Hypochondrogenesis

Hypochondrogenesis

Description

Hypochondrogenesis is one of the group of chondrodysplastic disorders resulting from type II collagenopathy with defects in the gene COL2A1. It is also known as lethal spondyloepiphyseal dysplasia congenita (SED) or achondrogenesis 2-hypochondrogenesis. It is transmitted in a sporadic, probably autosomal dominant fashion although some variants are considered to be of autosomal recessive inheritance. There is a spectrum of disease between achondrogenesis type II, hypochondrogenesis and SED congenita. Clinically and radiographically hypochondrogenesis resembles severe forms of SED but lacks the metaphyseal changes and exhibits the chondro-osseous morphology of achondrogenesis type II. Death usually occurs early in infancy from respiratory insufficiency. This short-trunk, short-limbed dwarfism has a large head, flat face, cleft palate, pear-shaped abdomen and a small thorax.

Diagnosis

The skull shows normal ossification except for a defect behind the foramen magnum. The profile is flattened, the neck is short with redundant soft tissue and the chest is small. The ribs are horizontal and short with anterior cupping. The vertebral bodies are flat and ovoid. The scapula and iliac wings are hypoplastic and the pubic bones are unossified. There is generalized long bone shortening with irregular metaphyses. The femur is short and broad, the hands and feet are small and there is no ossification of the calcaneus and talus.

Differential Diagnosis

Achondrogenesis type II features severe micromelia, lack of mineralization of some or all vertebral bodies and a more significant degree of rib shortening. In SED congenita the degree of long bone shortening is less severe, there are no metaphyseal changes initially, and the rib cage is better developed. In thanatophoric dysplasia there can be a cloverleaf skull (type II), telephone receiver femurs (type I), severe platyspondyly (platyspondylic varieties) and significant bowing of other long bones. The proximal femoral metaphysis is more convex and irregular than that of hypochondrogenesis.

Sonographic Features

Micromelia

Large head with ossified calvarium

Flattened profile

Cleft palate

Small chest

Shortened, horizontal ribs with anterior flaring

Protuberant abdomen

Flattened and ovoid vertebral bodies

Presence of posterior ossification centres

Small scapula and iliac wings

Unossified pubic bones

Short thick long bones with metaphyseal irregularity

Convex distal humeral epiphysis

Small hands and feet with ossified metacarpals, metatarsals and phalanges

Possible cardiac malformations, septal defects

Associated Syndromes 

References

Borochowitz Z, et al Achondrogenesis 2-hypochondrogenesis: variability versus heterogeneity Am J Med Genet 24:273
Maroteaux P, et al Hypochondrogenesis Eur J Pediatr 141:14
Van der Harten HJ, et al Achondrogenesis-hypochondrogenesis:the spectrum of chondrogenesis imperfecta Pediatr Pathol 8:571
Freisinger P, et al Mutation in the COL2A1 gene in a patient with hypochondrogenesis J Biol Chem 269:13663