SNP Shot: Genomic Insights

Metatropic dysplasia is a skeletal disorder that causes dwarfism, or short stature, alongside other skeletal abnormalities. Its name, derived from the Greek "metatropos" meaning "changing patterns," reflects the way the condition's skeletal features evolve over time.

Infants with metatropic dysplasia typically present with a narrow chest and disproportionately short arms and legs, with long bones shaped like dumbbells. As they enter early childhood, they develop scoliosis and kyphosis (kyphoscoliosis), abnormal curvatures of the spine that worsen over time and are difficult to treat. This severe kyphoscoliosis can lead to a significantly shortened torso relative to the limbs.

Some individuals with metatropic dysplasia are born with a coccygeal tail, an elongated tailbone made of cartilage that usually shrinks over time. Additional skeletal issues may include flattened vertebrae (platyspondyly); excessive spinal movement in the neck, potentially damaging the spinal cord; either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum); and joint contractures, which limit movement in the shoulders, elbows, hips, and knees. Furthermore, a degenerative form of arthritis often develops early in life, causing joint pain and further limiting mobility.

The severity of metatropic dysplasia varies significantly, ranging from mild to life-threatening. In severe cases, a constricted chest and spinal deformities impede proper lung expansion, leading to breathing difficulties. Previously, researchers categorized metatropic dysplasia into distinct types (mild, classic, and lethal) based on the severity of symptoms. However, current understanding recognizes these as part of a single condition with a spectrum of overlapping features.

Inheritance:

Metatropic dysplasia is an autosomal dominant disorder, meaning that only one mutated copy of the TRPV4 gene in each cell is sufficient to cause the condition. The majority of cases result from new mutations in the gene, occurring in individuals with no family history of the disorder. In rare instances, the condition is inherited from an affected parent. While the lethal type was once thought to be autosomal recessive (requiring two mutated copies), current research confirms that all forms of metatropic dysplasia follow an autosomal dominant inheritance pattern.