Diagnosis Of Rubinstein-Taybi Syndrome Research Articles

Anesthetic Considerations in a Child with Rubinstein–Taybi Syndrome

Rubinstein − Taybi Syndrome (RTS) is a rare genetic syndrome caused by a mutation in the cAMP response element binding protein gene or EP300 gene or as the result of microdeletion from short (p) arm of chromosome 16. The diagnosis of RTS is made primarily through physical appearance. It may be associated with the disorders of multiple organ systems. Anesthetic management might be challenging in RTS due to various factors. A thorough preoperative evaluation and careful preparation for difficult airways before anesthesia is mandatory for successful case management. Here, we report the case of a 9-year-old child with RTS posted for cystoscopy.

Синдром Рубінштейна-Тейбі в неонатальній практиці (випадок із практики)

The article presents data on a rare genetic disease - Rubinstein-Taybi syndrome. The disease incidence is 1: 25000-1: 30000. Parents’ lifestyle has no influence on the birth of a child with Rubinstein-Taybi syndrome. The risk of having a second child with the same pathology is 0.1%. The syndrome is characterized by the presence of deformed digits, distinctive facial features and mental retardation. Clinical signs of the disease occur as a result of mutation in the gene encoding a specific GreB protein. This gene is localized on the chromosome 16. The article reports on the main phenotypic deviations and analyzes the literature data on somatic and neurological pathologies. The syndrome is characterized by a combination of delayed physical and psychomotor development, progressive intellectual disability, characteristic craniofacial dysmorphism, deformity of digits (namely broad, short and wide distal phalanges of the thumbs and big toes, sometimes distal phalanges of other fingers and toes), abnormalities of the cardiovascular, respiratory and urogenital systems. The article presents primary data on the diagnosis of Rubinstein-Taybi syndrome in a child of neonatal age. The boy’s parents, young people, and the newborn’s sister, aged 3, are healthy. No phenotypic manifestations of skeletal dysplasia were detected. The relatives’ hereditary history is negative. We have observed the following facial dysmorphia: low forehead, low hair growth line, high-arched eyebrows, moon-shaped face, hypertelorism, downward slanted eyes, «beaked» nose, hypoplastic nasal wings, moderate retrognathia, high narrow palate, dysplastic, small, low-lying auricles. Broad terminal phalanges of thumbs and big toes, as well as valgus deformity of the thumbs were observed. The child was diagnosed with an open aortic duct and congenital choanal atresia on the right. Thus, a severe disabling pathology in a child born to apparently healthy parents indicates a sporadic de novo mutation. The research was carried out in accordance with the principles of the Helsinki declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors. Key words: Rubinstein-Taybi syndrome, craniofacial abnormalities, digit abnormalities, newborns.

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.

CREBBP gene mutation in two boys with Rubinstein-Taybi syndrome

To investigate the clinical and genetic features of 2 patients with Rubinstein-Taybi syndrome. Using next generation sequencing (NGS) the CREBBP and EP300 genes of 2 children who were diagnosed as Rubinstein-Taybi syndrome at Peking Union Medical College Hospital. The mutations identified by NGS were verified by PCR were analyzed. The 2 patients at the age of 5 months and 4.5 years manifested short stature (the height were 60 cm and 99 cm respectively), low hairline, thick and dense hair and eyebrows, long lash, epicanthus of both eyes, protruded supercilliary arch, broad and flat thumbs and halluces, and particular facial abnormalities. Patient 2 had language retardation besides. One missense mutation of c.3535A>G, p.Ser1179Gly was found in CREBBP gene in patient 1 and one microdeletion mutation of c.4995_4999delCGCCT, p. Ala1666Pro fs66x was found inpatient 2. Both mutations were reported for the first time. Rubinstein-Taybi syndrome is characterized by mental and growth retardation, wide and flat thumbs and first toes, and dysmorphic facial features. CREBBP is one of the causative genes. Mutation detection on CREBBP gene can confirm the diagnosis of Rubinstein-Taybi syndrome.

Rubinstein-Taybi syndrome: Dental manifestations and management

Rubinstein-Taybi syndrome (RSTS) is an uncommon genetic disorder characterised by a typical facies, small stature, broad angulated thumbs and intellectual impairment. Dental changes are a minor, yet significant component of the condition. Craniofacial growth retardation in RSTS is frequently complicated by unerupted teeth, while dental caries is related to the inherent intellectual deficit. Dental problems necessitate interdisciplinary management in terms of oral surgery, conservative dentistry, periodontics and orthodontics. When affected individuals are unco-operative, certain dental procedures may warrant general anaesthesia. In these instances, dental and medical staff will combine their expertise to enhance the well-being of the patient. In addition, specific dental changes may alert the medical practitioner to the possible diagnosis of RSTS. In this article we document the oro-dental manifestations and review the oro-dental approach in the management of three patients with RSTS. Our experience in South Africa may be relevant to other countries at a similar stage of development.

Exome sequencing identifies a novelEP300frame shift mutation in a patient with features that overlap cornelia de lange syndrome

Rubinstein-Taybi syndrome (RTS) and Cornelia de Lange syndrome (CdLS) are genetically heterogeneous multiple anomalies syndromes, each having a distinctive facial gestalt. Two genes (CREBBP and EP300) are known to cause RTS, and five (NIPBL, SMC1A, SMC3, RAD21, and HDAC8) have been associated with CdLS. A diagnosis of RTS or CdLS is molecularly confirmed in only 65% of clinically identified cases, suggesting that additional causative genes exist for both conditions. In addition, although EP300 and CREBBP encode homologous proteins and perform similar functions, only eight EP300 positive RTS patients have been reported, suggesting that patients with EP300 mutations might be escaping clinical recognition. We report on a child with multiple congenital abnormalities and intellectual disability whose facial features and complex phenotype resemble CdLS. However, no mutations in CdLS-related genes were identified. Rather, a novel EP300 mutation was found on whole exome sequencing. Possible links between EP300 and genes causing CdLS are evident in the literature. Both EP300 and HDAC8 are involved in the regulation of TP53 transcriptional activity. In addition, p300 and other chromatin associated proteins, including NIPBL, SMCA1, and SMC3, have been found at enhancer regions in different cell types. It is therefore possible that EP300 and CdLS-related genes are involved in additional shared pathways, producing overlapping phenotypes. As whole exome sequencing becomes more widely utilized, the diverse phenotypes associated with EP300 mutations should be better understood. In the meantime, testing for EP300 mutations in those with features of CdLS may be warranted.

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.

Overlap between Rubinstein-Taybi and Saethre-Chotzen syndromes: A case report

This report concerns a 14-year follow-up of a patient whose clinical manifestations led to a diagnosis of Rubinstein-Taybi syndrome; however, his intelligence is normal. Reappraisal resulted in a change of diagnosis to Saethre-Chotzen syndrome. Overlapping manifestations in the 2 syndromes are discussed.