Holt-Oram syndrome | |
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Other names | Heart-hand syndrome, Atrio-digital syndrome, Atriodigital dysplasia |
Holt-Oram syndrome has an autosomal dominant pattern of inheritance | |
Specialty | Medical genetics |
Causes | Mutations in the TBX5 gene |
Holt–Oram syndrome (also called atrio-digital syndrome, atriodigital dysplasia, cardiac-limb syndrome, heart-hand syndrome type 1, HOS, ventriculo-radial syndrome) is an autosomal dominant disorder that affects bones in the arms and hands (the upper limbs) and often causes heart problems. [1] The syndrome may include an absent radial bone in the forearm, an atrial septal defect in the heart, or heart block. [2] It affects approximately 1 in 100,000 people. [2]
All people with Holt-Oram syndrome have, at least one, abnormal wrist bone, which can often only be detected by X-ray. [1] Other bone abnormalities are associated with the syndrome. These vary widely in severity, and include a missing thumb, a thumb that looks like a finger, upper arm bones of unequal length or underdeveloped, partial or complete absence of bones in the forearm, and abnormalities in the collar bone or shoulder blade. [1] [2] Bone abnormalities may affect only one side of the body or both sides; if both sides are affected differently, the left side is usually affected more severely. [1]
About 75 percent of individuals with Holt–Oram syndrome also have congenital heart problems, [2] with the most common being defects in the tissue wall between the upper chambers of the heart ( atrial septal defect) or the lower chambers of the heart ( ventricular septal defect). [3] People with Holt–Oram syndrome may also have abnormalities in the electrical system that coordinates contractions of the heart chambers. [1] Cardiac conduction disease can lead to slow heart rate ( bradycardia); rapid, ineffective contraction of the heart muscles ( fibrillation); and heart block. [1] [2] People with Holt-Oram syndrome may have only congenital heart defects, only cardiac conduction disease, both or neither. [1] [2]
Mutations in the TBX5 gene cause Holt–Oram syndrome. [1] The TBX5 gene produces a protein that is critical for the proper development of the heart and upper limbs before birth. [1]
Holt–Oram syndrome has an autosomal dominant pattern of inheritance, meaning one abnormal copy of the gene is sufficient to cause disease, which each child has a 50% chance of inheriting from an affected parent. [1] However, in 85 percent of cases, the gene mutation isn't inherited, but a new mutation. [2]
Diagnosis may be made on physical features alone, if a person has an arm or hand bone abnormality and a personal or family history of heart problems. [2] If the symptoms aren't enough to diagnose, a person may undergo genetic testing for the mutations associated with the syndrome. [2]
A person with Holt-Oram syndrome may need various treatments, depending on how the syndrome manifests. Surgery, prosthetics and physical or occupational therapy can help people with bone abnormalities. [2] Heart defects may call for surgery, medication, pacemakers or close monitoring. [2] Pregnant women with Holt-Oram syndrome and heart abnormalities should be followed by a cardiologist during pregnancy. [2]
It is named for Mary Holt and Samuel Oram, who published a paper on it in 1960. [4] [5]