What are the other Names for this Condition? (Also known as/Synonyms)

• EDS, Kyphoscoliotic Type
• Ehlers-Danlos Syndrome, Oculoscoliotic Type
• Nevo Syndrome

What is Kyphoscoliotic Ehlers-Danlos Syndrome? (Definition/Background Information)

• Kyphoscoliotic Ehlers-Danlos Syndrome is an extremely rare, inherited, connective tissue disorder, characterized by abnormalities in the formation of collagen, an important and the most abundant protein in the body
  • Connective tissue is made up of structural proteins known as collagens and fibroblast cells, which are arranged in rows
  • These tissues connect bone-bone and muscle-bone, and give strength, support, and elasticity to various structures of the body, like skin, joints, and walls of blood vessels
  • There are 3 types of connective tissue, namely, tendons, ligaments and cartilages
• Kyphoscoliotic EDS is caused by mutation(s) in the PLOD1 gene. This gene codes for an enzyme called lysyl hydroxylase 1, which is crucial for cross-linking collagen fibers, to render them strong and pliable. A mutation in PLOD1 therefore weakens the collagen network formation throughout the body, resulting in the disorder
• The characteristic symptom in individuals with Kyphoscoliotic Ehlers-Danlos Syndrome is kyphoscoliosis, the abnormal curving of spine in two planes. The term ‘kyphoscoliosis’ is a combination of kyphosis and scoliosis. The term kyphosis means an abnormal bending of the upper back, such that the individual appears to have a hunched back; scoliosis indicates the sideways curvature of the spine
• Other signs and symptoms include low muscle tone, eye abnormalities, extreme flexibility of joints, susceptibility for joint dislocations, loose skin, and tendency to bruise easily. Progressive bending of the spine, mitral valve regurgitation, premature arthritis, damage to internal organs, and restrictive lung disease are some potential complications of Kyphoscoliotic EDS
• The diagnosis of Kyphoscoliotic Ehlers-Danlos Syndrome is made by conducting a variety of exams including a physical examination, symptom assessment, evaluation of family medical history, collagen typing, imaging tests, urine tests, and molecular genetic testing (to ascertain gene mutations)
• The treatment options focus on symptomatic treatment and the avoidance of serious complications. The treatment may involve medications for pain and blood pressure, physical therapy, and surgery to correct abnormal spine curvature and bone dislocations
• The prognosis of Kyphoscoliotic Ehlers-Danlos Syndrome depends on the severity of symptoms, and overall health of the affected individual. Life expectancy may be reduced owing to complications involving the heart and/or lungs, when scoliosis is severe
• Since Kyphoscoliotic EDS is an inherited condition, there are no guidelines available to prevent its development. However, if there is a family history of this disorder, prospective parents may benefit from gene mutation testing and genetic counseling

Who gets Kyphoscoliotic Ehlers-Danlos Syndrome? (Age and Sex Distribution)

• Kyphoscoliotic Ehlers-Danlos Syndrome is very rare, with only about 60 cases being reported in current scientific literature
• The manifestation of symptoms may begin at birth, or may be observed within the first year of birth
• There is no gender, ethnic, or racial bias in the occurrence of this disorder

What are the Risk Factors for Kyphoscoliotic Ehlers-Danlos Syndrome? (Predisposing Factors)

• Kyphoscoliotic Ehlers-Danlos Syndrome is an inherited disorder, and therefore, having a family history of the disorder is a major risk factor
• Having parents, who are close blood relatives (such as first cousins), is also considered a risk factor

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Kyphoscoliotic Ehlers-Danlos Syndrome? (Etiology)

Kyphoscoliotic Ehlers-Danlos Syndrome is caused by mutation(s) in the PLOD1 gene.

• Under normal circumstances (when the gene is not mutated), it codes for an enzyme called lysyl hydroxylase 1. This enzyme catalyzes the conversion of lysine (an amino acid) to hydroxylysine. Hydroxylysine is crucial for establishing cross-links between collagen fibers and contributes to the strength of connective tissue
• A mutation in PLOD1 gene decreases the levels of functional enzyme, resulting in disorders such as EDS

The mutation is inherited in an autosomal recessive manner. In this type of inheritance, an individual must possess both copies of the causative gene in the defective form in every cell of his/her body for the disease to manifest itself. An affected individual inherits one defective copy of the gene from each parent. The parents are carriers of the disease and are generally not affected.

What are the Signs and Symptoms of Kyphoscoliotic Ehlers-Danlos Syndrome?

