Texas Medical Center NEWS


Vol. 22, No. 15		August 15, 2000

Scientists Search for Clubfoot Genes

by RONDA WENDLER
Shriners Hospitals for Children-Houston

(Part 3 of 3)

"These statistics strongly suggest an underlying genetic factor in clubfoot." - Dr. Jacqueline Hecht

For years, studies have suggested that genetics may play a role in causing congenital clubfoot. Now, scientists at Shriners Hospital for Children in Houston are conducting a study to locate the gene or genes that cause this condition. Shriners scientific staff member, Jacqueline Hecht, Ph.D., who is also a professor at The University of Texas-Houston Medical School, has received a grant from Shriners Hospital's National Headquarters in Tampa, Fla., to fund the search for clubfoot genes.

Clubfoot is a common birth defect that occurs in one out of every 1,000 births. When other family members are affected, there is a higher birth prevalence suggesting that there are hereditary factors contributing to the development of clubfoot. If a family has one child with a clubfoot, the risk in subsequent siblings is about 20 times higher than average. Moreover, male relatives of a female patient appear to be at higher risk, and identical twins are more often affected than other siblings.

"These statistics strongly suggest an underlying genetic factor in clubfoot," Dr. Hecht says, "and we suspect that more than one gene is involved."

Dr. Hecht is collecting blood and cheek cell samples from individuals with clubfoot, their parents and siblings in order to identify the genes contributing to this foot deformity. To date, more than 800 samples have been collected from more than 300 families.

Juanita Cortes and her son Mario are among those participating in the study.

Mario, age 10, was born with clubfoot, and underwent therapy and surgery at Shriners Hospital as an infant to correct the deformity. Today, doctors describe his clubfoot as "completely corrected."

"I've always questioned why Mario was born with clubfoot. Perhaps the genetics study will provide an answer," Juanita says.

The genes that are being targeted for the clubfoot study are those known to be involved in the development of arms, legs, hands and feet.

"We're using a `candidate' gene approach ... we believe the genes that are involved in normal limb development may change (mutate) and cause clubfoot," Dr. Hecht explains.

Genes from individuals with and without clubfoot will be compared, and the genetic differences that are found may help to identify the genes contributing to clubfoot. Locating the genes for clubfoot will eventually allow researchers to identify individuals who are at risk to have children with the condition. This knowledge will help parents and health care professionals to strategize and prepare the best course of action for families-at-risk, and to develop better treatments, Dr. Hecht concludes.

Why Clubfoot Occurs

The majority of clubfoot cases result from abnormal development of the muscles, tendons, and bones while the fetus is forming in the uterus. The disturbance in normal growth of the foot probably occurs at about the eighth week of pregnancy.

In pinpointing the specific causes of clubfoot, researchers classify the condition, based on reasons for occurrence, into four major groups: congenital, teratologic, syndrome complex, or positional.

Congenital clubfoot is by far the most common form of clubfoot and is also referred to as "idiopathic" clubfoot, meaning that the condition arises spontaneously from an unknown cause. A child with congenital clubfoot has no other abnormalities, and the clubfoot is an isolated incident. The condition occurs more frequently within certain families, prompting scientists to believe that genetics play an important role in causing congenital clubfoot.
Teratologic clubfoot occurs as a part of an underlying neuromuscular disorder, such as spina bifida or arthrogryposis multiplex congenita. Clubfoot may or may not be present in children with these disorders. Teratologic clubfoot often is severe and nearly always requires early, radical surgery to achieve correction.
Syndrome Complex clubfoot occurs when a child is born with one of a number of genetic disorders, and clubfoot is part of the bigger disorder. Children with chromosomal abnormalities such as Down syndrome may also have Syndrome Complex clubfoot.
Positional clubfoot occurs when an otherwise normal foot is held in a deformed position in utero, and thus is "molded" incorrectly. A small uterus, the presence of twins and abnormal fetal position have all been associated with positional clubfoot, although many such pregnancies result in babies without clubfoot. Positional clubfoot responds readily to non-surgical treatments, such as splinting and casting. Because positional clubfoot is not an inherent defect, but instead a "packaging" problem, some physicians do not consider it a true clubfoot.

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