Morquio Syndrome

Morquio Syndrome is another name for mucopolysaccharidosis IV (MPS IV); it was first described by Luis Morquio in 1919 (4). The frequency of Morquio syndrome is 1 in 640,000 births (7).

 
How Morquio Syndrome Is Inherited

Morquio syndrome follows an autosomal recessive inheritance pattern (9).

 
Causes of Morquio Syndrome

A mutation is the GALNS gene, which encodes for N-acetyl galactosamine-6-sulfatase, causes Morquio, type A (4). Type B is caused by mutations of the GLB1 gene, which encodes for β-galactosidase (4). Both enzymes, however, are responsible for keratan sulfate degradation. In type A, the activity of the sulfatase was found to be less than 1% (6). Due to the enzymes’ ineffectiveness, mucopolysaccharides aggregate within intracellular lysosomes. Mucopolysaccharides are long, unbranched chains of repeating saccharide, or sugar, units. They are important components of the body’s connective tissues and are often times covalently linked to proteins. In Morquio Syndrome, the lysosomal enzymes that are responsible for breaking down mucopolysaccharides are ineffective. As a result, the long sugar molecules begin to collect in the body’s cells and connective tissues. The accumulation ultimately causes cellular damage that manifests as skeletal malformations.

 
Physical Characteristics
Face & Skull
  • Mildly coarse facial features
  • Accentuated lower portion of the face
  • Broad mouth
  • Short anteverted nose
  • Corneas of the eyes become cloudy
  • Widely spaced teeth
  • Hypoplasia of tooth enamel
Trunk, Chest, & Spine:
  • Barrel shaped chest
  • Flaring lower rib cage
  • Prominent sternum
  • Stunted neck and trunk
  • Considerably short spine marked platyspondyly
  • Abnormal posture
Arms & Legs:
  • Severe flexion deformities of the limbs
  • Ligamentous laxity, especially at the wrists and small joints
  • Joint restriction prominent at the larger joints, most notably at the hips
  • Awkward gait
  • Knock-knees
  • Flat feet
  • Prominent buttocks
  • Short and stubby hands
What are the X-ray characteristics?

The major radiographic features of Morquio syndrome include marked platyspondyly in the thoracic and lumbar spine. The shape of the vertebrae change from ovoid, to ovoid with anterior projection, to flat. 

Odontoid hypoplasia with atlanto-axial instability is typical. With progression of the disease, acute thoracolumbar kyphosis is possible; the first indication of spinal cord compression is at the level of C1/C2.The skull is mildly dolichocephalic with underdevelopment of mastoid cells and flat or concave mandibular condyles. A flaring lower rib cage with pectus carinatum is typical of the thorax. 

A premature fusion of the ossification centers of the sternum usually occurs. The long bones are short and curved, with irregular tabulation. Metaphyses are irreguarly wide. Ossification centers tend to develop slowly. Coxa valga is characteristic, along with an abnormal femoral neck and flattening of the femoral head. 

Genu Valgus and a medial spur of tibial metaphysis are often times seen. The bases of the second through fifth metacarpals are conically shaped. The feet have irregular contour with delayed ossification of the tarsal bones. There is central constriction and general shortness of the metacarpals and phalanges.

 
Making the Diagnosis

Morquio Syndrome is typically not recognized at birth. Onset does not occur until the second to fourth year of life. The most frequently recognized symptoms include gait disturbance and growth deficiency.

Diagnostic procedures include flexion-hyperextension radiographs of the cervical spine and/or MRI of the cervical or thoracolumbar spine.

To confirm the diagnosis, two-dimension electrophoresis or thin-layer chromatography of isolated urinary glycosaminoglycans is employed.

Heterozygote detection is possible.

Prenatal recognition can be done using amniotic fluid cells and chorionic villi.

 
Musculoskeletal Problems
Lower Limbs

Pectus carinatum and knock-knee deformity (genu valgus) begin at approximately 3 years of age, and progressively worsen as growth continues. Ligamentous laxity plays a part in the development of knock-knee. In severe cases, the knock-knee may interfere with ambulation. Around age 7 or 8, a patient typically has a lower limb osteotomy to correct the deformity. Typically, the outcome is good, and the results are permanent because growth typically stops around this age. However, due to the habitual atlantoaxial instability, neurological integrity may be compromised, and patients have considerable difficulty in learning to walk again.

Hips

Dislocation of the hips is typically observed, especially as weight-bearing increases. The dislocation, however, is asymptomatic and usually does not impair function. Therefore, most patients abstain from surgical intervention. Yet if patients are considerably physically active, especially as adults, symptomatic osteoarthritis of the hip may develop.

