Achondrogenesis type 2

A rare genetic disorder affecting bone development

Achondrogenesis type 2 is a rare genetic disorder characterized by severe dwarfism due to abnormal bone development. It is one of the most severe forms of skeletal dysplasia and is typically lethal in the perinatal period.

Genetics

Achondrogenesis type 2 is caused by mutations in the COL2A1 gene, which encodes the alpha-1 chain of type II collagen. This gene is crucial for the normal development of cartilage and bone. The disorder follows an autosomal dominant pattern of inheritance, meaning a single copy of the mutated gene can cause the disorder.

Diagram showing autosomal dominant inheritance pattern

Pathophysiology

The mutation in the COL2A1 gene leads to defective type II collagen, which is essential for the normal formation of cartilage. This defect results in the impaired development of the skeletal system, leading to the characteristic features of achondrogenesis type 2. The cartilage is unable to properly ossify into bone, leading to severely shortened limbs and other skeletal abnormalities.

Clinical Features

Individuals with achondrogenesis type 2 typically present with:

• Severe short stature
• Disproportionately short limbs
• A small thorax
• Hydrops fetalis
• Polyhydramnios during pregnancy
• Micrognathia
• Macrocephaly

Diagnosis

Diagnosis of achondrogenesis type 2 is often made prenatally through ultrasound findings of severe skeletal abnormalities. Postnatal diagnosis can be confirmed through radiographic imaging and genetic testing to identify mutations in the COL2A1 gene.

Management

There is currently no cure for achondrogenesis type 2. Management is supportive and focuses on addressing the symptoms and complications associated with the disorder. Due to the severe nature of the condition, most affected individuals do not survive beyond the neonatal period.

Related pages

• Skeletal dysplasia
• Collagen
• Genetic disorder
• Dwarfism

Gallery

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  Diagram showing autosomal dominant inheritance pattern