Atelosteogenesis- type 1

Synonyms

3

Overview

Atelosteogenesis type 1 (AO I) is a disorder that affects the development of bones throughout the body. Affected individuals are born with inward- and upward-turning feet (clubfeet) and dislocations of the hips, knees, and elbows. Bones in the spine, rib cage, pelvis, and limbs may be underdeveloped or in some cases absent. As a result of the limb bone abnormalities, individuals with this condition have very short arms and legs. Characteristic facial features include a prominent forehead, wide-set eyes (hypertelorism), an upturned nose with a grooved tip, and a very small lower jaw and chin (micrognathia). Affected individuals may also have an opening in the roof of the mouth (a cleft palate). Males with this condition can have undescended testes.

Individuals with atelosteogenesis type 1 typically have an underdeveloped rib cage that affects the development and functioning of the lungs. As a result, affected individuals are usually stillborn or die shortly after birth from respiratory failure.

Symptoms

  • Short stature
  • Proximal limb shortness
  • Short humeri
  • Absent fibula
  • Short femora
  • Rounded proximal end of femora
  • Squared and tapered distal end of femora
  • Abnormally segmented neck vertebrae
  • Fused neck vertebrae
  • Thoracic platyspondyly
  • Multiple thoracic coronal clefts
  • Eleven pairs of ribs
  • Narrow thoracic cage
  • Delayed ossification of first two bone sections of fingers
  • Delayed ossification of first two bone sections of toes
  • Polyhydramnios
  • Depressed nasal bridge

Causes

Mutations in the FLNB gene cause atelosteogenesis type 1. The FLNB gene provides instructions for making a protein called filamin B. This protein helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Filamin B attaches (binds) to another protein called actin and helps the actin to form the branching network of filaments that makes up the cytoskeleton. Filamin B also links actin to many other proteins to perform various functions within the cell, including the cell signaling that helps determine how the cytoskeleton will change as tissues grow and take shape during development.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Almost all cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Diagnosis

The inutero diagnosis of atelosteogenesis is unusual. The diagnosis is based primarily on the radiographic appearance of the spine, long bones and hands and histopathologic study of the growth cartilage.

Resources

  • Genetics Home Reference