About jarcho levin syndrome
What is jarcho levin syndrome?
Jarcho-Levin syndrome is a rare genetic disorder characterized by distinctive malformations of bones of the spinal column (vertebrae) and the ribs, respiratory insufficiency, and/or other abnormalities. Infants born with Jarcho-Levin syndrome have short necks, limited neck motion due to abnormalities of the cervical vertebrae and short stature.
In most cases, infants with Jarcho-Levin syndrome experience respiratory insufficiency and are prone to repeated respiratory infections (pneumonia) that result in life-threatening complications. The vertebrae are fused and the ribs fail to develop properly, therefore, the chest cavity is too small to accommodate the growing lungs.
There are apparently two forms of Jarcho-Levin Syndrome that are inherited as autosomal recessive genetic traits and termed spondylocostal dysostosis type 1 (SCDO1) and spondylocostal dyostosis type 2 (SCDO2).
What are the symptoms for jarcho levin syndrome?
The signs and symptoms of spondylocostal dysplasia can vary greatly from one person to another, even among members of the same family. Affected individuals have abnormalities in the development of the spine and ribs.
The bones of the spine (vertebrae) may be fused together or misshapen. Sometimes, they are underdeveloped and wedge-shaped (hemivertebrae). Multiple vertebrae are always affected, usually at least 10 segments in a row (contiguously). The ribs may be fused together, misaligned, broadened, split or forked (bifid), and sometimes some of the ribs are missing. Boys have an increased risk of developing inguinal hernia, a condition characterized by protrusion of parts of the large intestine through an opening in the abdominal wall near the groin.
The trunk, which is the part of the body that extends from the neck to the abdomen, may be disproportionately smaller in comparison to their height. In addition, affected individuals may be shorter than would otherwise be expected for their age and gender (Short stature). Affected individuals may have a Short neck with limited mobility. Some individuals have abnormal sideways curvature of the spine, a condition called scoliosis. Scoliosis is usually mild, but, in rare instances, can be severe. Scoliosis usually does not get worse, but should be carefully followed with spine x-rays
Because of the malformation of the spine and ribs, the lungs of affected individuals may not be able to grow and develop properly. This is known as thoracic insufficiency syndrome. Affected infants and children cannot expand their chests sufficiently with causes reduced lung capacity, which means the lungs can hold less air than they normally would. Consequently, they can have difficulties breathing and experience repeated respiratory infections. Breathing problems are usually mild or moderate, but sometimes can become life-threatening and be fatal. Some children may develop High blood pressure of the pulmonary artery, which is the main artery that delivers blood to the lungs (pulmonary hypertension). Pulmonary hypertension is a chronic and, if not treated, life-threatening complication. Reduced lung capacity also increases the risk of Heart failure another life-threatening complication.
Despite the potential for serious complications, most individuals with spondylocostal dysplasia live until adulthood. They may experience chronic back pain. Intelligence is usually unaffected, and neurological complications are rare.
Researchers are studying spondylocostal dysplasia to determine whether there are any genotype-phenotype correlations. Genotype is the distinct set of genes a person carries. Phenotype refers to the observable characteristics of a person. People with an altered LFNG gene usually have the most severe shortening of the spine. People with an altered HES7 gene have improper separation (malsegmentation) of the bones of the entire spine. People with an altered DLL3 gene usually (but not always) have mild scoliosis that does not require surgical intervention.
What are the causes for jarcho levin syndrome?
Spondylocostal dysplasia is caused by a change (mutation) in one of at least five different genes, specifically the DLL3, MESP2, LFNG, HES7, and TBX6 genes. An altered DLL3 gene is the most common cause. Many people do not have a mutation in any of these genes, suggesting that as-yet-unidentified genes also cause spondylocostal dysplasia. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the protein, this can affect many organ systems of the body.
The DLL3, MESP2, LFNG, and HES7 genes are inherited in an autosomal recessive manner. There are reports of the TBX6 gene being inherited in an autosomal dominant as well as in a recessive manner. Most genetic diseases are determined by the status of the two copies of a gene, one received from the father and one from the mother.
Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual inherits one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the altered gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females. In some individuals, an autosomal dominant disorder is due to spontaneous (de novo) genetic mutation that occurs in the egg or sperm cell. In such situations, the disorder is not inherited from the parents.
