Última actualización:
7/20/2023
Años publicados: 1987, 1989, 1992, 1997, 1998, 2002, 2004, 2015, 2018, 2023
NORD gratefully acknowledges Annie Sescleifer, NORD Editorial Intern from the University of Notre Dame, and Cathy A. Stevens, MD, FACMG, Professor of Pediatrics, Director of Medical Genetics, University of Tennessee, Children’s Hospital at Erlanger, for assistance in the preparation of this report.
Rubinstein-Taybi syndrome (RSTS) is a rare genetic disorder that affects many organ systems. RSTS is characterized by growth delays, distinctive facial features, intellectual disability (with an average IQ of 25-79), broad and often angulated thumbs and great toes (halluces) and feeding difficulties (dysphagia). Craniofacial features of RSTS include downward slanted eyes (down slanted palpebral fissures), long eyelashes, high-arched eyebrows, low-hanging nasal septum (columella), high palate and an extra cusp on the lingual side of a front tooth (talon cusps). In most affected children, RSTS occurs as the result of a new (de novo) gene variant (mutation), although rarely, the syndrome has been inherited from an affected parent in an autosomal dominant pattern. Management generally involves monitoring of growth and feeding, yearly eye and hearing evaluations, and evaluation for cardiac, dental, and renal abnormalities. Behavioral therapy and special education are also indicated.
General
RSTS is a rare genetic disorder which may affect many organ systems of the body. Features include distinctively broad and/or angled fingers and toes, developmental delays, short stature, speech delays, intellectual disability, characteristic appearance of the head and face (craniofacial dysmorphism), breathing and feeding difficulties (dysphagia) and urogenital abnormalities. In some people, the skin, heart and/or respiratory system may also be affected. Symptoms associated with RSTS vary greatly from person to person.
Most infants with RSTS have thumbs and/or great toes that are broad because of unusual broadness of the bones in the tips of the thumbs and great toes (terminal phalanges). In addition, the distal bones of the thumbs and great toes may be angled improperly (misaligned) on a proximal bone that is abnormally shaped (delta phalanx). The fifth fingers may be curved inward (clinodactyly). Individuals with RSTS with EP300 gene variants (mutations) have fewer characteristic facial and extremity findings and milder developmental impairment than people with CREBBP gene variants.
Growth and Development
While prenatal growth is often normal, in most infants with RSTS, parameters for height, weight and head circumference fall below the fifth percentile during infancy. Affected infants fail to grow and gain weight at the expected rate (failure to thrive). Although weight gain can be very slow in infancy, children with RSTS may later show a relative obesity for their height. Feeding difficulties (dysphagia) may occur and many affected individuals are prone to repeated respiratory infections. As children age, they may continue to experience poor growth and exhibit short stature (most below the third percentile).
Most infants and children with RSTS have varying degrees of intellectual disability (average IQ between 25-79), delays in the acquisition of skills requiring coordination of muscular and mental activities (psychomotor delays) and delayed socialization. Most affected infants and children do not reach certain developmental milestones (e.g., sitting, crawling, standing, walking, etc.) at a time when they would otherwise be expected. Most children with RSTS experience a significant delay in expressive speech. In addition, there may be diminished muscle tone (hypotonia), abnormally exaggerated reflexes (hyperreflexia) and a stiff, unsteady gait.
Physical Features
Infants with RSTS have several distinctive head and facial (craniofacial) features. Most affected infants have a “beak-shaped” or straight nose with a broad nasal bridge. Typically, there are down slanting eyelid openings (palpebral fissures) and the wall (septum) dividing the nostrils may extend below the nostrils (low hanging columella). Children with RSTS typically have a small head (microcephaly), below the 5th percentile.
Characteristic features of the mouth and jaw may be present including a small mouth, short, thin upper lip, highly arched roof of the mouth (palate), underdeveloped upper jawbone (maxilla) and a small lower jaw (micrognathia) that is displaced farther back than otherwise expected (retrognathia). Many affected infants have irregularly shaped, crowded teeth, resulting in upper and lower jaws that do not meet properly (malocclusion). Affected individuals may have a boney protuberance on the lingual aspect of the upper front teeth (talon cusps). The soft tissue structure that hangs in the back of the throat may also be divided (bifid uvula). In addition, some affected individuals may appear to be frowning or upset when they smile.
In addition to broad thumbs and toes, some children with RSTS may have toes that overlap or unusually shaped bones of the feet (metatarsals).
Affected individuals may have overgrowth of scar tissue at the site of a cut, injury, or surgical incision (keloid formation) or this may occur spontaneously.
Eyes
Affected infants have specific characteristics of the eyes including eyes that appear widely spaced (apparent hypertelorism); crossed eyes (strabismus); upper eyelids that droop (ptosis) and/or extra folds of skin on either side of the nose that may cover the eyes’ inner corners (epicanthal folds).
Skeletal Abnormalities
There may be additional skeletal characteristics including side-to-side (scoliosis) or front-to-back (kyphosis) curvature of the spine, depression of the bone forming the center of the chest (sternum), known as “funnel chest” or pectus excavatum, abnormalities of vertebrae and the pelvis, malformations of ribs, and recurrent dislocation of the kneecaps. The lower end of the spinal cord may be abnormally tied down (tethering).
