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Achondroplastic dwarfism

Achondroplasia is a type of genetic disorder that is a common cause of dwarfism. People with this condition have short stature, usually reaching a full adult height of around 4'0" (1.2 metres). more...

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Incidence/Prevalence

It occurs at a frequency of about 1 in 20,000 to 1 in 40,000 births.

Clinical features

Clinical features of the disease:

  • dwarfism (nonproportional short stature)
  • shortening of the proximal limbs (termed rhizomelic shortening)
  • short fingers and toes
  • a large head with prominent forehead
  • small midface with a flattened nasal bridge
  • spinal kyphosis (convex curvature) or lordosis (concave curvature)
  • varus (bowleg) or valgus (knock knee) deformities
  • frequently have ear infections (due to Eustachian tube blockages), sleep apnea (which can be central or obstructive), and hydrocephalus

Causes

The disorder is a result of an autosomal dominant mutation in the fibroblast growth factor receptor gene 3 (FGFR3), which causes an abnormality of cartilage formation.

People with achondroplasia have one normal copy of the fibroblast growth factor receptor 3 gene and one mutant copy. Two copies are invariably fatal before or shortly after birth. Only one copy of the gene needs to be present for the disorder to be seen. Thus, a person with achondroplasia has a 50% chance of passing on the gene to their offspring, meaning that 1 in 2 of their children will have achondroplasia. Since two copies are fatal, if two people with achondroplasia have children, there's a 1 in 4 chance of it dying shortly after birth; 2 out of 3 surviving children will have normal achondroplasia. However, in 3 out of 4 cases, people with achondroplasia are born to parents who don't have the condition. This is the result of a new mutation.

New gene mutations are associated with increasing paternal age (over 35 years). Studies have demonstrated that new gene mutations are exclusively inherited from the father and occur during spermatogenesis (as opposed to resulting from a gonadal mosaicism).

For the genetic details: More than 99% of achondroplasia is caused by two different mutations in the fibroblast growth factor receptor 3 (FGFR3). In about 98% of cases, the mutation is a Gly380Arg substitution, resulting from a G to A point mutation at nucleotide 1138 of the FGFR3 gene . About 1% of cases are caused by a G to C point mutation at nucleotide 1138.

There are a couple of other syndromes with a genetic basis similar to achondroplasia, namely hypochondroplasia and thanatophoric dysplasia. Both of these disorders are also caused by a genetic mutation in the FGFR3 gene.

Diagnosis

Achondroplasia can be detected before birth by the use of prenatal ultrasound. A DNA test can be performed before birth to detect homozygosity, where two copies of the mutant gene are inherited, a condition which is lethal and leads to stillbirths.

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Lumbar disc herniation & spinal stenosis: Two common causes of low-back pain & sciatica
From Journal of the American Chiropractic Association, 4/1/99 by Herzog, James

Lumbar disc herniation and spinal stenosis are two very common conditions that chiropractors see every day. Quite often, the symptoms of both are similar. That is, there is usually back pain, with or without radiating leg pain. The lifetime incidence of low-back pain ranges from 50 to 70 percent, whereas the incidence of sciatica ranges from 13 to 40 percent.' The causes of these complaints vary. The differential diagnosis of back and sciatic pain should include disc herniation, primary bone and metastatic disease, visceral disease, vascular disease, infections, stenosis, fractures or trauma, cauda equina syndrome, and mechanical origin. In addition to the pathologies listed above, other benign conditions may mimic the symptoms of a lumbar disc herniation. These are hip disease, trochanteric bursitis, piriformis muscle syndrome, diabetic neuropathy, and meralgia paresthetica. By far, most of what chiropractors see in everyday practice are mechanical disorders and neurologic compressive lesions, such as lumbar disc herniation and spinal stenosis.

