Undersulphation has a pronounced effect on the composition of the extracellular matrix of cartilage, and this has been shown by the physical, biochemical, and histological findings.
Histologic findings include rarefied cartilage matrix, loss of normal ground glass appearance of cartilage on HE staining, coarse collagen fibres and collagen rings.
Achondrogenesis 1B is thought to carry an autosomal recessive inheritance. Point mutations and deletions of the diastrophic dysplasia sulphatase transporter (DTDST) gene it thought to be the underlying factor. This is located on chromosome 5q and is responsible for sulphate transport. The mutation results in impaired activity of the sulphate transporter in chondrocytes and fibroblasts and results in the synthesis of proteoglycans which are not sulphated or only insufficiently sulphated (probably by depletion of intracellular sulphate).
The fetuses frequently present in breech position. The physical appearance is strikingly abnormal and which includes flat face, narrow thorax with protuberant abdomen, and particularly the severe micromelia with short stubby fingers and toes. Stillbirth is common.
- severely hypoplastic skeleton
- the skull is mildly affected and is slightly less ossified than expected for gestational age, and the orbits may be extended laterally and superiorly
- clavicles are short or normal size
- the scapulae are small with irregular contour
- the ribs are slightly thinner and much shorter than normal with cupping of distal ends
- the iliac bones are smaller than usual and only their upper half is irregularly ossified
- there is severe shortening and metaphyseal spurring of long bones
- ulna and fibula are not ossified in most of the cases
- short bones of hands and feet are very poorly ossified and sometimes there is bipartite ossification of medial phalanges can be seen
Treatment and prognosis
Infants are either stillborn or die shortly after birth. Genetic counselling and prenatal diagnosis are useful for such cases as this disorder is inherited as autosomal recessive traits. For a given couple, the chance of future children having the condition is 25%, with a 50% chance of being asymptomatic carriers and 25% chance of being unaffected.
- 1. Superti-Furga A. Achondrogenesis type 1B. J. Med. Genet. 1996;33 (11): 957-61. doi:10.1136/jmg.33.11.957 - Free text at pubmed - Pubmed citation
- 2. Jones KL, Jones MC, del Campo M. Smith's Recognizable Patterns of Human Malformation. Elsevier Health Sciences. (2013) ISBN:0323186688. Read it at Google Books - Find it at Amazon