Genitourinary Tract
Male infants with RSTS have abnormalities of the genitourinary tract including failure of one or both testes to descend into the scrotum (cryptorchidism), a fold of skin extending around the base of the penis (shawl scrotum) and/or misplacement of the urinary opening, such as on the underside of the penis (hypospadias). In addition, infants with RSTS may have underdeveloped (hypoplastic) or absent kidney(s), repeated infections of the urinary tract, kidney stones, unusual accumulation of urine in the kidney (hydronephrosis) and/or backflow (reflux) of urine into the tubes (ureters) that normally bring urine to the bladder. In some cases, duplication of the kidneys and/or ureters may also be present.
Cardiac
Approximately one third of infants with RSTS have an associated heart defect that is present at birth (congenital heart defect). According to the medical literature, patent ductus arteriosus may be the most common congenital heart defect present in infants with RSTS. Infants with RSTS may also have extra heart sounds (heart murmurs), narrowing of the opening between the pulmonary artery and the right ventricle of the heart (pulmonary stenosis), narrowing of the aorta (aortic coarctation) and/or ventricular septal defects (VSDs) and/or atrial septal defects (ASDs). The symptoms associated with a ventricular septal defect or atrial septal defect vary from person to person, depending upon the size and location of the defect.
Respiratory
Affected individuals may also have abnormalities of the respiratory system. The lungs may be abnormally divided into small extra sections (lung lobulation) and/or the walls of the voice box (larynx) may be weak and easily collapsible, potentially resulting in swallowing and breathing difficulties (e.g., temporary cessation of normal breathing rhythm during sleep [sleep apnea]).
Individuals with RSTS can be difficult to intubate because of the easy collapsibility of the laryngeal wall. An anesthesiologist comfortable with managing complex pediatric airway problems should administer general anesthesia when needed.
Behavior
Individuals with RSTS often exhibit a short attention span, decreased tolerance for noise and crowds, impulsivity, aggressive behavior, repetitive behaviors and moodiness. Autistic behaviors are common.
Susceptibility to Malignancy
There are reports of persons with RSTS with various benign and malignant tumors including meningioma, pilomatixoma, rhabdomysarcoma, pheochromocytoma, neuroblastoma, medulloblastona, oligodendroglioma, leioyosarcoma, seminoma, odontoma, choristoma and leukemia. However, one recent study found only an increased risk for meningiomas and pilomatrixomas, but not for malignancies in general.
In most affected children, RSTS occurs as the result of a new (de novo) genetic mutation that is not present in or carried by the parents. In these cases, the risk of having a second affected child is less than 1%.
RSTS may also be inherited in an autosomal dominant pattern, meaning that if a person has RSTS, each of his/her children has a 50% chance of having RSTS.
The most common gene responsible for RSTS is the CREBBP gene. Pathogenic variants in the CREBBP gene have been identified in 50-60% of individuals with RSTS. Mutations in the EP300 gene have been identified in 8-10% of individuals with RSTS.
RSTS is a rare disorder that affects males and females in equal numbers. The exact incidence of RSTS is unknown, although a study in the Netherlands estimates the incidence to be between 1/100,000 to 1/125,000 individuals.
The diagnosis of RSTS is primarily based on physical (clinical) features, including short stature, a downward slant to the eyes (down slanted palpebral fissures), a low-hanging nasal septum (columella), a high palate, cusp-like structures (talon cusps) on the front teeth and/or broad and angulated thumbs and great toes. The diagnosis may be further supported by x-ray studies revealing malformations of the bones of the hands and feet characteristic to RSTS.
Genetic testing by sequencing of the CREBBP and EP300 genes or the use of large gene panels may confirm RSTS. Pathogenic variants may be detected in the CREBBP gene (identified in 50%-60% of affected individuals) or in the EP300 gene (identified in 8-10% of RSTS individuals).
Treatment
The management of RSTS is directed toward the specific symptoms of each individual. Management may require the coordinated efforts of a team of specialists, including pediatricians, physicians who diagnose and treat heart abnormalities (cardiologists), skeletal abnormalities (orthopedists), hearing problems (audiologists), urinary tract abnormalities (urologists), kidney dysfunction(nephrologists), as well as dental specialists, physical therapists, speech pathologists, dietitians and/or other health care professionals. Growth parameters should be regularly plotted on an RSTS-specific growth chart. There should be yearly eye and hearing evaluations and routine monitoring for cardiac, dental, and renal abnormalities.
Orthopedic surgery, physical therapy, and/or other supportive techniques may help treat certain skeletal differences associated with RSTS, such as scoliosis. In some cases, surgery may be performed on the hands and/or feet, particularly when the thumbs are angulated or the broad first toes make it difficult to wear shoes.
Affected individuals may require early intervention to prevent and/or monitor respiratory and feeding difficulties. Special education programs, vocational training, speech, and/or behavioral therapy may also be recommended.
Genetic counseling is recommended for affected individuals and their family members.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
INTERNET
Stevens CA. Rubinstein-Taybi Syndrome. 2002 Aug 30 [Updated 2019 Aug 22]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1526/ Accessed June 13, 2023.
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 180849, Last Update: 05/14/2019. Available at https://omim.org/entry/180849 Accessed June 13, 2023.
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Aprende más https://rarediseases.org/patient-assistance-programs/caregiver-respite/The information provided on this page is for informational purposes only. The National Organization for Rare Disorders (NORD) does not endorse the information presented. The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.
The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
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