Achondrogenesis 1B

The Parenti-Fraccaro sub typesubtype or Achondrogenesisachondrogenesis type Ib is a sub typesubtype of achondrogenesis. It is an extremlyextremely rare skeletal dysplasia (chondrodysplasia). 

or is a rare autosomal recessive disorder of chondrodysplasias.

Pathology

Undersulphation has a pronounced effect on the composition of the extracellular matrix of cartilage, and this has been shown 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 collegencollagen fibres and collagen rings.

Genetics

It is though to carry an autosominalautosomal recessive inheritenceinheritance.Point Point mutations and deletions of the diastrophic dysplasia sulfatasesulphatase 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 results in the synthesis of proteoglycans which are not sulphated or only insufficiently suphatedsulphated (probably by depletion of intracellular sulphate).

Clinical presentation

The fatusesfetuses 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 micronmeliamicromelia with short stubby finigersfingers and toes. Stillbirth is common.

Radiographic features

Features include:

• severely hypoplastic skeleton.
• the skull is mildly affected and 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 Metaphysealmetaphyseal 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 sometime 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 recurrence risk is 25% which is quite significant, 50% chance of being an asymptomatic carriers and 25% chance of being unaffected  unaffected.