Acheiropodia, also known as Horn Kolb syndrome, is a genetic condition that affects limb development, resulting in shortened arms and legs and absent hands and feet on both sides of the body at birth. Specifically, individuals are born missing the epiphysis typically found at the end of the humerus bone of the upper arm, the diaphysis which makes up the long section of the tibia bone of the shin, the radius and ulna bones which make up the lower arm, the fibula bone of the shin, and all hand and foot bones.
Discovery and prevalence
Acheiropodia was first described in Brazil in 1929 and the variations in expression (the range in severity and type of signs and symptoms experienced by patients), namely the presence or absence of digits on upper limbs or the Bohomeletz bone (a small, elongated bone located at the upper limb tips, parallel to the humerus and suggested to be what would have developed into the ulna), were further documented in 1930. It was noted that the presence of one or more digits on upper limbs was consistently associated with the absence of the Bohomeletz bone, and when the Bohomeletz bone was attached, digits were absent from the residual limbs. It was estimated that there were 3 cases of acheiropodia for every 10 million people. When there is no functional protein present, limb development does not occur correctly, and individuals are born with acheiropodia.
thumb|467x467px|The rare variant in C7rof2 results in the processed RNA transcript missing exon 4. As a result, the [[translation (biology)|conversion from RNA to protein is halted early, resulting in a short, nonfunctional protein. Two mutated copies of the gene, leading to two nonfunctional proteins, are required for acheiropodia to develop.|center]]
The C7rof2 DNA sequence is very stable and changes occur rarely, partly explaining the rarity of this condition.|500x500px]]In Acheiropodia, 12,000 letters of DNA are removed, eliminating three CCCTC-binding factor (CTCF) sites. When the ZRS enhancer can interact with the SHH promoter, there is increased expression of the SHH protein. However, in the case of acheiropodia, the 3 CTCF sites are missing, which prevents ZRS from interacting with the SHH promoter. Fingers are sometimes present, and a small bone at the tip of the shortened limb (the Bohomoletz bone) may or may not be present. although research on similar conditions suggests it may be diagnosed even earlier. If ultrasound screening indicates possible acheiropodia, further (more invasive) testing may be performed, including genetic analysis of either an amniotic fluid sample or placenta (chorionic villus) sample to confirm diagnosis. In the case of fetal death or termination, autopsy findings may conclude in a diagnosis. Surgery may be considered on a case-by-case basis to optimize prosthetic fitting. Some children may adapt with compensatory skills that are more effective than prostheses.
Challenges with studying
Acheiropodia has proven to be challenging for researchers to study. Mice often serve as a model system to study human disease due to their similar physiology and genetics. However, it was previously observed that when the 12,000 letters of DNA in the mouse equivalent of the C7rof2 human gene were removed, limbs developed normally.