Upper Limbs

Ligamentous laxity is severe, especially of the wrists and ankles. The force able to be delivered by the long flexors of the fingers and thumbs becomes considerably weak. The wrists need to be stabilized, which will help to increase the effectiveness of the muscles and to improve function. Wrist fusions have been attempted, however most attempts have failed.

Spine

Atlanto-axial instability along with myelopathy of the upper cervical spinal cord is a severe problem. Upper motor neurons begin to lose function, there is vague pain in the lower limbs, superficial paresthesias of the feet, vibratory sensation progressively worsens, mobility becomes impaired, and the ability to control the sphincters and to breathe is compromised. If left untreated, most males lose their ability to walk and may possibly die of chronic respiratory failure. The course is typically not as severe in female patients. The rate of progression of cervical myelopathy is variable, however surgical intervention is needed to halt the downward trend. Fusion of the upper cervical spine is frequently recommended. However, care must be taken when administering the anesthesia, due to the risks associated with atlanto-axial instability. Spinal fusion may be supplemented by instrumentation (metal implants) to support the bones until the fusion mass consolidates. In cases of diagnostic doubt, further information can be obtained by means of an MRI scan (with flexion-extension views and CSF flow studies). It allows accurate determination of the degree of spinal cord compression and space available for the cord.

 
Problems Elsewhere in the Body
Respiratory

By late teens and adulthood, the ribs are nearly horizontal and the sagittal diameter of the chest is greater than average. As a result, respiratory expansion becomes considerably impaired. Moreover, frequent upper respiratory tract infections, including otitis media, may occur due to the malformation of the rib cage. The trachea is narrow and may collapse during head flexion. Lung function tests and sleep studies are frequently used to diagnose breathing problems in skeletal dysplasias. Regular review by a pulmonologist is recommended. Prolonged breathing difficulties may warrant a tracheostomy and long-term ventilatory support.

Cardiac

Cardiac complications may occur, including cardiomyopathy, valvular disease, or a late onset of aortic regurgitation. Cardiac anomalies are predominately left sided. Severe cases have resulted in death before the age of 20.

Ear

Hearing loss, inguinal hernia, and hepatomegaly are all problems associated with the ear. Hearing aids and tubes are often times required.

Eye

Corneal opacity is typical once patients reach age 5; glaucoma of the eyes and pigmentary retinal degeneration may occur in older patients. Ophthalmologic examination is needed at frequent intervals.

Skin

Cutaneous abnormalities may also be present, including loose, thickened, tough, and inelastic skin, particularly of the extremities. Generalized telangiectasia of the face and limbs has also been reported.

Teeth

Appropriate dental care is required due to the hypoplasia of tooth enamel. Teeth often brown and discolor easily. The permanent posterior teeth have pointed cusps; there is often times pitting of the bucal surfaces. The teeth are also widely spaced.

Mental Capacity

Intelligence and mentality is typically not impaired in Morquio type A. However, progressive mental deficiency does occur in Morquio Type B.

 
What to Look For

Although the first 18 months are characterized by relatively normal development, beyond this age, Morquio patients tend to decline, especially in proportionate growth and mobility.

Any change in walking ability, endurance, or breathing merits further assessment by a physician to rule out spinal cord compression. Specific neurological symptoms such as tingling or numbness in the arms or legs, weakness, shooting leg or arm pain, or problems controlling bladder/ bowel function should be investigated further.

Considering that eye and teeth problems are especially associated with Morquio Syndrome, ophthalmologic consultation and dental examinations are recommended for early detection and treatment.

Generally all skeletal dysplasias warrant multidisciplinary attention. Regular assessment by an orthopedist, geneticist, pediatrician, dentist, neurologist, and physical therapist will provide the most comprehensive treatment.

