Acheiropodia
 | This article needs additional citations for verification. (August 2020) |
| Acheiropodia | |
|---|---|
| Other names | Horn-Kolb syndrome, acheiropody and aleijadinhos (Brazilian type) |
 | |
| Acheiropodia has an autosomal recessive pattern of inheritance | |
| Specialty | Medical genetics  |
Acheiropodia, also known as Horn Kolb syndrome,[1] 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.[2] 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.[2] It was first discovered and is prevalent almost exclusively in Brazil.[3]
Genetics
Acheiropodia results from a change in the DNA sequence of the C7rof2 gene.[4] When this altered DNA is transcribed to RNA, the resulting RNA transcript is processed differently from unaltered RNA. A segment of the processed RNA transcript called exon 4, which codes for a segment of the protein, is missing, causing the process of converting the transcript into a protein to stop too early.[4] This leads to a shorter, non-functional protein.
The C7rof2 gene is the human equivalent of the mouse gene
The C7rof2 DNA sequence is very stable and changes occur rarely, partly explaining the rarity of this condition.[5] Since the rare gene copy is unlikely to be found in parents from two unrelated families, acheiropodia is often caused by consanguineous marriages in which genetically related individuals have children together.[4]
Diagnosis
The rarity and subsequent lack of information on acheiropodia makes prenatal diagnosis difficult. Diagnosis depends on prenatal ultrasound screening, with a failure to visualize bones at the ends of fetal limbs.[1] Due to variable expressivity of the C7rof2 gene, acheiropodia presents differently among affected individuals, adding to the difficulty of diagnosis.[6] Fingers are sometimes present, and a small bone at the tip of the shortened limb (the Bohomoletz bone) may or may not be present.[6]
Acheiropodia has been diagnosed at as early as 16 weeks post-conception,[7] although research on similar conditions suggests it may be diagnosed even earlier.[8] If ultrasound screening indicates possible acheiropodia, further (more invasive) testing may be performed,[9] including genetic analysis of either an amniotic fluid sample or placenta (chorionic villus) sample to confirm diagnosis.[9][10] In the case of fetal death or termination, autopsy findings may conclude in a diagnosis.[9]
Treatment
Even with early prenatal diagnosis, due to its genetic basis acheiropodia cannot currently be prevented or cured. However, once a child is born with acheiropodia, prosthetics could improve their quality of life.[11] Surgery may be considered on a case-by-case basis to optimize prosthetic fitting.[11] Prosthetic fitting should occur before 2 years of age to minimize the risk of rejection.[11] Ideally, fitting should begin around the 6-9 month mark, when healthy infants typically begin using their hands and feet to stand and handle objects.[11] Even without prosthetics, many children with limb loss learn to functionally use their residual limbs.[12] A multidisciplinary approach may best treat the medical, psychological, and developmental challenges that may occur in infants missing all four limbs.[13]