The relationship between neurodevelopmental transcriptional programs and insomnia: From Rubinstein-Taybi syndrome into energy metabolism.

Neurodevelopmental disorders (NDD) are characterized by cognitive, emotional, and/or motor skills impairment since childhood, and sleep disturbances are a common comorbidity. Rubinstein-Taybi syndrome (RSTS), a rare genetic syndrome associated with NDD, is caused by CREBBP haploinsufficiency. This gene encodes an acetyltransferase with crucial role on the establishment of transcriptional programs during neurodevelopment. Although insomnia has been reported in RSTS patients, the convergent mechanisms between this sleep disturbance and CREBBP loss-of-function are not fully understood. We tested weather the genetic architecture underlying CREBBP regulatory targets and insomnia-associated genes is significantly shared. We then identified the biological pathways enriched among these shared genes. The intersection between CREBBP regulatory targets and genes associated with insomnia included 7 overlapping genes, indicating significantly more overlap than expected by chance. An over-representation analysis on these intersect genes identified pathways related to mitochondrial activity. This finding indicates that the transcriptional programs established by CREBBP might impact insomnia-related biological pathways through the modulation of energy metabolism. The overlapping gene set and biological pathways highlighted by this study may serve as a primer for new functional investigations of shared molecular mechanisms between insomnia and CREBBP regulatory targets.

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.

Multiplex ligation-dependent probe amplification detection of an unknown large deletion of the CREB-binding protein gene in a patient with Rubinstein-Taybi syndrome.

Rubinstein-Taybi syndrome is a rare autosomal dominant congenital disorder characterized by postnatal growth retardation, psychomotor developmental delay, skeletal anomalies, peculiar facial morphology, and tumorigenesis. Mutations in the gene encoding the cAMP response element-binding protein (CREB, also known as CREBBP or CBP) on chromosome 16p13.3 have been identified. In addition, some patients with low intelligence quotients and autistic features bear large deletions. Based on these observations, we used multiplex ligation-dependent probe amplification to search for large deletions affecting the CREBBP gene in a Rubinstein-Taybi syndrome patient. We identified a novel heterozygote deletion removing five exons (exons 17-21), encoding the histone acetyltransferase domain. We propose the use of multiplex ligation-dependent probe amplification as a fast, accurate and cheap test for detecting large deletions in the CREBBP gene in the sub-group of Rubinstein-Taybi syndrome patients with low intelligence quotients and autistic features.

Dental management of a patient with Rubinstein-Taybi syndrome.

Rubinstein-Taybi syndrome (RTS) occurs in one out of 300,000 individuals. It is mainly characterized by a delay in growth, psychomotor retardation, duplication of the distal phalanx of the thumbs, typical facial dimorphism, a risk of cancer, and multiple dental abnormalities. This case report describes the dental management of a 13-year-old female with RTS, who had multiple dental problems such as caries, periodontal disease, and a severe malocclusion. Physical findings were similar to those previously described in other reports. Dental treatment was carried out under sedation due to the patient's inability to cooperate during dental treatment. After 3 years of follow-up there were no new caries and the periodontal health had improved.

Principais características das cicatrizes queloideanas / Brief accout of the clinical and histological features of keloids, their treatment

Breve relato das características clínicas e histológicas dos quelóides, sua diferenciaçäo das cicatrizes hipertróficas e os vários métodos de tratamento

[Rubinstein-Taybi syndrome. Report of 2 cases]. / Sindrome de Rubinstein-Taybi. Relato de dois casos

Two non-inbred cases of Rubinstein-Taybi syndrome is two non-related sibships with a total of 16 sibs are reported. Clinical features are those classicaly reported. One of the patients (case 1) presents left post-axial polydactily and a history of hydramnion. The cariotype is normal in the other patient (case 2). Nothing is added in this paper as regards the etiology of the syndrome.