What is Holt-Oram syndrome?
Holt-Oram syndrome is characterized by skeletal
abnormalities of the hands and arms (upper limbs) and heart problems.
People with Holt-Oram syndrome have abnormally developed
bones in their upper limbs. At least one abnormality in the bones of the wrist
(carpal bones) is present in affected individuals. Often, these wrist bone
abnormalities can be detected only by X-ray. Individuals with Holt-Oram
syndrome may have additional bone abnormalities including a missing thumb, a
long thumb that looks like a finger, partial or complete absence of bones in
the forearm, an underdeveloped bone of the upper arm, and abnormalities of the
collar bone or shoulder blades. These skeletal abnormalities may affect one or
both of the upper limbs. If both upper limbs are affected, the bone
abnormalities can be the same or different on each side. In cases where the
skeletal abnormalities are not the same on both sides of the body, the left
side is usually more severely affected than the right side.
About 75 percent of individuals with Holt-Oram syndrome have
heart (cardiac) problems, which can be life-threatening. The most common
problem is a defect in the muscular wall (septum) that separates the right and
left sides of the heart. A hole in the septum between the upper chambers of the
heart (atria) is called an atrial septal defect (ASD), and a hole in the septum
between the lower chambers of the heart (ventricles) is called a ventricular
septal defect (VSD). Some people with Holt-Oram syndrome have cardiac
conduction disease, which is caused by abnormalities in the electrical system
that coordinates contractions of the heart chambers. Cardiac conduction disease
can lead to problems such as a slower-than-normal heart rate (bradycardia) or a
rapid and uncoordinated contraction of the heart muscle (fibrillation). Cardiac
conduction disease can occur along with other heart defects (such as ASD or
VSD) or as the only heart problem in people with Holt-Oram syndrome.
The features of Holt-Oram syndrome are similar to those of a
condition called Duane-radial ray syndrome; however, these two disorders are
caused by mutations in different genes.
Holt-Oram syndrome is estimated to affect 1 in 100,000
individuals.
Mutations in the TBX5 gene cause Holt-Oram syndrome.
This gene provides instructions for making a protein that plays a role in the
development of the heart and upper limbs before birth. In particular, this gene
appears to be important for the process that divides the developing heart into
four chambers (cardiac septation). The TBX5 gene also appears to play a
critical role in regulating the development of bones in the arm and hand.
Mutations in this gene probably disrupt the development of the heart and upper
limbs, leading to the characteristic features of Holt-Oram syndrome.
This condition is inherited in an autosomal dominant
pattern, which means one copy of the altered gene in each cell is sufficient to
cause the disorder.
Most cases result from new mutations in the gene and occur
in people with no history of the disorder in their family.
·
Atriodigital dysplasia
·
Atrio-digital syndrome
·
Cardiac-limb syndrome
·
Heart-hand syndrome, type 1
·
HOS
·
Ventriculo-radial syndrome
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