Fibrochondrogenesis
Fibrochondrogenesis is a severe, rare disorder of bone growth characterized by short stature, distinctive facial features, and skeletal abnormalities that often lead to respiratory failure in infancy.
Overview
Fibrochondrogenesis is a very severe bone growth disorder. Affected infants typically have a narrow chest that prevents normal lung development, often resulting in stillbirth or death shortly after birth due to respiratory failure. However, some individuals have survived into childhood.
Symptoms
The condition is characterized by dwarfism and specific skeletal abnormalities, including:
- Shortened long bones in the arms and legs that are unusually wide at the ends (dumbbell-shaped).
- A narrow chest with short, wide ribs.
- A round and prominent abdomen.
- Flattened vertebrae (platyspondyly) with a pinched or pear-shaped appearance.
- Underdeveloped hip (pelvic) bones.
Distinctive facial features include a flat-appearing midface, low-set ears, a small chin, and a nose with a flat bridge and nostrils that open to the front. Survivors may experience vision problems, such as severe nearsightedness (myopia) and clouding of the lens (cataracts), as well as sensorineural hearing loss.
Causes
Fibrochondrogenesis results from mutations in the COL11A1 (Type 1) or COL11A2 (Type 2) genes. These genes provide instructions for making components of type XI collagen, a molecule that provides structure and strength to cartilage and other connective tissues. Mutations impair the assembly of this collagen, weakening connective tissues and disrupting skeletal formation.
Inheritance
This condition is generally inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell have mutations. Parents of an affected individual typically carry one copy of the mutated gene without showing symptoms. In rare cases, COL11A2 mutations have been inherited in an autosomal dominant pattern, resulting from a new (de novo) mutation.