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.
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.
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.
Large head with ossified calvarium
Shortened, horizontal ribs with anterior flaring
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
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