Brachydactyly

Definition

Brachydactyly (BD) refers to shortening of the fingers or toes due to underdevelopment of the bones in the hands or feet.

Description

The word brachydactyly comes from the Greek terms brachy, meaning "short," and daktylos, meaning "digit." This term is used to describe the hands and feet of people who have shortened digits (fingers or toes). The digits themselves may be shorter than normal, or they may appear small because of shortening of the other bones in the hands or feet. This shortening occurs when one or more of the hand or foot bones fail to develop or grow normally.

BD is usually isolated, meaning that it is not associated with any other medical problems. BD may occur along with other physical differences or health problems, often as part of a "syndrome."

BD occurs in a variety of patterns, depending upon which hand or foot bones are affected and how severely they are shortened. It is important to know some basic information about the bone structure of the hands and feet in order to understand the various patterns of BD. Beyond the wrist and ankle, each hand and foot contains 19 tube-shaped (tubular) bones in a specific arrangement. For purposes of orientation, the fingers and toes are numbered from one (thumb or great toe) to five (little finger or little toe). When a fist is made, the bones in the hand that extend from the wrist to the knuckles are called metacarpals. There are five metacarpals, one for the thumb (first metacarpal) and each finger. Each thumb and finger contains several bones called phalanges. A single one of these bones is called a phalanx. The phalanges are arranged end to end and are separated by joints. The thumb has two phalanges and each finger has three phalanges. The phalanges within a particular finger are named according to their location. The phalanges closest to the metacarpals are called the "proximal" phalanges, those in the middle of the fingers are called the "middle" phalanges, and those at the ends of the fingers are called the "distal" or "terminal" phalanges. The thumbs have only proximal and distal phalanges.

The foot bones are very similar to the hand bones. Like the metacarpals, there are five metatarsal bones that extend from the ankle to each of the toes. The bones in the toes are also called phalanges. There are two phalanges in the great toe and three phalanges in each of the other toes.

BD can involve any of the phalanges, metacarpals, and metatarsals in many different combinations. The shortening of these bones may range from mild to severe. Sometimes certain bones are completely absent. Shortening of the bones may occur in one, several, or all of the digits. For a particular finger or toe, the entire digit may be short or only a particular phalanx may be underdeveloped. When BD involves the distal phalanges, the fingernails or toenails may be small or absent. A digit may also be of normal length but appear short due to shortening of its corresponding metacarpal or metatarsal bone. Reduced length of a metacarpal bone is often easiest to appreciate when the hand is held in a fist.

BD can also occur with other abnormalities of the hands and feet. When a phalanx is abnormally shaped, the finger or toe may be bent to one side (clinodactyly). Sometimes the digits have webbing between them (syndactyly). The phalanges may also be fused together at their ends (symphalangism). This makes it difficult to bend a digit at the joint where the phalanges are fused.

BD frequently occurs in characteristic patterns that can be inherited through families. These patterns are classified as particular types of BD, depending upon which bones and which digits of the hands and/or feet are shortened. There are several classification systems used to describe these different types of BD. The system that is used most frequently was developed by Dr. Julia Bell in 1951 and is called the "Bell Classification."

There are five main types of BD in the Bell Classification, which are designated types A through E. Their major features are as follows:

• In type A, the middle phalanges of one, several, or all of the fingers and/or toes are shortened. This form of BD is further divided into types A1, A2, and A3. In type A1, the middle phalanges of all digits and the proximal phalanges of the thumbs and great toes are shortened. People with this form of BD generally have hands and feet that appear small with relatively equal shortening of all digits. In type A2, the middle phalanges of the index finger and second toe are shortened and often abnormally shaped. In type A3, the middle phalanx of the fifth finger is shortened and this finger often bends toward the fourth finger. Several other forms of BD type A have also been described.
• In type B, the distal phalanges and nails of the fingers and/or toes are small or absent. The middle phalanges may also be shortened, and the tips of the thumbs and/or great toes may be broad or have a "duplicated" (double) appearance. In this type of BD, the digits typically look as though their tips have been amputated.
• In type C, the middle phalanges of all of the fingers may be shortened, but the fourth finger is least affected and is often the longest finger. The index and middle fingers may be bent toward the fourth finger. The first metacarpal bone can also be short, making the thumb appear small.
• In type D, the distal phalanges of the thumbs and/or great toes are shortened and broad.
• In type E, the metacarpals and/or metatarsals are shortened. The fourth and fifth metacarpals and metatarsals are most commonly shortened, but any of them may be affected.

