader-Willi syndrome, Noonan syndrome, Cohen syndrome, Rubinstein-Taybi syndrome, Cornelia de Lange syndrome and fetal alcohol syndrome.

Submicroscopic deletion of chromosome region 16p13.3 in a Japanese patient with Rubinstein-Taybi syndrome.

In a series of 25 Japanese patients with Rubinstein-Taybi syndrome, we screened, by high-resolution GTG banding and fluorescence in situ hybridization of a cosmid probe (RT1, D16S237), for microdeletions associated with this syndrome. In one patient, a microdeletion was demonstrated by in situ hybridization, but none were detected by high-resolution banding.

Broad thumb-hallux (Rubinstein-Taybi) syndrome 1957-1988.

This presentation records the early history of the description of the broad thumb-hallux syndrome and attempts to update the current state of knowledge about this syndrome. Information was collected and reviewed on 571 individuals from the world literature, from communications with colleagues and families of affected individuals, and from personal observation. The diagnosis was established in most cases by confirming the concurrence of the constellation of major diagnostic criteria, including broad short terminal phalanges of the thumbs and halluces, with or without angulation deformity; characteristic facial appearance with beaked or straight nose, antimongoloid slant of palpebral fissures, apparent or clinical hypertelorism and grimacing smile; stature and head circumference (OFC) below 50th centile; mental, motor, social, and language retardation; stiff awkward gait; and incomplete or delayed descent of testes in males. Information on associated clinical factors, familial occurrence, and cytogenetic findings is presented.

Etiology and recurrence risk in Rubinstein-Taybi syndrome.

Epidemiologic data on 45 patients with Rubinstein-Taybi syndrome from the Netherlands and 50 patients from the USA are compared with data from 407 patients reported in the literature. The 502 probands had a total of 708 sibs, including one probable recurrence. In 12 of 13 proven or possible monozygotic twins both children were affected. Two patients have reproduced with one affected and 2 normal offspring. The empiric recurrence risk figure for sibs is 0.1%. The recurrence risk for offspring of affected individuals could be as high as 50%. The cause of the syndrome remains unknown. There were no clues for autosomal recessive or X-linked inheritance, nor for a teratogenic cause. No consistent chromosome anomaly was found. An autosomal dominant mutation, either as submicroscopic chromosome deletion or duplication, or a point mutation seems the most likely explanation.