Liebenberg syndrome

Alternate names

Liebenberg syndrome; brachydactyly with joint dysplasia; carpal synostosis with dysplastic elbow joints and brachydactyly

Definition

Liebenberg syndrome is a condition that involves abnormal development of the arms, resulting in characteristic arm malformations that can vary in severity.

Epidemiology

Liebenberg syndrome is a rare condition. Fewer than 10 affected families have been described in the medical literature.

Cause

• Liebenberg syndrome is caused by genetic changes near the PITX1 gene.
• The protein produced from this gene plays a critical role in lower limb development by controlling the activity of other genes involved in limb development, directing the shape and structure of bones and other tissues in the legs and feet.

Gene mutations

• The genetic changes involved in Liebenberg syndrome delete, insert, or rearrange genetic material near the PITX1 gene.
• These changes affect regions of DNA known as regulatory elements, which help turn on or turn off genes (known as enhancers or repressors, respectively).
• They control when and where certain genes are active.
• The mutations that cause Liebenberg syndrome are thought to relocate enhancers that normally promote the activity of genes involved in upper limb development to be near the PITX1 gene, where they can promote its activity.
• Alternatively, the mutations may remove repressors that normally turn off the PITX1 gene during upper limb development.
• As a result, the PITX1 gene is abnormally active during development of the upper limbs.
• Because the PITX1 protein normally directs lower limb structure, bones, muscles, and tendons in the arms and hands develop more like those in the legs and feet, leading to the features of Liebenberg syndrome.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

Liebenberg syndrome is inherited in an autosomal dominant pattern, which means having a genetic change that affects the PITX1 gene on one copy of the chromosome in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.

Signs and symptoms

• In people with this condition, bones and other tissues in the elbows, forearms, wrists, and hands have characteristics of related structures in the lower limbs.
• For example, bones in the elbows are abnormally shaped, which affects mobility of the joints.
• The stiff elbows function more like knees, unable to rotate as freely as elbows normally do.
• Bones in the wrists are joined together (fused), forming structures that resemble those in the ankles and heels and causing permanent bending of the hand toward the thumb (radial deviation).
• The bones in the hands (metacarpals) are longer than normal, and the fingers are short (brachydactyly), similar to the proportions of bones found in the feet.
• In addition, muscles and tendons that are typically found only in the hands and not in the feet are missing in people with Liebenberg syndrome.
• Affected individuals also have joint deformities (contractures) that limit movement of the elbows, wrists, and hands. Development of the lower limbs is normal in people with this condition.
• Individuals with Liebenberg syndrome have no other health problems related to this condition, and life expectancy is normal.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Abnormal distal phalanx morphology of finger(Abnormality of the outermost finger bone)
• Abnormal fingernail morphology(Abnormal fingernails)
• Abnormality of the humerus
• Abnormality of the ulna
• Aplasia/Hypoplasia of the radius
• Brachydactyly(Short fingers or toes)
• Clinodactyly of the 5th finger(Permanent curving of the pinkie finger)
• Elbow dislocation(Dislocations of the elbows)
• Joint stiffness(Stiff joint)
• Macrocephaly(Increased size of skull)
• Synostosis of carpal bones(Fusion of wrist bones)

Diagnosis

Molecular Genetics Tests includeː

• Deletion/duplication analysis
• Targeted variant analysis
• Sequence analysis of the entire coding region

Treatment

• Surgery is an option to correct some of the morphological changes made by Liebenberg Syndrome.
• Cases exist where surgery is performed to correct radial deviations and flexion deformities in the wrist.
• A surgery called a carpectomy has been performed on a patient whereby a surgeon removes the proximal row of the carpal bones.
• This procedure removes some of the carpal bones to create a more regular wrist function than is observed in people with this condition.

NIH genetic and rare disease info

• NIH info on Liebenberg syndrome

Liebenberg syndrome is a rare disease.

Liebenberg syndrome Resources
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