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

bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...

s in the arms and

hand A hand is a prehensile, multi-fingered appendage located at the end of the forearm or forelimb of primates such as humans, chimpanzees, monkeys, and lemurs. A few other vertebrates such as the Koala#Characteristics, koala (which has two thumb#O ...

s (the upper limbs) and often causes

heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...

problems. The syndrome may include an absent radial bone in the forearm, an atrial septal defect in the heart, or heart block. It affects approximately 1 in 100,000 people.

Presentation

All people with Holt-Oram syndrome have at least one abnormal wrist bone, which can often only be detected by

X-ray An X-ray (also known in many languages as Röntgen radiation) is a form of high-energy electromagnetic radiation with a wavelength shorter than those of ultraviolet rays and longer than those of gamma rays. Roughly, X-rays have a wavelength ran ...

. 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 The clavicle, collarbone, or keybone is a slender, S-shaped long bone approximately long that serves as a strut between the shoulder blade and the sternum (breastbone). There are two clavicles, one on each side of the body. The clavicle is the ...

shoulder blade The scapula (: scapulae or scapulas), also known as the shoulder blade, is the bone that connects the humerus (upper arm bone) with the clavicle (collar bone). Like their connected bones, the scapulae are paired, with each scapula on either side ...

. 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. About 75 percent of individuals with Holt–Oram syndrome also have congenital heart problems, 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). People with Holt–Oram syndrome may also have abnormalities in the electrical system that coordinates contractions of the heart chambers. Cardiac conduction disease can lead to slow heart rate (

bradycardia Bradycardia, also called bradyarrhythmia, is a resting heart rate under 60 beats per minute (BPM). While bradycardia can result from various pathological processes, it is commonly a physiological response to cardiovascular conditioning or due ...

); rapid, ineffective contraction of the heart muscles ( fibrillation); and heart block. People with Holt-Oram syndrome may have only congenital heart defects, only cardiac conduction disease, both or neither.

Genetics

Mutations in the '' TBX5'' gene cause Holt–Oram syndrome. The ''TBX5'' gene produces a protein that is critical for the proper development of the heart and upper limbs before birth. Holt–Oram syndrome has an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

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. However, in 85 percent of cases, the gene mutation isn't inherited, but a new

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

Diagnosis

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. If the symptoms aren't enough to diagnose, a person may undergo

genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

for the mutations associated with the syndrome.

Treatment

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. Heart defects may call for surgery, medication, pacemakers or close monitoring. Pregnant women with Holt-Oram syndrome and heart abnormalities should be followed by a cardiologist during pregnancy.

History

It is named for Mary Holt and Samuel Oram, who published a paper on it in 1960.

References

External links

{{DEFAULTSORT:Holt-Oram syndrome Syndromes affecting the heart Autosomal dominant disorders Transcription factor deficiencies Congenital disorders Syndromes with dysmelia Rare syndromes