Liebenberg syndrome

Liebenberg syndrome
Classification and external resources
OMIM	186550
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Liebenberg Syndrome is a rare autosomal genetic disease that involves a deletion mutation upstream of the PITX1 gene, which is one that's responsible for the body's organization, specifically in forming lower limbs. In animal studies, when this deletion was introduced to developing birds, their wing buds were noted to take on limb-like structures. People who are affected by Liebenberg Syndrome suffer from three main symptoms:

The condition was first described by Dr. F. Liebenberg in 1973 while he followed multiple generations of a South African family, but it has since been noticed in other family lineages across the world.

Liebenberg Syndrome follows an autosomal dominant mode of inheritance, whereby heterozygotes with this mutation express the disease phenotype.

It is caused by a heterozygous mutation to chromosome 5. It involves the inappropriate enhancement of the PITX1 gene due to genetic deletions and chromosome translocations.

PITX1 is a homeobox gene which are genes that regulate proper body structure development. This PT1X gene encodes a transcription factor expressed in hind limbs. When expressed, it causes the formation of hindlimb structures.

Liebenberg Syndrome is a result of one of two different genetic mutations. The first is a deletion upstream of the PITX1 gene on chromosome 5. This deletion includes the H2AFY gene, which is responsible for suppressing an upstream enhancer element known as hs1473. When H2AFY is removed, the enhancer is brought closer to PITX1 and inappropriately enhances it in forelimbs, causing them to adopt hindlimb morphology.

The second mutation that can cause the phenotype for Liebenberg syndrome is a translocation of chromosome 18 and chromosome 5. Translocation mutations are ones that switch parts of non-homologous chromosomes with each other. This move introduces two enhancers from chromosome 18 to move to a position directly upstream of PITX1 on chromosome 5. The enhancers increase transcription of the PITX1 gene and cause patients to develop the same phenotype described above.

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