SNP Shot: Genomic Insights

Craniometaphyseal dysplasia is an uncommon disorder marked by excessive bone thickening (hyperostosis), primarily affecting the skull (cranium) and the metaphyses, which are the ends of long bones. This abnormal bone formation is progressive, continuing throughout life. Generally, the life expectancy of individuals with craniometaphyseal dysplasia is typical, except in the most severe manifestations.

Many of the symptoms of craniometaphyseal dysplasia stem from the overgrowth of bone in the head. Common facial characteristics include a broadened nasal bridge, a prominent forehead, widely spaced eyes (hypertelorism), and a noticeable jaw. Excessive bone in the jaw can lead to delayed or absent tooth eruption. Infants with the condition might experience breathing difficulties or feeding problems due to constricted nasal passages. In severe instances, the bone overgrowth can compress cranial nerves, which extend from the brain to the head and neck. This compression can cause facial paralysis (facial nerve palsy), vision loss, or hearing impairment.

X-ray imaging reveals that individuals with craniometaphyseal dysplasia have abnormally shaped long bones, particularly in the legs. The ends of these bones are broadened and appear less dense compared to healthy individuals.

Craniometaphyseal dysplasia is categorized into two types based on their inheritance pattern and underlying genetic cause: autosomal dominant and autosomal recessive.

Inheritance:

When caused by variations in the *ANKH* gene, craniometaphyseal dysplasia follows an autosomal dominant inheritance pattern. This means that only one altered copy of the *ANKH* gene in each cell is sufficient to cause the condition. Typically, individuals with the autosomal dominant form inherit the mutated gene from a parent who also has the condition. However, in some cases, the condition arises from a new (de novo) gene mutation in individuals with no family history of the disorder. When caused by variants in the *GJA1* gene, craniometaphyseal dysplasia demonstrates an autosomal recessive inheritance pattern. This requires that both copies of the *GJA1* gene in each cell be altered for the condition to manifest. In autosomal recessive cases, both parents are carriers of one copy of the altered gene, but they usually do not exhibit symptoms of the disorder themselves.