ABSTRACT
OBJECTIVE@#To explore the clinical characteristics and genetic etiology of a child with Rubinstein-Taybi syndrome (RSTS).@*METHODS@#A child who was admitted to the Children's Hospital of Soochow University on October 3, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected. The child was subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing of his family members and bioinformatic analysis.@*RESULTS@#The patient, a 9-year-and-４-month-old boy, had manifested unique facies, microcephaly, broad toes, growth retardation, and intellectual impairment. WES revealed that he has harbored a heterozygous c.3604G>T (p.E1202*) variant in exon 20 of the EP300 gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. The variant was not found in the Shenzhou Genome data Cloud, ExAC, 1000 Genomes and gnomAD databases．Analysis with SIFT, PolyPhen-2 and CADD online software has predicted the variant to be harmful. Based on the guidelines formulated by the American College of Medical Genetics and Genomics, the variant was rated as pathogenic (PVS1＋PS2＋PM2_Supporting) .@*CONCLUSION@#The heterozygous c.3604G>T variant of the EP300 gene probably underlay the RSTS type 2 in this child. Above finding has also expanded the variation spectrum of the EP300 gene.
Subject(s)
Child , Humans , Male , Computational Biology , E1A-Associated p300 Protein/genetics , Exons , Face , Facies , Rubinstein-Taybi Syndrome/geneticsABSTRACT
Introducción: El síndrome de Rubinstein Taybi es una patología de origen genético que afecta a 1 de cada 100.000 a 125.000 nacidos vivos, se caracteriza por presentar: retraso en el crecimiento, retraso en el desarrollo psicomotriz y anomalías morfológicas que incluyen: rasgos faciales peculiares (cejas arqueadas y gruesas, fisuras palpebrales inclinadas hacia abajo, puente nasal convexo con punta de la nariz por debajo de las alas), pulgares y hallux anchos. Su origen epigenético en el 60% de los casos se debe a una alteración en el gen CREBBP (codificador de la proteína CPB), en el 10% a un cambio en el gen EP300 (codificador de la proteína p300) y en el 30% no se han logrado identificar su causa. Caso clínico: Niño de 8 años de edad con retardo en el desarrollo psicomotriz, con dificultades para la adaptación escolar. Al examen físico con rasgos faciales: cejas superpobladas y arqueadas, hirsutismo en frente y región de labio superior, fisuras palpebrales inclinadas hacia abajo, hipertelorismo con estrabismo convergente, puente nasal ancho, nariz achatada, la punta se extiende levemente por debajo de las alas nasales. Con hirsutismo en región cervical e interescapular. En las manos se identifica dedos pulgares anchos, en el resto de dedos se evidencian falanges distales ensanchadas, de igual forma en la región de los pies se identifican hallux anchos y falanges distales ensanchadas. Evolución: El paciente sigue en observación por consulta externa, fue enviado a programas de terapia de lenguaje, lectura y psicomotriz. No ha desarrollado infecciones pulmonares hasta el cierre del seguimiento, 6 meses posteriores al diagnóstico. Conclusión: En presente caso reporta las alteraciones fenotípicas características faciales y de extremidades de un niño con síndrome de Rubinstein-Taybi, las cuales ayudaron al diagnóstico clínico.
Introduction: Rubinstein-Taybi syndrome is a pathology of genetic origin that affects 1 out of every 100,000 to 125,000 live births, it is characterized by: growth retardation, delay in psy-chomotor development and morphological abnormalities that include: peculiar facial features (thick arched eyebrows, downward sloping palpebral fissures, convex nasal bridge with tip of nose below wings), broad thumbs and hallux. Its epigenetic origin in 60% of cases is due to an alteration in the CREBBP gene (coding for CPB protein), in 10% to a change in the EP300 gene (coding for p300 protein) and in the 30% have not been able to identify its cause. Clinical case: 8-year-old boy with a delay in psychomotor development, with difficulties in adapting to school. On physical examination with facial features: overpopulated and arched eyebrows, hirsutism in the forehead and upper lip region, downward sloping palpebral fissures, hypertelorism with convergent strabismus, wide nasal bridge, flattened nose, the tip extends slightly below the nasal wings. With hirsutism in the cervical and interscapular region. In the hands, broad thumbs are identified, in the rest of the fingers there are widened distal phalanges, in the same way in the region of the feet, wide hallux and widened distal phalanges are identified. Evolution: The patient continues to be observed by outpatient consultation, he was sent to speech, reading and psychomotor therapy programs. He has not developed pulmonary infections until the close of follow-up, 6 months after diagnosis. Conclusion: In this case, it reports the phenotypic alterations of the facial and limb characteristics of a child with Rubinstein-Taybi syndrome, which helped the clinical diagnosis.
