Guide To The Causes And Risk Factors For Rhabdomyosarcoma

The immature cells that form into muscular cells are referred to as rhabdomyoblasts. When cancer develops in the rhabdomyoblasts in an individual, it is called rhabdomyosarcoma. Rhabdomyosarcoma can develop in any part of the body because voluntary skeletal muscles are abundant and widely distributed, though it forms most commonly in the urinary organs, chest, abdomen, arms, legs, reproductive organs, neck, and head.

Symptoms of rhabdomyosarcoma include eye-bulging, nosebleeds, headache, throat swelling, ear swelling, hematuria, vaginal bleeding, rectal bleeding, and a visible lump in a limb. Rhabdomyosarcoma is diagnosed using a physical examination, blood tests, x-rays, CT scans, PET, bone scans, MRIs, and tissue biopsy. Treatment may include radiation therapy, chemotherapy, and surgery.

Age And Gender

An individual's age and gender can cause them to be at higher risk of developing rhabdomyosarcoma than others. Out of all cases of cancer diagnosed in individuals younger than twenty years old, around seven percent are soft tissue sarcomas. Out of all pediatric childhood soft tissue sarcomas, forty percent are diagnosed with rhabdomyosarcoma. Over half of all cases of rhabdomyosarcoma are diagnosed in individuals under ten years old. Rhabdomyosarcoma is diagnosed in males more often than it is in females.

A correlation has been made that suggests there is a more significant diagnosis ratio gap between males and females when rhabdomyosarcoma is diagnosed in their adolescence versus during their childhood. The only conclusion made regarding the higher rate of male rhabdomyosarcoma diagnosis than females is associated with a general correlation of larger soft tissue mass and volume in males than in females, such as muscle.

Costello Syndrome

A Costello syndrome patient may develop rhabdomyosarcoma as a complication of their genetic disorder. Costello syndrome affects multiple systems around the body and is characterized by loose skin, distinctive facial features, heart problems, weak muscle tone, intellectual disability, abnormally flexible joints, slow growth, and tight tendons. The growth of benign papilloma around the body is a common manifestation of Costello syndrome, along with unusually short stature and decreased levels of growth hormone. Costello syndrome is a disorder that is the result of a mutation on the HRAS gene. This particular gene is what provides the cells with the instructions on how to build a special protein called H-Ras.

H-Ras is an essential component that plays a role in a pathway responsible for the proper control of cell division and cell growth. The type of mutation that occurs in Costello syndrome patients is one that causes the production of an upregulated and overactive form of the H-Ras protein, which causes the cells to divide and grow at a constant rate. This increased cell growth and division causes affected individuals to experience the development of tumors around the body, such as rhabdomyosarcoma.

Beckwith-Wiedemann Syndrome

Beckwith-Wiedemann syndrome is a genetic growth disorder that causes abnormalities in several parts of a patient's body. Common features seen in Beckwith-Wiedemann syndrome are asymmetric growth, larger than normal early childhood statute, abdominal wall birth defect, infant hypoglycemia, abnormally large organs, abnormalities in the kidneys, abnormally large tongue, and skin creases near the ears. There are several different types of genetic mutations that cause Beckwith-Wiedemann syndrome to develop. The affected genes are located on chromosome 11 and include CDKN1C, IGF2, H19, and KCNQ1OT1 genes.

Altered gene regulation is the most common type of mutation that causes this disorder, where the healthy process of gene activation and deactivation at the right time is disrupted or altered in the affected genes. When gene regulation does not function as it should, the body may make more of a certain type of protein and less than another. When the circumstances of altered gene regulation on chromosome 11 effect genes specific to cell growth and division, there is a greater risk of the individual developing rhabdomyosarcoma.

Li-Fraumeni Syndrome

Li-Fraumeni syndrome can cause patients to be at a higher risk of developing rhabdomyosarcoma than healthy individuals. Li-Fraumeni syndrome is a rare genetic disorder where certain gene patterns and alterations cause the individual to be at a very high risk of developing some forms of cancer during their childhood and young adult years. The most common types of cancers that occur in Li-Fraumeni syndrome patients include soft tissue sarcomas, osteosarcoma, brain tumors, adrenocortical carcinoma, leukemias, and breast cancer.

Li-Fraumeni syndrome is caused by mutations in the TP53 and CHEK2 genes. TP53 is a gene that is a part of a group of genes responsible for controlling the division and growth of cells around the body. A problem with the TP53 gene gives cancerous cells a better opportunity to multiply. The CHEK2 gene is also included in the tumor suppressor gene group, making the patient susceptible to cancer growth like rhabdomyosarcoma through the same mechanism.

Neurofibromatosis

Neurofibromatosis patients are at a higher risk of developing rhabdomyosarcoma as a complication of their disorder. Neurofibromatosis is a genetic disorder that affects the cells that make up the nervous system around the body. Common manifestations of neurofibromatosis include patches of light brown skin, bone deformities, hearing loss, neurofibromas, bone enlargement, scoliosis, and learning disabilities. Neurofibromatosis is caused by mutations in certain genes passed down from a patient's parents in most cases.

The mutation that causes neurofibromatosis that occurs on the NF1 gene on chromosome 17 promotes the uncontrolled growth of cells around the body as a result of a deficiency of neurofibromin. The causative mutation that occurs on the NF2 gene on chromosome 22 promotes uncontrolled cell growth in tissues by decreasing the amount of a protein called merlin. The causative mutation that may occur on the SMARCB1 and LZTR1 genes also promotes cell proliferation by reducing the amount of other tumor-suppressing proteins. It is the cell proliferation that occurs in close proximity to soft tissues that cause the development of soft tissue cancers like rhabdomyosarcoma.