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).

Diagnosis

The diagnosis of BD is made when a person has shortening of the digits due to lack of normal growth and development of one or more bones in the hands or feet. When the bones are significantly shortened, this is easily noticed in the appearance of the hands and feet. When the shortening is mild, it may only be apparent on x rays. Some people may not realize that they have BD until told by a physician who has carefully examined their hands and feet.

X rays of the hands and feet are used to look at the bones in detail. A special analysis of the hand x rays called a "metacarpophalangeal profile" is often performed for people with BD. This involves measuring the length of each hand and finger bone. These measurements are then compared to the normal range of sizes for each bone. The metacarpophalangeal profile is used to identify particular patterns of BD. X rays may also reveal other bone changes that help to pinpoint a specific type of BD or another genetic condition. If a person has short stature or other bone changes, a series of x rays of the entire skeleton (skeletal survey) may be recommended.

Since BD is often inherited, detailed information about a person's relatives can be very important in evaluating someone with BD. A geneticist may wish to examine other family members or obtain x rays of their hands and feet. Because BD can occur in a variety of genetic conditions, a geneticist evaluating someone with BD will usually review his or her medical history and perform a detailed physical examination. The presence of other physical differences or medical problems may indicate that the brachydactyly is part of another condition rather than an isolated finding.

Laboratory tests are usually not helpful in diagnosing BD when it is an isolated finding. Although the genes for BD types B and C are known, testing of these genes is not routinely available or usually necessary. If a person with BD has signs or symptoms of another underlying condition, certain laboratory tests may be recommended. These tests may identify other associated medical problems or help to pinpoint a specific diagnosis.

Treatment and management

Many people who have BD are perfectly healthy and do not require any specific treatment for their hands and feet. When use of the hands is impaired, physical therapy or hand exercises may improve grip strength or flexibility. Evaluation by an orthopedist or physical therapist may also be helpful for people who have trouble walking comfortably due to bone changes in the feet. Surgery can be used to lengthen the hand or foot bones in some severe forms of BD. Surgery may also be helpful for people who have significant clinodactyly, syndactyly, or symphalangism. For most people with BD, however, surgery is not needed. If BD is associated with other medical problems, such as hypertension, specific treatments for these problems may be indicated.

Prognosis

Isolated BD generally has an excellent prognosis. When BD is associated with other health problems or is part of another condition, the overall prognosis depends upon the nature of the associated condition.

Resources

BOOKS

Temtamy, Samia A., and Victor A. McKusick. The Genetics of Hand Malformations. New York: Alan R. Liss, 1978.

Winter, Robin M., Richard J. Schroer, and Leslie C. Meyer. "Hands and Feet." In Human Malformations. Vol. 2, edited by Roger E. Stevenson, Judith G. Hall, and Richard M. Goodman, New York: Oxford University Press, 1993, pp. 828–43.

PERIODICALS

Armour, C. M., D. E. Bulman, and A. G. W. Hunter. "Clinical and Radiological Assessment of a Family with Mild Brachydactyly Type A1: The Usefulness of Metacarpophalangeal Profiles." Journal of Medical Genetics 37 (April 2000): 292–296.

Oldridge, M., et al. "Dominant Mutations in ROR2, Encoding an Orphan Receptor Tyrosine Kinase, Cause Brachydactyly Type B." Nature Genetics 24 (March 2000): 275–78.

Polinkovsky, A., et al. "Mutations in CDMP1 Cause Autosomal Dominant Brachydactyly Type C." Nature Genetics 17 (September 1997): 18–19.

WEBSITES

Online Mendelian Inheritance in Man (OMIM). <http://www.ncbi.nlm.nih.gov/Omim/>.

David B. Everman, MD