Achondrogenesis
Achondrogenesis Definition
Marco Fraccaro was the very first person to observe and record the description of achondrogenesis in the year 1952. Fraccaro used this name in description of a stillborn female who was afflicted with acute micromelia and apparent changes on her histological cartilage. This term was then coined to characterize many more acute kinds of chondrodysplasia among humans. The conditions were invariably lethal on pre and post births. When the 70's came, researchers have concluded that the disorder is a part of a heterogenous cluster of chondrodysplasias that are fatal to neonates. Histological and radiological measures have distinguished the achondrogenesis type 1 (which is the Fraccaro-Houston-Harris kind) and the type 2 (or the Langer-Saldino kind). 1983 marked a new radiological category of the disease (Types 1-4). This was done by Gorlin and Whitley and was adapted by the McKusick catalog. This classification describes types 1 and 2 as having similar femoral cylinder indeces (or Clfemur which is calculated as the length of the femur bone divided by the range of the width of the same bone. Both kinds have stellate elongated bones and crenated ilia. Both types 1 and 2 are characterized by several rib fractures. Type 3 has ribs that are non-fractured, mushroom-stemmed elongated bones, halberd ilia, and a Clfemur 2.8 to 4.9. The last type (type 4) has sculpted ilia, long bones that are well-developed, non-fractured ribs and Clfemur measured at 4.9 to 8.0. The late 80's was the time when mutations on the collagen II structure were depicted to cause achondrogenesis type 3 (which might also correspond to type 2). At present, only 3 variants of the disorder have been identified and they are type IA or the Houston-Harris type; type IB (or the Parenti-Fraccaro type); and type II (or the Langer-Saldino type).
Achondrogenesis Frequency
Types 1 and 2 (the lethal types of achondrogenesis) are very rare. Their exact frequencies are still unknown but the general frequency is estimated at 1 in every 40,000 babies that are born.
Achondrogenesis Pathophysiology
Mutation series of the DDST gene have been observed in achondrogenesis type IB patients. Compound heterozygosity or homozygosity for the mutations is associated with achodrogenesis type IB. Mutations of the cytoplasmic tail, low levels of mRNA (low messenger RNA), or extracellular loops often result into atelosteogenesis type 2 or the so-called diastrophic dysplasia (with less acute phenotypes). Type 2 has a sole base alteration, where glycine is substituted for serine in the type 2 genetic procollagen of the alpha 1 (II) chain. This causes disruption of the triple helix structure which leads to type 2 collagen paucity in the cartilage matrix. Type 2 hypochondrogenesis or achondrogenesis has immunohistologic results which demonstrate defective intracellular buildup of type 2 collagen contained by vacuolar makeup of chondrocytes.