 
References
  1. Cole, D.E.C. Fukuda, S. Gordon, B.A. Rip, J.W. LeCouteur, A.N. Rupar, C.A. Tomatsu, S. Ogawa, T. Sukegawa, K. Orii, T. Heteroallelic Missense Mutations of the Galactosamine-6-Sulfate Sulfatase (GALNS) Gene is a Mild Form of Morquio Disease (MPS IVA) American Journal of Medical Genetics. 63: 558-565. 1996.
  2. Giugliani, R. Jackson M. Skinner S.J. Vimal C. M. Fensom A. H. Fahmy A. Sjövall. Beson, P. F. Progressive mental regression in siblings with Morquio disease Type B (mucopolysaccharidosis IV B). Clinical Genetics. 32: 313-325. 1987.
  3. Greaves, M.W. Inman, P. M. Cutaneous Changes in the Morquio Syndrome. Br. J. Derm. 81: 29-36. 1969.
  4. Jones, Kenneth L. Recognizable Patterns of Human Malformation. Philadelphia, PA: Elsevier Saunders. 2006
  5. Kopits, Steven E. Orthropedic Complications of Dwarfism. Clinical Orthopedics and Related Research. 144: 153-179. 1976.
  6. Matalon, R.; Arbogast, B.; Dorfman, A. Morquios syndrome: a deficiency of chondroitin sulfate N-acetylhexosamine sulfate sulfatase. (Abstract) Pediat. Res. 8: 436, 1974.
  7. Nelson, J.; Crowhurst, J.; Carey, B.; Greed, L. Incidence of the mucopolysaccharidoses in western Australia. Am. J. Med. Genet. 123A: 310-313, 2003.
  8. Scott, Charles I. Dwarfism. Clinical Symposium, 1988; 40(1):9-10.
  9. Spranger, Jurgen W. Brill, Paula W. Poznanski, Andrew. Bone Dysplasias: An Atlas of Genetic Disorder of Skeletal Development. Oxford: Oxford University Press. 2002.
  10. Taybi, Hooshang. Lachman, Ralph S. Radiology of Syndromes, Metabolic Disorders, and Skeletal Dysplasias. St. Louis, MO: Mosby-Year Book, Inc. 1996.

Trusted Insights from Nemours' KidsHealth

Relaxation Techniques for Children With Serious Illness

Managing Stress

Nothing about serious illness is easy, but one of the hardest things for parents may be watching their child struggle with pain, stress, and anxiety.

Despite what we may sometimes tell ourselves, stress is not just "in our heads." The stress response — also called the flight-or-fight response — causes a rush of adrenaline and other hormones that trigger physical changes in the body: your heart races, your blood pressure rises, you breathe faster, your digestion slows, and your pupils dilate. Chronic stress takes a toll on the body as well as the mind.

The good news is that using a variety of mind-body relaxation techniques can help short-circuit the flight-or-fight response. Relaxation techniques not only can lessen a child's physical symptoms, they can also help him or her (and you!) regain a sense of control and confidence over a situation, helping everyone find moments of peace amid the chaos and isolation of illness and medical treatment.

Techniques That Can Help

These techniques are designed for parents and kids to practice together. Most can be done in a few minutes wherever you are, whether that's a quiet place or a crowded hospital, without any special tools.

However, it's important to note that these techniques should be used as a complement to conventional medical treatment for anxiety and pain, and not as a replacement — doing so could do a child more harm than good.

If your child is suffering from anxiety or pain, ask your doctor what can be done to help. And always check with your health care team to make sure that your child's symptoms are related to stress and not a different medical problem.

Focused Breathing

Pain and stress can leave a child breathing faster and shallower, or even holding his or her breath — all of which can actually keep the stress response going and heighten the intensity of pain. Paying attention to breathing can help calm the mind.

Try this exercise with your child:

  • Step 1. Sit or lie comfortably and put one hand on your stomach, the other on your chest.
  • Step 2. Close your eyes and try to relax all of your muscles, one by one, from the tips of your toes to the top of your head. Don't forget to relax the muscles in your face, neck, and jaw; you may be storing a lot of tension there.
  • Step 3. Breathe deeply and regularly for several minutes— and try to make your stomach (abdomen) rise and fall, not only your chest. This will help you deepen your breath.
  • Step 4. Pay attention to each breath; try to turn all your thoughts to each inhale … exhale. As you breathe out, imagine the tension leaving your body with the breath.

At first, it may be difficult for you and your child to focus on breathing. Distracting thoughts are normal — but rather than following a thought and letting it consume you, try to let it drift out of your mind, like a balloon.

Relaxation Response Method

This technique asks a person to focus on breathing and quiet the mind to create a sense of calmness and well-being. And by repeating a word, phrase, or prayer during the exercise, the mind is able to stay focused more easily. When practicing this, it's normal for thoughts to pop into the mind. Tell your child to disregard them and just focus on the word or phrase he or she is repeating.

Resembling an Eastern form of meditation, this technique — called the relaxation response — was popularized and put into Western practice in the 1970s by Herbert Benson, MD. To elicit the relaxation response, follow Steps 1-4 above, and then:

  • Step 5. Pick a focus word, phrase, sound, or prayer such as "om," "one," or "peace."
  • Step 6. As you breathe, say the focus word silently to yourself as you exhale.
  • Step 7. Continue for 5 or 10 minutes, ideally building up to 10 to 20 minutes for each session.
  • Step 8. When you're finished, do not stand up immediately. Continue sitting quietly for a bit, letting other thoughts back into your mind. Open your eyes, but stay sitting for another minute before getting up.

