Marfan Syndrome is a genetic disorder impacting the body’s connective tissue, which provides support, strength, and flexibility. This tissue is found throughout the body, playing a role in growth and development. Because connective tissue is widespread, Marfan Syndrome can affect many body systems, including the heart, blood vessels, bones, joints, eyes, and lungs.
Characteristic Tall Stature in Marfan Syndrome
Individuals with Marfan Syndrome often exhibit a tall and slender build, generally exceeding the average height for the general population. This characteristic tall stature becomes apparent after the second year of life, with affected individuals typically being approximately 10 cm taller than their peers by age two. Studies indicate that the mean height for individuals with Marfan Syndrome can be 4-10 cm above the population average, with the 50th percentile for height in Marfan patients often surpassing the 97th percentile of normative growth curves for both sexes.
The underlying reason for this increased height is directly linked to the defective connective tissue. Marfan Syndrome is caused by mutations in the FBN1 gene, which provides instructions for making fibrillin-1, a protein that forms microfibrils, a component of connective tissue. These microfibrils are important for the structural integrity of tissues and also help regulate growth factors.
Specifically, fibrillin-1 normally sequesters transforming growth factor-beta (TGF-β), thereby limiting its activity. In Marfan Syndrome, defective fibrillin-1 leads to insufficient sequestration of TGF-β, resulting in elevated levels of this growth factor. This increased TGF-β signaling promotes excessive growth of long bones, contributing to the characteristic tall stature observed in these individuals.
Disproportionate Body Proportions
Beyond simply being tall, individuals with Marfan Syndrome frequently display distinct body disproportions that are important diagnostic indicators. One common feature is an arm span that significantly exceeds body height, often by at least 5 cm, or an arm span-to-height ratio greater than 1.05. This measurement reflects the elongated limbs characteristic of the syndrome.
Another key disproportion is a reduced upper-to-lower segment ratio. The upper segment is measured from the top of the head to the pubic symphysis, while the lower segment extends from the pubic symphysis to the floor. In individuals with Marfan Syndrome, the lower body segment is typically longer than the upper body segment, resulting in a ratio less than 0.85. Fingers and toes also tend to be unusually long and slender, a condition known as arachnodactyly, often described as “spider fingers”. Specific clinical tests, such as the Steinberg thumb sign (where the thumb extends beyond the ulnar border of the palm when clasped in a clenched fist) and the Walker-Murdoch wrist sign (where the thumb and fifth finger overlap when encircling the opposite wrist), are used to identify these disproportionate limb lengths and digits.
Genetic Influence on Height and Growth
The skeletal manifestations, including increased height and disproportionate limb lengths, stem from mutations in the FBN1 gene located on chromosome 15. This gene is responsible for producing fibrillin-1, a glycoprotein that is a major component of microfibrils within the extracellular matrix. These microfibrils provide structural support and elasticity to connective tissues throughout the body. Mutations in the FBN1 gene lead to a deficiency or dysfunction of fibrillin-1, compromising the integrity of connective tissues. This genetic defect ultimately results in the characteristic overgrowth of long bones and the elongated limbs observed in Marfan Syndrome.
Monitoring and Clinical Management of Growth
Monitoring height and growth patterns is an important aspect of clinical management for individuals with Marfan Syndrome. Regular measurements are taken and often plotted on disease-specific growth charts, which account for the typical growth patterns seen in Marfan patients, as standard growth charts may not accurately reflect their unique trajectory. These specialized charts help clinicians track growth, predict adult height, and assess responses to any growth-modifying therapies.
In cases where excessive height is predicted to cause significant complications or concerns, medical interventions may be considered. One approach involves hormone therapies, such as administering sex hormones like estrogen to girls. These treatments aim to accelerate epiphyseal plate closure, thereby shortening the pubertal growth spurt and limiting final adult height.
Studies suggest that initiating estrogen therapy before age 10.5 or 11 years can be more effective in reducing predicted adult height. Another potential intervention is epiphysiodesis, an orthopedic surgical technique that involves operating on the knee growth plates to stop further bone growth. This minimally invasive procedure is most effective when performed early in puberty.