Question: What are the symptoms of Holt-Oram syndrome ?
Answer: What are the signs and symptoms of Holt-Oram syndrome? 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. Additional bone abnormalities may also be present, such as 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. About 75% of affected people have heart problems, which can be life-threatening. The most common problems are an atrial septal defect (ASD) and a ventricular septal defect (VSD). Some people 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). The features of Holt-Oram syndrome are similar to those of a condition called Duane-radial ray syndrome but these two disorders are caused by mutations in different genes. The Human Phenotype Ontology provides the following list of signs and symptoms for Holt-Oram syndrome. If the information is available, the table below includes how often the symptom is seen in people with this condition. You can use the MedlinePlus Medical Dictionary to look up the definitions for these medical terms. Signs and Symptoms Approximate number of patients (when available) Abnormality of the wrist 90% Abnormality of the metacarpal bones 50% Aplasia/Hypoplasia of the radius 50% Aplasia/Hypoplasia of the thumb 50% Arrhythmia 50% Atria septal defect 50% Triphalangeal thumb 50% Ventricular septal defect 50% Hypoplasia of the radius 37.8% Phocomelia 11% Abnormality of the aorta 7.5% Abnormality of the humerus 7.5% Abnormality of the ribs 7.5% Abnormality of the shoulder 7.5% Abnormality of the sternum 7.5% Anomalous pulmonary venous return 7.5% Aplasia of the pectoralis major muscle 7.5% Complete atrioventricular canal defect 7.5% Finger syndactyly 7.5% Hypoplastic left heart 7.5% Patent ductus arteriosus 7.5% Pectus excavatum 7.5% Radioulnar synostosis 7.5% Scoliosis 7.5% Sprengel anomaly 7.5% Thoracic scoliosis 7.5% Abnormality of the carpal bones - Abnormality of the vertebrae - Absent thumb - Autosomal dominant inheritance - Partial duplication of thumb phalanx - The Human Phenotype Ontology (HPO) has collected information on how often a sign or symptom occurs in a condition. Much of this information comes from Orphanet, a European rare disease database. The frequency of a sign or symptom is usually listed as a rough estimate of the percentage of patients who have that feature. The frequency may also be listed as a fraction. The first number of the fraction is how many people had the symptom, and the second number is the total number of people who were examined in one study. For example, a frequency of 25/25 means that in a study of 25 people all patients were found to have that symptom. Because these frequencies are based on a specific study, the fractions may be different if another group of patients are examined. Sometimes, no information on frequency is available. In these cases, the sign or symptom may be rare or common.
Source: GARD

Question: Is Holt-Oram syndrome inherited ?
Answer: How is Holt-Oram syndrome inherited? Holt-Oram syndrome (HOS) is inherited in an autosomal dominant manner. This means that having only one changed (mutated) copy of the responsible gene in each cell is enough to cause signs and symptoms of the condition. In most cases, the mutation in the gene occurs for the first time in the affected person and is not inherited from a parent. When a mutation occurs for the first time, it is called a de novo mutation. This is what typically occurs when there is no family history of the condition. A de novo mutation is due to a random change in the DNA in an egg or sperm cell, or right after conception. In some cases, an affected person inherits the mutated copy of the gene from an affected parent. In these cases, the symptoms and severity can differ from those of the affected parent. When a person with an autosomal dominant condition has children, each child has a 50% (1 in 2) risk to inherit the condition.
Source: GARD

Question: How to diagnose Holt-Oram syndrome ?
Answer: How is Holt-Oram syndrome diagnosed? The diagnosis of Holt-Oram syndrome can be established based on physical features and family history. It can be confirmed through genetic testing looking for mutations in the TBX5 gene. Hand x-rays are usually performed for upper-limb malformations. A family history of this condition and/or cogenital heart malformations is also used as a diagnostic tool as a congenital heart malformation is present in 75% of individuals with Holt-Oram syndrome. An echocardiogram and electrocardiogram can be used to determine the presence and severity of heart defects and/or cardiac conduction disease. Holt-Oram syndrome can be excluded in individuals with congenital malformations involving the following structures or organ systems: ulnar ray only, kidney, vertebra, head and face region, auditory system (hearing loss or ear malformations), lower limb, anus, or eye.
Source: GARD

Question: What are the treatments for Holt-Oram syndrome ?
Answer: How might Holt-Oram syndrome be treated? The treatment of Holt-Oram syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists such as pediatricians, surgeons, cardiologists, orthopedists, and/or other health care professionals. Depending upon the severity of any upper limb abnormalities, treatment may consist of corrective or reconstructive surgery, the use of artificial replacements for portions of the forearms and hands (limb prosthetics), and/or physical therapy to help individuals enhance their motor skills. In those with mild cardiac conduction abnormalities, treatment may not be required. In more severe cases, an artificial pacemaker may be used. An artificial pacemaker overrides the heart's impaired electrical conducting system by sending electrical impulses to the heart that keep the heartbeat at a regular rate. Heart abnormalities may also be treated with certain medications, surgery, and/or other techniques. In such cases, the surgical procedures performed will depend upon the location and severity of the abnormalities and their associated symptoms. Affected individuals with heart defects may also be at risk for bacterial infection and inflammation of the lining of the heart's chambers and valves (endocarditis). So antibiotics should be prescribed before any surgical procedure, including dental procedures such as tooth extractions. In addition, because some individuals with certain heart defects may be susceptible to repeated respiratory infections, physicians may closely monitor such individuals to take preventive steps and to institute antibiotic and/or other appropriate therapies should such infections occur. Early intervention is important to ensure that children with Holt-Oram syndrome reach their potential. Special services that may be beneficial to affected children may include physical therapy and/or other medical, social, and/or vocational services.
Source: GARD