Introdução: A síndrome de Rubinstein-Taybi é uma patologia de origem genética que afeta 1 em cada 100.000 a 125.000 nascidos vivos, é caracterizada por: retardo de crescimento, atraso no desenvolvimento psicomotor e anormalidades morfológicas que incluem: características faciais peculiares (sobrancelhas arqueadas e grossas, descendente fissuras palpebrais, ponte nasal convexa com a ponta do nariz abaixo das asas), polegares largos e hálux. Sua origem epigenética em 60% dos casos deve-se a uma alteração no gene CREBBP (que codifica a proteína CPB), em 10% a uma alteração no gene EP300 (que codifica a proteína p300) e em 30% sua causa não foi identificada . Caso clínico: Menino de 8 anos com atraso no desenvolvimento psicomotor, com dificuldade de adaptação à escola. No exame físico com características faciais: sobrancelhas superpovoadas e arqueadas, hirsutismo na testa e região do lábio superior, fissuras palpebrais inclinadas para baixo, hipertelorismo com estrabismo convergente, ponte nasal larga, nariz achatado, a ponta se estende ligeiramente abaixo das asas nasais. Com hirsutismo na região cervical e interescapular. Nas mãos identificam-se os polegares largos, nos restantes dedos são identificadas falanges distais alargadas, da mesma forma que na região dos pés, hálux largo e falanges distais alargadas. Evolução: O paciente ainda está em acompanhamento ambulatorial, foi encaminhado para programas de fonoaudiologia. Ele não desenvolveu infecções pulmonares até o fechamento do acompanhamento, 6 meses após o diagnóstico. Conclusão: Nesse caso, relata as alterações fenotípicas das características faciais e de membros de uma criança com síndrome de Rubinstein-Taybi, o que auxiliou no diagnóstico clínico.
Subject(s)
Humans , Child , Rubinstein-Taybi Syndrome , Case Reports , Thumb , Craniofacial Abnormalities , Chromosome DisordersABSTRACT
OBJETIVO: Analisar o comportamento motor de uma criança com Síndrome de RubinsteinTaybi sob estimulação fisioterapêutica. MÉTODO: Trata-se de um estudo de caso realizado com uma criança diagnosticada com SRT avaliada antes, durante e após sessões de fisioterapia através da Alberta Infant Motor Scale. O tratamento foi realizado no Centro de Integração Raio de Sol, em Aracaju/SE, onde as condutas foram aplicadas três vezes na semana, com duração de 50 minutos, e consistiram no treino das posturas neuroevolutivas. RESULTADOS: Verificou-se aumento nos escores de todas as posturas a partir da segunda avaliação, o que demonstra melhora no desenvolvimento motor. CONCLUSÃO: A intervenção fisioterapêutica pode trazer benefícios no tratamento do atraso característico da SRT, ratificando a importância de novos estudos que investiguem o desempenho motor e o efeito da estimulação precoce em crianças com essa síndrome.
OBJECTIVE: Analyze the motor behavior of a child with Rubinstein-Taybi Syndrome under physical therapy stimulation. METHOD: This is a case study realized with a child diagnosed with SRT, evaluated before, during, and after physiotherapy sessions, through the Alberta Infant Motor Scale. The treatment was fulfilled at the Sun Ray Integration Center located in the Santa Maria neighborhood, in Aracaju / SE in which the ducts were applied three times a week for 50 minutes and consisted in the training of neuroevolutionary postures. RESULTS: It was verified an increase in all postures scores in the second and third evaluations, which shows an improvement in motor development. CONCLUSION: The Physiotherapeutic intervention can bring benefits to treat the characteristic delay of SRT, confirming the importance of further studies investigating motor performance and the effect of early stimulation in children with this syndrome.