When practicing, go at your own pace. Don't feel like you have to achieve a deep level of relaxation right away. Often, feelings of calmness and well-being are felt later on or at times of crisis.

To achieve ongoing results, try to practice the technique with your child once or twice daily, but not within 2 hours after eating, as digestion can interfere with the relaxation response. Some people find that the best time to meditate is first thing in the morning, before breakfast.

Guided Imagery

A growing body of medical research suggests that imagery also can help lessen pain and anxiety, and promote positive feelings. In fact, studies have found that people who practice guided imagery during chemotherapy feel more relaxed and positive about their chemo experience than those who don't use the technique.

Guided imagery (also called "visualization") often works best when a person starts with a few minutes of focused breathing. Here's how it works: With eyes closed, imagine a safe place or a location you once visited that brought a feeling of contentment and joy. Hold on to the image of that place for a while, trying to picture all the sights and sounds:

  • What does the ground beneath you feel like? Is it weather warm or a chilly? Is there a breeze?
  • Are there any animal noises in the distance, or nature sounds (like running water) that you could hear?

Getting as descriptive as possible about this safe place will help you and your child get "into" the moment and feel relaxed.

Some children find this exercise more helpful when they are "guided" by a parent, another live instructor, or with a guided imagery CD or DVD.

As with meditation, distracting thoughts will float into the mind as you practice guided imagery. Acknowledge these thoughts, and then let them drift away while you move your attention back to the images in your mind and sounds you hear.

Music Therapy

Just as pleasant images can calm the mind and soothe the body, so can music. Kids who undergo music therapy — the research-based use of music to lift moods and promote mental and physical well-being — have been found to have lowered heart rates and blood pressure, and improved anxiety.

Many hospitals provide a licensed, trained music therapist who can work individually with kids to develop a customized treatment plan that engages them in:

  • active play that includes listening to music
  • dancing or moving the body to music
  • playing instruments or improvising on them
  • singing along

To participate in music therapy, your child doesn't need to read music or have any special musical talents. And the best part is that you can practice music therapy at home. By choosing music that both you and your child enjoy — and setting aside time to listen, dance, sing, or experiment with an instrument together — you, too, can teach your child the joys of music.

Energy Therapy

Energy therapy is based on the theory of bioelectromagnetics, the belief that the electrical currents in all living organisms produce magnetic energy fields that extend beyond the body. Proponents of this therapy believe that gentle, light touch or above-the-body hand movements can redirect energy to places where it's needed in an effort to bring energy into "balance" or harmony.

While the principles of energy therapy have not been scientifically proven, practitioners say it promotes healing and helps kids feel more relaxed, less anxious, and less bothered by pain.

Many different types of energy therapy are practiced all over the world, including therapeutic touch, healing touch, Reiki and Johrei (from Japan), and Qi gong (from China).

In the United States, some hospitals offer therapeutic or healing touch as a complement to standard treatments for anxiety, pain, or other medical problems.

And some nurses, doctors, or other health care providers are certified in healing touch techniques. They may be able to offer this service to your child, or teach you how to practice healing touch at home.

Massage Therapy

If you like to take a more hands-on approach to soothing and comforting your child, you might prefer massage. The benefits of massage are well known, offering muscle relaxation and increased blood flow and oxygen to body parts to help alleviate stress and ease pain.

But some types of massage are not recommended for certain types of conditions, so check with your doctor first before massaging your child or taking your child to a massage therapist.

The most common forms of massage used in complementary medicine include:

  • Swedish massage. Therapists use their hands to move muscles and joints with long, gliding strokes, tapping movements, friction (made by moving hands quickly) and kneading. Massage oils may be used, so be sure to tell the therapist about any allergies or sensitivities to ingredients that your child may have.
  • Deep-tissue massage. Many of the same techniques are used as in Swedish massage, only therapists apply more pressure to specific areas, concentrating on the deeper layers of muscles and connective tissue.
  • Trigger-point massage. Like deep-tissue massage, this technique massages deeper layers of tissue, focusing on what therapists call trigger points ("knots") within the connective tissue or muscles that are usually painful when pressed.

Many hospitals have massage therapists on hand to offer massages to both patients and their family members, so find out if massage therapy is offered at your hospital.

Learn More

These are just a few of the many methods designed to help patients and families cope with pain and anxiety. Many people find that yoga, stretching, or light, gentle exercise also helps to quiet the mind and sooth the body.

To learn more about relaxation techniques, talk to your child's health care team.

Reviewed by: Larissa Hirsch, MD, and Walle Adams-Gerdts, RN, BA, HTCP/I
Date reviewed: April 2011