Holt Oram Syndrome

Holt Oram Syndrome is a genetic disease that impacts physical development and also gives rise to cardiac problems. Find out all about this condition, including its causes, symptoms, diagnosis and treatment.

Holt Oram Syndrome Definition

It is an autosomal dominant genetic condition that leads to congenital heart defects (cardiac conduction problems) along with skeletal abnormalities in the hand and arm. In individuals affected with this disease, at least one abnormality in the development of the wrist bones (carpal bones) is common. This disorder is related with the TBX5 gene.

Picture of Holt Oram Syndrome

Picture 1 – Holt Oram Syndrome

Holt Oram Syndrome Synonyms

This condition is also known by other names, such as:


  • Atriodigital Dysplasia
  • Upper Limb–Cardiovascular Syndrome
  • Hand-Heart Syndrome
  • Cardiac-Limb Syndrome
  • Thumb Abnormality
  • Familial Heart Disease with Skeletal Malformations,
  • Heart-Hand Syndrome
  • Pseudothalidomide Syndrome
  • Cardiomelic Syndrome
  • HOS1

Holt Oram Syndrome Causes

An inherited disorder, HOS1 is generally believed to occur due to a mutation in the TBX5 gene. This gene plays a key role in controlling the growth of bones in the hand and the arm. TBX5 also plays a dominant role in the course that segments the heart into four chambers. A mutation in this gene disrupts the normal growth of the upper limbs and heart, thereby causing this disorder.

Holt Oram Syndrome Symptoms

Atriodigital Dysplasia arises with a few warning signs that serve as indicators of its occurrence in the body of a patient. The symptoms of this disorder can be majorly categorized into two parts:

Heart abnormalities

More than 75% of individuals affected with HOS1 syndrome suffer from heart disorders. In a few cases, patients suffer from cardiac defects like Ventricular Septal Defect (VSD) or Artrial Septal Defect (ASD). Such individuals may also experience abnormal heart rhythms which confirm the existence of this ailment.

Arm and hand defects

Abnormality in the bones of hand or arm is common among patients suffering from HOS1.  The defects are generally observed in the carpal bones of the wrist and the thumb bones. In a few cases, the entire thumb may be missing. A few patients with this disorder have short arms which are attached very close to the body. Such a condition is known as Phocomelia.

Other Symptoms

There are a variety of other warning signs which indicate the presence of HOS1. Such symptoms include:

  • Syndactyly
  • Underdeveloped radius
  • Ulna defects
  • Humerus defects
  • Reduced range of elbow motion
  • Underdeveloped thumbs
  • Triphalangeal thumbs
  • Split thumbs
  • Reduced range of shoulder motion
  • Narrow shoulders
  • Clavicle defects
  • Scapula defects
  • Sternum defects
  • Absence of first metacarpal
  • Absence of radius
  • Underdeveloped first metacarpal
  • Sloping shoulders
  • Underdeveloped scaphoid
  • Finger like thumb
  • Underdeveloped forearm
  • Ostium secundum atrial septal defect
  • Arrhythmia
  • Ventricular septal defect
  • Congenital heart defects
  • Underdeveloped arm blood vessels
  • Underdeveloped leg blood vessels
  • Carpal bone (wrist) abnormality
  • Missing thumb
  • Partial absence of forearm bones
  • Complete absence of forearm bones
  • Underdeveloped upper arm bone
  • Collar bone abnormalities
  • Shoulder blade abnormality
  • Heart septum defect
  • Atrial septal defects
  • Ventricle septal defects
  • Heart conduction disease
  • Slow heart rate
  • Heart fibrillation

Holt Oram Syndrome Diagnosis

A congenial disorder, HOS1 can be diagnosed on the basis of arm and hand abnormality. If the defect is not so severe, diagnosis is not recommended. Tests are done when cardiac symptoms begin to manifest at a later stage in the life of a patient. The bone and cardiac abnormalities in HOS1 patients can be detected by the use of:

  • Echocardiogram
  • X-ray
  • Electrocardiogram

Holt Oram Syndrome Treatment

The treatment for this condition is mainly focused on curing its symptoms. Patients suffering from this disease can suffer from sudden heart failure due to severe heart defects. Hence, they are highly recommended to consult a cardiologist. Children, who suffer from arm defects due to the syndrome, should consult orthopedic surgeons to enhance their hand movements. In a few cases, a permanent pacemaker is implanted in patients with severe heart blockage. Surgical therapy is often recommended to HOS1-affected patients to enhance their limb movement and treat cardiac defects.

The anatomical defects arising due to this syndrome cannot be cured by any medicine. Patients suffering from congenital heart disease can be administered by antibiotic prophylaxis. Patients with Atrial Fibrillation can avail of antiarrhythmic drug therapy, cardioversion or anticoagulation.

Holt Oram Syndrome Prognosis

HOS is inherited in an autosomal dominant pattern. This signifies that, any of the parents may carry the affected gene (TBX5) which can be inherited by the new born child. Hence, it is mandatory that once an individual has been screened with this syndrome, his/her family members are diagnosed properly to determine the existence of HOS1.

Holt Oram Syndrome Complications

The various complications arising in HOS patients, either due to lack of treatment or care, may include:

Image of Holt Oram Syndrome

Picture 2 – Holt Oram Syndrome Image

  • Atrial fibrillation
  • Infectious endocarditis
  • Arrhythmia
  • Sudden death
  • Congestive heart failure

As aforementioned, Holt Oram Syndrome is a complicated skeletal disorder that can lead to severe heart defects and even cause death. Naturally, it is important to seek appropriate treatment and care on an immediate basis once you spot its early signs. If you or any of your family members experience the symptoms of this disorder, consult a professional health care provider immediately. Timely cure and management would help you avert all possible complications and check this disease in its early stages, thus ensuring a better and faster recovery.

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