Subject(s)
Rubinstein-Taybi Syndrome , Child Health , Physical Therapy ModalitiesABSTRACT
Abstract Pilomatricomas are benign tumors originating from the capillary matrix, which may present as solitary lesions or, less commonly, multiple. Myotonic dystrophy and familial adenomatous polyposis are the most frequently associated disorders with multiple pilomatricomas. There are few reports relating these tumors to other genetic syndromes. Rubinstein-Taybi syndrome is a rare autosomal dominant disorder characterized by intellectual disability and typical dysmorphic characteristics. There are five case reports relating to multiple pilomatricoma to Rubinstein-Taybi syndrome, an association that needs to be clarified. For this reason, we report the first case of multiple pilomatricoma in monozygotic twins with typical Rubinstein-Taybi syndrome.
Subject(s)
Humans , Rubinstein-Taybi Syndrome , Skin Neoplasms , Pilomatrixoma/blood , Hair DiseasesABSTRACT
El síndrome de Rubinstein-Taybi (SRT) es una rara anomalía congénita, de etiología todavía incierta. Su incidencia es de 1:100 000 a 1:300 000 nacimientos. El objetivo de este reporte de caso fue describir los hallazgos orofaciales y el acompañamiento dental por 7 años de un paciente del sexo masculino diagnosticado como portador del SRT. Las principales características orofaciales observadas fueron: mirada antimongoloide, "nariz en pico", orejas grandes y de baja inserción, estatura corta, gran cantidad de cabello, pequeña abertura de boca, queilitis angular, paladar estrecho y profundo, apiñamiento dental, mordida cruzada posterior bilateral, hipomineralización de molares primarios (HMP), hipomineralización de molares e incisivos (HMI), mala higiene oral, presencia de cálculos supragingival, gingivitis y gran número de lesiones de caries activas. El SRT muestra muchas manifestaciones orofaciales y su conocimiento puede ayudar en el diagnóstico y tratamiento temprano. Las consultas odontológicas a intervalos más cortos ayudan a acondicionar al paciente y reducen el riesgo de lesiones de caries y problemas gingivales.
A síndrome de Rubinstein-Taybi (SRT) é uma anomalia congênita rara, de etiologia ainda incerta. Sua incidência é de 1:100.000 a 300.000 nascimentos. O objetivo deste relato de caso foi descrever os achados orofaciais e o acompanhamento odontológico por 7 anos de um paciente do sexo masculino diagnosticado como portador da SRT. As principais características orofaciais observadas foram: olhar antimongolóide, "nariz em bico", orelhas grandes e de baixa inserção, baixa estatura, grande quantidade de cabelo, pequena abertura bucal, queilite angular, palato estreito e profundo, apinhamento dentário, mordida cruzada posterior bilateral, hipomineralização de molares decíduos (HMD), hipomineralização molar-incisivo (HMI), higiene bucal deficiente, presença de cálculos supra-gengivais, gengivite e grande número de lesões de cárie ativas. A SRT apresenta muitas manifestações orofaciais e seu conhecimento pode ajudar no diagnóstico e tratamento precoce. Consultas odontológicas em menores intervalos de tempo ajudam no condicionamento do paciente e reduzem o risco de lesões de cárie e problemas gengivais
Rubinstein-Taybi syndrome (RTS) is a rare congenital anomaly of uncertain etiology. Its incidence ranges from 1:100,000 to 300,000 births. The objective of this case report was to describe the orofacial findings and a 7-year follow-up of a male patient diagnosed with RTS. The main orofacial features observed include: antimongoloid slant, beaked nose, low set large ears, short stature, large amount of hair, limited mouth opening, angular cheilitis, narrow and deep palate, dental crowding, bilateral posterior crossbite, deciduous molar hypomineralization (DMH), molar incisor hypomineralization (MIH), poor oral hygiene, presence of supra-gingival calculi, gingivitis and a large number of active carious lesions. RTS has many orofacial manifestations and knowledge of this syndrome can help in proper diagnosis and early treatment. Dental appointments at shorter time intervals help in conditioning the patient and reduce the risk of caries lesions and periodontal problems.