The signs and symptoms of Kyphoscoliotic Ehlers-Danlos Syndrome may vary in type and severity, and may include the following:

• Presence of loose, elastic skin; abnormally-thin skin
• A tendency to bruise easily
• Very low muscle tone, which is often present at birth
• Curved spine, which may be present at birth; or, may develop within the first year after birth
• Reduced bone mass (osteopenia)
• Spontaneous rupture of arteries
• Eye abnormalities such as:
  • Small cornea
  • Fragility of membrane covering the eyeball (sclera)
  • Vulnerability to corneal rupture
  • Retinal tear or detachment
• Loose joints (laxity of joints); overly-flexible joints i.e., a range of joint movement beyond what is normally observed
• Joint pain; vulnerability to joint dislocations
• A tendency to develop early-onset osteoarthritis
• Fragile internal organs and other tissues
• Delayed wound healing

How is Kyphoscoliotic Ehlers-Danlos Syndrome Diagnosed?

Kyphoscoliotic Ehlers-Danlos Syndrome is diagnosed on the basis of the following tests and exams:

• A thorough physical examination and an assessment of symptoms
• An evaluation of personal and family medical history
• Measurement of skin hyperextensibilty, by pulling up skin, till resistance is registered
• Beighton scale hypermobility testing for joints: This operates on a 9-point system; a score of over 6 may indicate hypermobility
• Collagen typing using a skin biopsy sample
• Collagen skin mutation testing
• Electron microscopic observation of a skin sample
• Blood tests for checking lysyl hydroxylase or oxidase activity
• Urine test to check for lysyl hydroxylase deficiency
• Imaging tests such as X-ray, computed tomography (CT) scanning, or magnetic resonance imaging (MRI):
  • To visualize bone deformities such as scoliosis and loss of bone mass
  • For structural abnormalities of the heart, along with echocardiography
  • To assess damage to internal organs and tissues
• Genetic testing to confirm mutations in genes that cause EDS

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Kyphoscoliotic Ehlers-Danlos Syndrome?

Kyphoscoliotic Ehlers-Danlos Syndrome may lead to the following complications:

• Progressive curving of the spine
• Early-onset arthritis
• Mitral valve regurgitation, or back flow of blood in to the heart
• Partial or complete joint dislocations
• Restrictive lung disease, because of limited lung expansion and decrease in lung volume
• Retinal detachment; vision impairment

How is Kyphoscoliotic Ehlers-Danlos Syndrome Treated?

The treatment for Kyphoscoliotic Ehlers-Danlos Syndrome is symptomatic, as there is no cure for the condition. Often, a coordinated effort by professionals from various specialties may be needed to help the affected individual achieve a certain quality of life.

The following are some measures for treating the symptoms of Kyphoscoliotic EDS:

• Medications for pain relief: The strength of medication administered depends on the severity of pain
• Medications, to reduce blood pressure (necessitated by fragile blood vessels), such as the following:
  • Beta blockers
  • Angiotensin-converting enzyme inhibitors
  • Calcium channel blockers
  • Diuretic pills
• Proper and balanced nutrition
• Vitamin C supplements may be recommended to aid in collagen synthesis and wound healing
• Physiotherapy to strengthen muscles around weak joints
• Braces to stabilize joints and minimize dislocations
• Surgery
  • For correction of curvature in the spine
  • To repair joints damaged by repeated dislocations, if necessary

How can Kyphoscoliotic Ehlers-Danlos Syndrome be Prevented?

Kyphoscoliotic Ehlers-Danlos Syndrome is a genetic disorder, and currently, there are no methods or guidelines available to prevent its occurrence.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• In individuals, who are diagnosed with EDS, the following may be helpful in reducing injuries, dislocations, and bleeding:
  • Avoiding contact sports and other activities that may cause injury
  • Wearing padding over joints that are vulnerable to dislocation
  • Avoiding unnecessary surgical procedures, since wound healing may be compromised
  • If surgery or dental procedures become necessary, then taking precautions against bleeding before, during, and after the procedure or surgery
  • Proper counseling and medical care for women before and during pregnancy, as well as during and after childbirth 
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Kyphoscoliotic EDS

Regular medical screening at periodic intervals with tests, and physical examinations are crucial and are highly recommended.

What is the Prognosis of Kyphoscoliotic Ehlers-Danlos Syndrome? (Outcomes/Resolutions)

• The prognosis of Kyphoscoliotic Ehlers-Danlos Syndrome is determined by the severity of the symptoms, as well as the overall health of the affected individual
• If complications, such as restrictive lung disease or cardiovascular issues arise, it may lead to a decreased lifespan

Additional and Relevant Useful Information for Kyphoscoliotic Ehlers-Danlos Syndrome:

Please visit our Congenital & Genetic Disorders Health Center for more physician-approved health information:

http://www.dovemed.com/diseases-conditions/congenital-genetic-disorders/