SNP Shot: Genomic Insights

Congenital fiber-type disproportion (CFTD) is a condition affecting primarily skeletal muscles, those used for movement. Individuals with CFTD commonly experience muscle weakness (myopathy), particularly affecting the shoulder, upper arm, hip, and thigh muscles. Facial muscles and those controlling eye movement (ophthalmoplegia) can also be affected, sometimes leading to droopy eyelids (ptosis). Characteristic facial features of individuals with CFTD often include a long face, a high-arched palate, and crowded teeth.

People with CFTD may also develop joint deformities (contractures), an exaggerated inward curve of the lower back (lordosis), or a sideways curvature of the spine (scoliosis). Roughly 30% experience mild to severe breathing difficulties due to weakness in the respiratory muscles. Some require breathing assistance at night using noninvasive mechanical ventilation, and occasionally during the day. Around 30% have swallowing difficulties due to throat muscle weakness. In rare cases, CFTD can result in a weakened and enlarged heart muscle (dilated cardiomyopathy).

The severity of CFTD varies considerably. An estimated 25% experience severe muscle weakness at birth, leading to death in infancy or childhood. Others may only have mild muscle weakness that becomes noticeable in adulthood. More commonly, symptoms appear by age 1, starting with decreased muscle tone (hypotonia) and general muscle weakness. In many instances, muscle weakness does not worsen over time and may even improve. While motor skill development, such as standing and walking, may be delayed, many children with CFTD eventually learn to walk. They often have less stamina compared to their peers but remain active. In rare instances, individuals experience a progressive decline in muscle strength, potentially leading to loss of walking ability and the need for wheelchair assistance.

Inheritance:

CFTD can be inherited in several ways. When caused by mutations in the ACTA1 gene, it typically follows an autosomal dominant pattern. This means only one copy of the mutated gene is sufficient to cause the disorder. Most other cases, including those linked to RYR1 gene mutations, have an autosomal recessive inheritance pattern. In this case, both copies of the gene must be mutated for the condition to develop. Parents of someone with an autosomal recessive condition each carry one mutated gene copy, but usually do not show symptoms. TPM3 gene mutations can cause CFTD via either autosomal dominant or autosomal recessive inheritance.

Rarely, CFTD can be inherited in an X-linked pattern, although the specific gene(s) involved are currently unknown. X-linked inheritance occurs when the mutated gene is located on the X chromosome. In males (who have one X chromosome), only one altered copy is needed to cause the condition. Females (with two X chromosomes) typically experience less severe symptoms or no symptoms at all, as they have a second copy of the X chromosome. A key characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Approximately 40% of individuals with CFTD have a family history of the condition.