Subject(s)
Humans , Male , Child , Rubinstein-Taybi Syndrome , Palate , Congenital Abnormalities , Therapeutics , Dental OfficesABSTRACT
OBJECTIVE@#To summarize the clinical characteristics and identify gene mutations of 2 probands with Rubinstein-Taybi syndrome (RSTS).@*METHODS@#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.@*RESULTS@#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.@*CONCLUSION@#Two cases of Rubinstein-Taybi syndrome were diagnosed, which facilitated the diagnosis and genetic counselling.
Subject(s)
Humans , CREB-Binding Protein , Genetics , Genetic Testing , High-Throughput Nucleotide Sequencing , Phenotype , Rubinstein-Taybi Syndrome , GeneticsABSTRACT
The patient was a girl aged 3 years and 8 months with normal body length and body weight at birth. The girl had feeding difficulty after birth. Her height, body weight, and head circumference were below the 3rd percentile. She had intellectual disability and an unusual facies manifesting as arched shaggy eyebrows, down-slanting palpebral fissures, and broad nasal bridge, but had no a beaked nose, broad thumbs, or big toes. These clinical manifestations were basically consistent with Rubinstein-Taybi syndrome (RSTS). Gene sequencing identified a heterozygous splice site mutation, c.3779T+1G>T, in the CREBBP gene, which did not exist in her parents. Therefore, a definite diagnosis of RSTS was made. The mutation c.3779T+1G>T had not been reported in the Human Gene Mutation Database and was identified as a novel pathogenic mutation. Then the girl was given rehabilitation training for delayed language and motor development. The girl has been followed up for 3 months in the outpatient department, but the effect of rehabilitation treatment has not been evaluated.
Subject(s)
Child, Preschool , Female , Humans , CREB-Binding Protein , Genetics , Mutation , Rubinstein-Taybi Syndrome , Genetics , RehabilitationABSTRACT
Rubinstein-Taybi syndrome (RTS) is a rare autosomal dominant disorder characterized by mental and growth retardation, craniofacial, vertebral, ocular and cardiac anomalies, gastro-esophageal reflux, and difficult airway management. Patients with this syndrome can also experience upper airway obstruction during sleep, which is caused by hypotonia and the abnormal anatomy of the oropharynx and airways, and become susceptible to obstructive sleep apnea. In our case, respiratory arrest developed in an RTS patient who had undergone Tonsillectomy and Adenoidectomy (T&A) surgery. It is the first report of respiratory arrest after T&A surgery in a young child with RTS.
Subject(s)
Child , Humans , Adenoidectomy , Airway Management , Airway Obstruction , Gastroesophageal Reflux , Muscle Hypotonia , Oropharynx , Rubinstein-Taybi Syndrome , Sleep Apnea Syndromes , Sleep Apnea, Obstructive , TonsillectomySubject(s)
Adult , Humans , Male , Hallux/pathology , Rubinstein-Taybi Syndrome/diagnosis , Thumb/pathologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the clinical and genetic features of 2 patients with Rubinstein-Taybi syndrome.</p><p><b>METHOD</b>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.</p><p><b>RESULT</b>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.</p><p><b>CONCLUSION</b>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.</p>
Subject(s)
Child , Humans , Male , CREB-Binding Protein , Genetics , High-Throughput Nucleotide Sequencing , Mutation , Genetics , Mutation, Missense , Rubinstein-Taybi Syndrome , Diagnosis , GeneticsSubject(s)
Humans , Female , Child , Hypertrichosis , Rubinstein-Taybi Syndrome , Head , Lower ExtremityABSTRACT
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.
