Dupuytren contracture is characterized by a deformity of the hand in which the joints of one or more fingers cannot be fully straightened (extended); their mobility is limited to a range of bent (flexed) positions. The condition is a disorder of connective tissue, which supports the body's muscles, joints, organs, and skin and provides strength and flexibility to structures throughout the body. In particular, Dupuytren contracture results from shortening and thickening of connective tissues in the hand, including fat and bands of fibrous tissue called fascia; the skin is also involved.

In men, Dupuytren contracture most often occurs after age 50. In women, it tends to appear later and be less severe. However, Dupuytren contracture can occur at any time of life, including childhood. The disorder can make it more difficult or impossible for affected individuals to perform manual tasks such as preparing food, writing, or playing musical instruments.

Dupuytren contracture often first occurs in only one hand, affecting the right hand twice as often as the left. About 80 percent of affected individuals eventually develop features of the condition in both hands.

Dupuytren contracture typically first appears as one or more small hard nodules that can be seen and felt under the skin of the palm. In some affected individuals the nodules remain the only sign of the disorder, and occasionally even go away without treatment, but in most cases the condition gradually gets worse. Over months or years, tight bands of tissue called cords develop. These cords gradually draw the affected fingers downward so that they curl toward the palm. As the condition worsens, it becomes difficult or impossible to extend the affected fingers. The fourth (ring) finger is most often involved, followed by the fifth (little), third (middle), and second (index) fingers. Occasionally the thumb is involved. The condition is also known as Dupuytren disease, and "Dupuytren contracture" most accurately refers to later stages when finger mobility is affected; however, the term is also commonly used as a general name for the condition.

About one-quarter of people with Dupuytren contracture experience uncomfortable inflammation or sensations of tenderness, burning, or itching in the affected hand. They may also feel pressure or tension, especially when attempting to straighten affected joints.

People with Dupuytren contracture are at increased risk of developing other disorders in which similar connective tissue abnormalities affect other parts of the body. These include Garrod pads, which are nodules that develop on the knuckles; Ledderhose disease, also called plantar fibromatosis, which affects the feet; scar tissue in the shoulder that causes pain and stiffness (adhesive capsulitis or frozen shoulder); and, in males, Peyronie disease, which causes abnormal curvature of the penis.

While the cause of Dupuytren contracture is unknown, changes in one or more genes are thought to affect the risk of developing this disorder. Some of the genes associated with the disorder are involved in a biological process called the Wnt signaling pathway. This pathway promotes the growth and division (proliferation) of cells and is involved in determining the specialized functions a cell will have (differentiation).

Abnormal proliferation and differentiation of connective tissue cells called fibroblasts are important in the development of Dupuytren contracture. The fascia of people with this disorder has an excess of myofibroblasts, which are a type of fibroblast containing protein strands called myofibrils. Myofibrils normally form the basic unit of muscle fibers, allowing them to contract. The increased number of myofibroblasts in this disorder cause abnormal contraction of the fascia and produce excess amounts of a connective tissue protein called type III collagen. The combination of abnormal contraction and excess type III collagen likely results in the changes in connective tissue that occurs in Dupuytren contracture. However, it is unknown how changes in genes that affect the Wnt signaling pathway are related to these abnormalities and how they contribute to the risk of developing this disorder.

Other risk factors for developing Dupuytren contracture may include smoking; extreme alcohol use; liver disease; diabetes; high cholesterol; thyroid problems; certain medications, such as those used to treat epilepsy (anticonvulsants); and previous injury to the hand.

Normal Function

The SFRP4 gene provides instructions for making a protein called secreted frizzled-related protein 4 (SFRP4). This protein blocks (inhibits) a process called Wnt signaling. Wnt signaling plays an important role in the development of several tissues and organs throughout the body. In particular, regulation of this signaling process by SFRP4 is critical for normal bone development and remodeling. Bone remodeling is a normal process in which old bone is broken down and new bone is created to replace it. The SFRP4 protein also plays a role in the development of fatty (adipose) tissue.

Health Conditions Related to Genetic Changes

Pyle disease

At least four SFRP4 gene mutations have been found in individuals with a bone disorder called Pyle disease. This condition is characterized by a bone abnormality in which the ends (metaphyses) of the long bones in the arms and legs are abnormally wide, resembling a boat oar or paddle. Other bones may also be abnormal in Pyle disease, including the collar bones (clavicles), ribs, and bones in the fingers and hands. The SFRP4 gene mutations are thought to lead to production of an abnormally short SFRP4 protein with impaired function, or they result in no SFRP4 protein production at all. Studies suggest that loss of functional SFRP4 dysregulates Wnt signaling, which disrupts normal bone development and remodeling. Abnormal bone formation leads to the characteristics of Pyle disease.