The altered genes that cause spondylocostal dysplasia produce proteins that are involved in the NOTCH signaling pathway. This pathway is a series of chemical reactions that are vital to the health and function of the body, particularly with the development of the spine and ribs. The protein produced by the altered gene is inefficient or defective, or the gene does not produce enough of the protein. Without the protein in question, the normal chemical reactions that occur in the NOTCH signaling pathway are impaired, leading to the signs and symptoms of spondylocostal dysplasia.
What are the treatments for jarcho levin syndrome?
The treatment of spondylocostal dysplasia is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, specialists who diagnose and treat skeletal disorders (orthopedists), orthopedic surgeons, specialists who diagnose and assess heart disorders (cardiologists), specialists who diagnose and treat lung disorders (pulmonologists), and other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment. Genetic counseling is recommended for affected individuals and their families. Psychosocial support for the entire family is essential as well.
Infants who experience breathing difficulties can require some form of respiratory support. This can include the use of a machine or device to help an infant breath. Some infants may require intensive care, which involves constant monitoring in a hospital. Surgery is used to repair an inguinal hernia. If scoliosis is severe enough, surgery may be required to straighten the spine. Antibiotics may be necessary to treat recurrent respiratory infections.
The vertical expandable prosthetic titanium rib (VEPTR) was approved by the FDA in 2004 as a treatment for thoracic insufficiency syndrome (TIS) in pediatric patients. TIS is a congenital condition where severe deformities of the chest, spine, and ribs prevent normal breathing and lung development. The VEPTR is an implanted, expandable device that helps straighten the spine and separate ribs so that the lungs can grow and fill with enough air to breathe. The length of the device can be adjusted as the patient grows. For treatment of spondylocostal dysplasia, ribs are separated and VEPTRs are placed on the concave side of the chest. It is manufactured by DePuy Synthes Spine Co. in Raynham Mass.
What are the risk factors for jarcho levin syndrome?
Spondylocostal dysplasia is a rare disorder. The exact prevalence or incidence of the disorder is unknown. Because it is a rare disorder, some people may go undiagnosed or misdiagnosed, making it difficult to determine the true frequency in the general population. Spondylocostal dysplasia affects both men and women, and is seen in all ethnic groups (panethnic).
Is there a cure/medications for jarcho levin syndrome?
Jarcho-Levin syndrome is not currently curable. However, there are a few different medications that may help to decrease the symptoms of this disease.
1. Irinotecan: This is the most common drug used for treating jarcho levin syndrome, and it works by inhibiting the growth of cancer cells in the body. It's usually administered intravenously once every two weeks to three months, depending on how quickly your tumor grows and whether you're responding to treatment.
2. Cisplatin: This chemotherapy drug is commonly used to treat people with jarcho levin syndrome that has spread to other parts of their bodies (metastasized), as well as those who suffer from kidney failure due to cancer or another condition. It can be administered intravenously or orally (by mouth) on an ongoing basis until further treatment options are available.
3. Cladribine: This medication is often given to patients who have lung cancer that has spread throughout the body (known as a metastatic disease), along with other types of cancer such as breast cancer and leukemia that have been resistant to other treatments such as chemotherapy or radiation therapy.
4. Levocarnitine: This is a treatment for those with the more advanced forms of JLS. It helps to improve the ability to break down fat and release energy from fats, which can be a particular problem for kids with JLS due to their low muscle tone.
5. Methylcobalamin (or methyl B12): This is a vitamin that helps with nerve function, as well as cell growth and repair. Patients with JLS may have problems absorbing this vitamin from food, so it's often given intravenously or in pill form.
6. Anticonvulsants (such as carbamazepine): These medications are used to prevent seizures by preventing abnormal nerve impulses in the brain. They can help reduce pain and make it easier for patients with JLS to sleep because they reduce excessive muscle tension throughout the body during sleep.
7. Botulinum Toxin Type A (BTX-A): BTX-A is an anti-inflammatory injection that blocks signals from muscles to nerves so that patients with JLS can relax their muscles without feeling pain from overworking them during exercise therapy sessions.
Difficulty breathing, especially during sleep,Swelling of the face, lips, and tongue,Edema (swelling) in the legs and abdomen,extreme fatigue (tiredness)
Congenital heart disease,Intracranial hemorrhage,Respiratory failure, requiring mechanical ventilation and/or tracheostomy placement,Hepatic dysfunction