Subject(s)
Adolescent , Child , Child, Preschool , Craniofacial Abnormalities/epidemiology , Craniofacial Abnormalities/etiology , Early Diagnosis , Humans , Infant , Infant, Newborn , Intellectual Disability/epidemiology , Intellectual Disability/etiology , Intelligence/classification , Rubinstein-Taybi Syndrome/diagnosis , Rubinstein-Taybi Syndrome/epidemiology , Rubinstein-Taybi Syndrome/etiology , Rubinstein-Taybi Syndrome/therapyABSTRACT
Rubinstein-Taybi syndrome (RTS) is characterized by peculiar facies, mental retardation, broad thumbs, and great toes. Approximately one-third of the affected individuals have a variety of congenital heart diseases. They can also have upper airway obstruction during sleep, due to hypotonia and the anatomy of the oropharynx and airway, which make these patients susceptible to obstructive sleep apnea (OSA). In our case, pulmonary hypertension was caused, successively, by congenital heart defects (a large patent ductus arteriosus and arch hypoplasia) and obstructive sleep apnea during early infancy. The congenital heart defects were surgically corrected, but persistent pulmonary hypertension was identified 2 months after the operation. This pulmonary hypertension was due to OSA, and it was relieved by nasal continuous positive airway pressure. This case is the first report of pulmonary hypertension from OSA in a young infant with RTS.
Subject(s)
Child , Humans , Infant , Airway Obstruction , Continuous Positive Airway Pressure , Ductus Arteriosus, Patent , Facies , Heart Defects, Congenital , Heart Diseases , Hypertension, Pulmonary , Intellectual Disability , Muscle Hypotonia , Oropharynx , Rubinstein-Taybi Syndrome , Sleep Apnea, Obstructive , Thumb , ToesABSTRACT
Rubinstein-Taybi syndrome (RTS) is characterized by peculiar facies, mental retardation, broad thumbs, and great toes. Approximately one-third of the affected individuals have a variety of congenital heart diseases. They can also have upper airway obstruction during sleep, due to hypotonia and the anatomy of the oropharynx and airway, which make these patients susceptible to obstructive sleep apnea (OSA). In our case, pulmonary hypertension was caused, successively, by congenital heart defects (a large patent ductus arteriosus and arch hypoplasia) and obstructive sleep apnea during early infancy. The congenital heart defects were surgically corrected, but persistent pulmonary hypertension was identified 2 months after the operation. This pulmonary hypertension was due to OSA, and it was relieved by nasal continuous positive airway pressure. This case is the first report of pulmonary hypertension from OSA in a young infant with RTS.
Subject(s)
Child , Humans , Infant , Airway Obstruction , Continuous Positive Airway Pressure , Ductus Arteriosus, Patent , Facies , Heart Defects, Congenital , Heart Diseases , Hypertension, Pulmonary , Intellectual Disability , Muscle Hypotonia , Oropharynx , Rubinstein-Taybi Syndrome , Sleep Apnea, Obstructive , Thumb , ToesABSTRACT
Rubinstein-Taybi Syndrome is a rare genetic disorder with characteristic features including downward slanting palpebral fissures, broad thumbs and halluces, and mental retardation. Systemic features may involve cardiac, auditory, ophthalmic, endocrine, nervous, renal and respiratory systems. This syndromeis sporadic in nature and has been linked to microdeletion at 16p 13.3 encoding CREB-binding protein gene [CREBBP]. We report a 15-years-old girl, a known case of chronic renal failure, with downward slanting palpebral fissures towardthe ears, hypertelorism, short stature, beaked nose, micrognathia, strabismus, dental anomalies, large toes, broad thumbs, and mental retardation
Subject(s)
Humans , Female , Intellectual Disability , Chromosomes, Human, Pair 16 , Chromosome Deletion , CREB-Binding Protein , Rubinstein-Taybi Syndrome/geneticsABSTRACT
PURPOSE: The authors report a case of Rubinstein-Taybi syndrome with optic disc coloboma and chorioretinal coloboma. CASE SUMMARY: A 17-month-old female infant was brought to our clinic presenting exodeviation in the right eye. On cycloplegic refraction, her refractive power was -5.50 D sph -2.50 D cyl axis 180degrees in the right eye and +0.50 D sph in the left eye. On ophthalmologic examination, exotropia of 60 prism diopters with no limitation of ocular movement was observed. Fundus examination showed optic disc coloboma and chorioretinal coloboma in the right eye. The patient's physical characteristics were downward slanted palpebral fissures, long eyelashes, low set ears, and the thumb and the big toe were disproportionately broad. The patient also demonstrated delayed gait abilities. The clinical diagnosis of Rubinstein-Taybi syndrome was given. CONCLUSIONS: The authors report a child with Rubinstein-Taybi syndrome with optic disc coloboma and chorioretinal coloboma, the first to be reported in Korea.