Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
Age of Onset
Autosomal dominant ?A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease
Autosomal recessive ?Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype
X-linked dominant ?X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.
X-linked recessive ?Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder
Mitochondrial or multigenic ?Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.
Multigenic or multifactor ?Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.
Other Names (AKA)
Heart-hand syndrome; HOS; Atriodigital dysplasia;
Congenital and Genetic Diseases; Heart Diseases; Musculoskeletal Diseases
Holt-Oram syndrome is caused by genetic changes (pathogenic variants or
About 75% of people who have Holt-Oram syndrome have heart problems. The most common problems are holes in the walls that separate the heart into four areas (chambers). These heart defects are known as atrial septal defects (ASD) or ventricular septal defects (VSD) depending on the exact location of the hole. Other heart defects including patent ductus arteriosus (PDA) have been reported. The heart defects associated with Holt-Oram syndrome may not cause any problems or may cause symptoms such as having a hard time breathing, tiring easily (fatigue), having
Some people with Holt-Oram syndrome have cardiac conduction disease, which is when the electrical system that coordinates the heartbeat does not work correctly. Cardiac conduction disease can lead to problems such as a slower than expected heart rate (bradycardia) or a rapid and uncoordinated contraction of the heart muscle (fibrillation). Health problems associated with cardiac conduction disease may be more likely to develop as a person gets older.
The symptoms of Holt-Oram syndrome are similar to those of another syndrome called Duane-radial ray syndrome. However, these syndromes are caused by genetic changes (pathogenic variants or
This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.
|Medical Terms||Other Names||
|80%-99% of people have these symptoms|
|Abnormal clavicle morphology||
[ more ]
Claw hand deformities
[ more ]
|30%-79% of people have these symptoms|
|Abnormality of the metacarpal bones||
Abnormality of the long bone of hand
|Aplasia/Hypoplasia of the radius||0006501|
|Atrial septal defect||
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers
[ more ]
|First degree atrioventricular block||0011705|
[ more ]
|Paroxysmal atrial fibrillation||0004757|
|Ventricular septal defect||
Hole in heart wall separating two lower heart chambers
|5%-29% of people have these symptoms|
|Abnormal aortic morphology||0001679|
|Abnormality of the humerus||0003063|
|Abnormality of the ribs||
|Anomalous pulmonary venous return||0010772|
|Atrioventricular canal defect||0006695|
[ more ]
Rounded, sloping shoulders
[ more ]
|Hypoplastic left heart||
Underdeveloped left heart
|Patent ductus arteriosus||0001643|
Fused forearm bones
High shoulder blade
|1%-4% of people have these symptoms|
Missing outer large bone of forearm
|Aplasia of the pectoralis major muscle||0009751|
|Aplasia of the ulna||0003982|
|Hypoplasia of the radius||
Underdeveloped outer large forearm bone
|Hypoplasia of the ulna||
Underdeveloped inner large forearm bone
|Limited elbow extension||
Decreased elbow extension
Elbow limited extension
Limitation of elbow extension
Limited extension at elbows
Limited forearm extension
Restricted elbow extension
[ more ]
|Secundum atrial septal defect||0001684|
Short long bone of upper arm
Short upper arms
[ more ]
|Small thenar eminence||0001245|
Webbed fingers or toes
|Percent of people who have these symptoms is not available through HPO|
|Abnormal vertebral morphology||0003468|
|Abnormality of the carpal bones||0001191|
Partial duplication of the thumb bones
In some cases, people with Holt-Oram syndrome are not found to have pathogenic variants in the TBX5 gene. In these cases, the exact cause of Holt-Oram syndrome is not understood.
- The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
- Orphanet lists international laboratories offering diagnostic testing for this condition.
People with mild heart defects or cardiac conduction disease may not require any treatment. In other cases, cardiac conduction disease may be treated with antiarrhythmic medications or a pacemaker to maintain a regular heart rate. Other heart abnormalities may be treated with surgery. The specific surgical procedure will depend on the location and severity of the heart defect.
People with heart defects may be at an increased risk for bacterial infection and inflammation of the lining of the heart’s chambers and valves (endocarditis).
Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.
Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes heart-hand syndrome type 2, heart-hand syndrome type 3, brachydactyly-long thumb, SAL4-related disorders (Okihiro and acro-renal-ocular syndrome), ulnar-mammary syndrome, Slovenian type heart-hand syndrome, Fanconi anemia, distal 22q11.2 microdeletion syndrome, VACTERL association, thalidomide embryopathy, fetal valproate syndrome.
Visit the Orphanet disease page for more information.
Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.
Kids with Heart National Association for Children's Heart Disorders
1578 Careful Drive
Green Bay, WI 54304
These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.
- Genetics Home Reference (GHR) contains information on Holt-Oram syndrome. This website is maintained by the National Library of Medicine.
- The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
- GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
- Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
- The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
- Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
- Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
- PubMed is a searchable database of medical literature and lists journal articles that discuss Holt-Oram syndrome. Click on the link to view a sample search on this topic.
- Holt-Oram Syndrome. Genetics Home Reference. June 2014; https://ghr.nlm.nih.gov/condition/holt-oram-syndrome.
- Picache J and Basson CT. Holt Oram Syndrome. National Organization for Rare Disorders (NORD). 2017; https://rarediseases.org/rare-diseases/holt-oram-syndrome/.
- Sinha R and Nema C. Rare cardiac defect in Holt-Oram syndrome. Cardiovascular Journal of Africa. March 12, 2012; 23(2):e3-4. https://www.ncbi.nlm.nih.gov/pubmed/22447508.
- McDermott DA, Fong JC, Basson CT. Holt-Oram Syndrome. GeneReviews. October 8, 2015; https://www.ncbi.nlm.nih.gov/books/NBK1111/.
- Basson CT, Vaughan CJ, Kim LK, and McDermott DA. Holt-Oram Syndrome. Medscape Reference. May 5, 2016; https://emedicine.medscape.com/article/159911-overview.