ACHONDROPLASIA

Achondroplasia, a nonlethal form of chondrodysplasia, is the most common form of short limb dwarfism. It is inherited as a Mendelian autosomal dominant trait with complete Penetrance.

It is caused by mutation in the fibroblast growth factor receptor 3 (FGFR3) gene, this is the only gene know to cause Achondroplasia; it has been mapped to chromosome 4, band p16.3.

The mutation cause an increased function of the FGFR3 gene, resulting in decreased endochondral ossification, inhibited proliferation of chondrocytes in growth plate cartilage, decreased cellular hypertrophy, and decreased cartilage matrix production.

Mortality/Morbidity.

Sudden death within the first year of life is attributed to abnormalities at the craniocervical junctions causing spinal cord compression.

Respiratory disorders are seen frequently.

Severe upper airway obstruction occurs in less than 5% in children with Achondroplasia.

Normal life span and fertility.

Neurologic findings.

Hypotonia in infancy and early childhood.

Delayed motor milestones.

Normal intelligence with possible minor deficit in visual-spatial tasks.

Craniofacial feature.

Large calvarial bones in contrast to the small cranial base and facial bones.

True megalencephaly (large head) with frontal bossing.

Midface hypoplasia.

Dental malocclusion and crowding.

Skeletal features.

Disproportionate short stature.

Normal trunk length that appears long and narrow, small thoracic cage.

Rhizomelic shortening of the proximal limbs with redundant skin folds.

Brachydactyly and trident hand configuration.

Thoracolumbar gibbus in infancy, which is replaced by an exaggerated lumbar lordosis once ambulation begins.

Hyperextensibility of most joints (knee).

Limited elbow extension and rotation.

Genu varum (bow legs).

Causes.

Advance paternal age is identified as a risk factor in de novo cases of Achondroplasia , suggesting that factors influencing DNA replication or repair during the spermatogenesis may predispose men to the occurrence of G1138   FGFR3  mutations.

DDx.

Achondrogenesis

Asphyxiating Thoracic Dystrophy (Jeune syndrome).

Hypochondroplasia.

SADDAN Dysplasia.

Skeletal Dysplasia

Thanotophoric Dysplasia.

Laboratory studies.

Direct DNA analysis of FGFR3 mutations identifies the G1138 mutation in patients with Achondroplasia, and a novel missense mutation (Lys650Met) in tyrosine kinase.

Imaging studies: radiography, MRI, ultrasonography.