Brachydactyly Health Article

Genetic profile

Many different genetic signals are required for normal formation of the hand and foot bones. BD is usually caused by abnormalities in these genetic blueprints. Sometimes BD can be caused by exposure to drugs or medications taken during pregnancy. Problems with blood flow to the hands or feet during fetal life may also cause BD.

The types of BD in the Bell Classification are inherited in families from one generation to the next. Their pattern of inheritance is called autosomal dominant. This means that they are caused by abnormalities in only one copy of a gene from a particular gene pair. In fact, one form of BD (type A1) was the first human condition that was recognized to have this type of inheritance pattern. Autosomal dominant forms of BD can be inherited by a child of either sex from a parent of either sex. The gene change causing BD may also occur in a particular person for the very first time within a family. Each child born to a person having autosomal dominant BD has a 50% chance of also having BD. However, the degree of hand or foot abnormalities can be very different between people with the same type of BD, and even among members of the same family.

Until recently, nothing was known about the genes that cause BD. This has changed with the identification of the genes that cause two forms of autosomal dominant BD (types B and C) in the past several years. The gene causing BD type C was the first to be identified in 1997. The name of this gene is the "Cartilage Derived Morphogenetic Protein 1" gene, abbreviated as CDMP1. This gene is located on the long arm of chromosome 20 (at location 20q11.2) and provides an important genetic signal to the developing bones of the limbs. Most people with BD type C have abnormalities in one of their two copies of this gene.

The gene causing BD type B was identified in 2000. This gene is called ROR2 and is located on the long arm of chromosome 9. Like CDMP1, ROR2 also provides an important genetic blueprint for the normal development of bones. BD type B is caused by alterations in one copy of this gene.

One interesting feature of the CDMP1 and ROR2 genes is that they can also cause other medical conditions with bone problems that are much more severe than BD. This happens when both copies of either gene are altered in the same person. The genes for other types of autosomal dominant BD have not yet been discovered.

Demographics

BD occurs in people of many different racial and ethnic backgrounds. It is difficult to determine the overall frequency of BD in the general population because many people who have BD never seek medical attention for their shortened digits. Types A3 and D are the most common forms of BD, but their frequencies vary widely between groups of people from different backgrounds. For example, type A3 has been found in fewer than 1% of Americans, compared to 21% of Japanese people. Because isolated forms of BD are generally inherited as autosomal dominant traits, they should affect males and females in equal numbers. However, several types of BD may be more common in females.

Signs and symptoms

BD is often evident at birth, but may also develop or become more obvious during childhood. It usually does not cause pain or other physical symptoms. In fact, many people who have BD consider it to be a normal family trait rather than a medical condition. When BD does cause problems, they are usually related to the size, appearance, or function of the hands or feet. The altered appearance of the hands or feet may make persons with BD feel self-conscious. Shortening of the digits may also make it difficult to find comfortable shoes or gloves. In its severe forms, BD may affect a person's ability to grip objects or participate in certain jobs or leisure activities. Hand function may be especially affected when BD is associated with clinodactyly, syndactyly, or symphalangism. When BD is associated with significant deformities of the feet, walking may be difficult or painful.

In some cases, BD occurs in combination with other physical changes or medical problems. For instance, people with autosomal dominant forms of BD are often shorter than expected and may have other alterations of the skeleton besides short digits. Some people with BD type E also have hypertension (high blood pressure). BD may also be present as one finding in a number of different genetic conditions (syndromes).