Dupuytren contracture

MedlinePlus Genetics provides information about Dupuytren contracture

Other Names for This Gene

• frizzled protein, human endometrium
• FRP-4
• FRPHE
• PYL
• secreted frizzled-related protein 4 precursor
• secreted frizzled-related protein 4; secreted frizzled-related protein 4
• sFRP-4

Genomic Location

Normal Function

The WNT4 gene belongs to a family of WNT genes that play critical roles in development before birth. WNT genes provide instructions for making proteins that participate in chemical signaling pathways in the body. These pathways control the activity of certain genes and regulate the interactions between cells during embryonic development.

The WNT4 gene provides instructions for producing a protein that is important for the formation of the female reproductive system, the kidneys, and several hormone-producing glands. During the development of the female reproductive system, the WNT4 protein regulates the formation of the Müllerian ducts, which are structures in the embryo that develop into the uterus, fallopian tubes, cervix, and the upper part of the vagina. This protein is also involved in development of the ovaries, from before birth through adulthood, and is important for development and maintenance of egg cells (oocytes) in the ovaries. In addition, the WNT4 protein regulates the production of male sex hormones (androgens).

Health Conditions Related to Genetic Changes

Müllerian aplasia and hyperandrogenism

At least three mutations in the WNT4 gene have been found to cause Müllerian aplasia and hyperandrogenism, a condition that affects the reproductive system in females. Girls and women with this condition typically have an underdeveloped or absent uterus and do not menstruate. They may also have abnormally high levels of androgens, which can cause acne and excessive facial hair.

WNT4 gene mutations involved in Müllerian aplasia and hyperandrogenism change single protein building blocks (amino acids) in the WNT4 protein. Researchers suspect that the altered protein cannot be released from cells as it normally would be; the trapped protein is unable to perform its usual functions. Loss of regulation by WNT4 likely disrupts development of the female reproductive system and induces abnormal production of androgens, leading to the features of Müllerian aplasia and hyperandrogenism.

Congenital anomalies of kidney and urinary tract

MedlinePlus Genetics provides information about Congenital anomalies of kidney and urinary tract

Dupuytren contracture

MedlinePlus Genetics provides information about Dupuytren contracture

Other disorders

A mutation in the WNT4 gene has been found to cause a severe condition called SERKAL (SEx Reversal and abnormal development of Kidneys, Adrenals, and Lungs) syndrome. In this condition, male sex development may occur despite the chromosome pattern typical of females. SERKAL syndrome has been reported in only one family and likely is not compatible with life. The mutation that causes SERKAL syndrome replaces the protein building block (amino acid) alanine with the amino acid valine at position 114 in the WNT4 protein (written as Ala114Val or A114V). This mutation is present in both copies of the WNT4 gene in each cell and likely eliminates the function of the WNT4 protein. The absence of WNT4 protein results in the wide variety of developmental abnormalities seen in SERKAL syndrome.

A duplication of genetic material in a specific region of chromosome 1 can result in an extra copy of the WNT4 gene. Having an additional copy of this gene leads to the production of extra WNT4 protein. People with this duplication may develop some female features despite having the chromosome pattern typical of males. These individuals can have an underdeveloped uterus and nonfunctional testes.

Other Names for This Gene

• wingless-type MMTV integration site family member 4
• wingless-type MMTV integration site family, member 4
• WNT-4
• WNT-4 protein
• WNT4_HUMAN

Genomic Location

Dupuytren contracture is usually passed down through generations in families and is the most common inherited disorder of connective tissue. The inheritance pattern is often unclear. Some people who inherit gene changes associated with Dupuytren contracture never develop the condition.

In some cases, Dupuytren contracture is not inherited and occurs in people with no history of the condition in their family. These sporadic cases tend to begin later and be less severe than familial cases.

Percutaneous needle fasciotomy has an immediate improvement but a higher recurrence rate and rare tendon, or nerve complications. Collagenase injections require two visits and have an increased number of minor side effects, with rare tendon injuries. Limited fasciectomy removes the diseased tissue and has a prolonged recovery with a higher complication rate, but has the lowest recurrence rate. Secondary fasciectomy after a previous dermofasciectomy has an unexpected amputation rate as high as 8%.

Dupuytren contracture occurs in about 5 percent of people in the United States. The condition is 3 to 10 times more common in people of European descent than in those of non-European descent.