SNP Shot: Genomic Insights

Achondroplasia is the most prevalent type of dwarfism characterized by shortened limbs. The term "achondroplasia" literally translates to "without cartilage formation." Cartilage, a resilient yet pliable tissue, forms a significant portion of the skeleton during the early stages of development. However, in individuals with achondroplasia, the primary issue isn't the formation of cartilage itself, but rather the process of its conversion into bone, known as ossification. This is particularly evident in the long bones of the arms and legs. Achondroplasia shares similarities with hypochondroplasia, another skeletal disorder, but achondroplasia generally presents with more pronounced features.

A consistent characteristic of achondroplasia is short stature. Without medical intervention, adult males with achondroplasia typically reach an average height of 131 centimeters (4 feet, 4 inches), while adult females average 124 centimeters (4 feet, 1 inch). Other defining features include a torso of average size, shortened arms and legs (especially the upper arms and thighs), limited elbow mobility, and an enlarged head (macrocephaly) with a prominent forehead. The fingers are usually short, and the ring and middle fingers may separate, giving the hand a distinctive three-pronged or "trident" appearance.

Common health issues associated with achondroplasia include obesity and recurring ear infections. Individuals with achondroplasia typically have normal intelligence. During childhood, they often develop a noticeable and permanent curvature of the lower back (lordosis) and bowed legs. Some individuals may also experience abnormal curvature of the spine from front to back (kyphosis) and associated back pain.

As individuals with achondroplasia get older, they may face a potentially serious complication called spinal stenosis. This condition involves a narrowing of the spinal canal, which can compress the upper portion of the spinal cord. Spinal stenosis can lead to pain, tingling, and weakness in the legs, making walking difficult. In rare but severe cases during early childhood, stenosis of the foramen magnum (the opening at the base of the skull where the spinal cord exits) can occur. This can compress the brain stem, leading to pauses in breathing during sleep (sleep apnea) or hydrocephalus. Hydrocephalus is a buildup of fluid in the brain, which can cause increased head size and related brain abnormalities.

Inheritance:

Achondroplasia follows an autosomal dominant inheritance pattern. This means that only one copy of the altered gene in each cell is enough to cause the disorder. Approximately 80% of individuals with achondroplasia are born to parents without the condition and of average height; these instances arise from new mutations in the FGFR3 gene. In the remaining cases, individuals with achondroplasia inherit a mutated FGFR3 gene from one or both affected parents. Individuals inheriting two mutated copies of the FGFR3 gene typically have a severe form of achondroplasia, leading to extreme bone shortening and an underdeveloped rib cage. These individuals are usually stillborn or die shortly after birth due to respiratory failure.