Lumbar Disc Disease

The chain of events that usually lead to a lumbar disc herniation is unclear. It is generally thought that a single dramatic event is responsible. This might be a motor vehicle accident, a fall, or some other traumatic episode. Usually, however, the cause of a lumbar disc herniation is a slow and progressive degenerative process.', This process may be minimally symptomatic or even asymptomatic until there is a single dramatic event that causes the symptoms of the herniation to be expressed. Most patients will relate their back and leg pain to a traumatic event; however, if carefully questioned, they will reveal that they have had intermittent episodes of back pain for months or years.

Pain is typically brought on by heavy lifting, repetitive twisting or bending from the waist, or overexertion. The pain will begin in the lower back and spread throughout the buttocks and down one or both legs, typically below the knee. Patients who have suffered a disc herniation may complain of more pain down the leg than in the back. Pain is usually increased with activities and sitting, while it is relieved by bed rest and standing. The radicular pain is usually increased with Valsalva's maneuver-that is, coughing, sneezing, or bearing down during bowel movements.

When performing a physical exam on the patient with low-back pain and sciatica, a comprehensive neurologic examination must be performed. Deeptendon reflexes examination, sensory examination, and motor examination must be performed. A full hip exam should also be performed, as many of these disorders will commonly refer pain down the leg. A vascular examination, which includes pulses of at least the femoral, popliteal, and posterior tibial arteries, should also be performed. An abdominal examination including palpating for any pulsations, possibly indicative of an aortic aneurysm, should also be considered. Typically, if there is a lateral disc herniation in the lumbar spine, root tension signs will be positive. Tension signs/tests are designed to stretch and tighten the sciatic nerve. This leads to compressing an inflamed nerve root against a lumbar disc that is herniated. The standard test is Straight Leg Raising, but there are several variations. Bowstring Sign, Sitting Root test, and Contralateral Straight Leg Raising are but a few. These tests are considered positive only if there is a reproduction of the leg pain.

Frequently, the pattern of radiculopathy is fairly consistent; that is, a unilateral L3/LA disc herniation generally compresses the LA nerve root. Sensory deficits and paresthesia frequently affect the posterolateral thigh, the anterior knee, and lateral leg. There may be muscle weakness in the quadriceps and hip adductors, although these muscles receive their innervation from the L2, L3, and IA levels, so strength may vary. Changes in the patellar reflex are also sometimes seen. A unilateral LA/L5 disc herniation compresses the LS nerve root. This can cause sensory deficits in the anterolateral leg, the dorsum of the foot, and the big toe. Motor weakness may predominantly be seen in the extensor hallucis longus and extensor digitorum longus and brevis. The patient may find it hard to heelwalk. There are no reflex changes with a herniation at this level. A unilateral LS/S1 disc herniation will compress the S1 nerve root. The typical sensory changes are seen in the lateral ankle and foot, the heel, and the web of the fourth and fifth toes. Motor weakness can be seen in the peroneus longus and brevis, the gastroc-soleus complex, and the gluteus maximus. The reflex supplied by the SI nerve root is the Achilles' reflex. Changes found here may be suggestive of a lesion.

When working up a diagnosis for the patient whom you suspect has a disc herniation, two types of tests should be considered. In a young person, an MRI is clearly the test of choice. In an elderly person, a CT scan with a myelogram may prove more useful. Studies have shown that 37 percent of asymptomatic patients over 40 years old who undergo a CT are likely to have a disc herniation confirmed, while the same incidence of asymptomatic patients showing a disc herniation on MRI is only 28 percent.3

Most cases of lumbar disc herniation will respond favorably to conservative treatment and modalities. However, sometimes surgical intervention is required. A condition in which there is an emergent surgical need is where there is either a progressive neurological deficit noted, or if there is a case of cauda equina syndrome. Elective surgical indications are considered in the patient who has persistent sciatica, which is unresponsive to conservative care, or in the patient who has recurrent, incapacitating episodes of sciatica with root tension signs. The patient who has severe debilitating leg pain while at rest, with no positional relief, is likely to have a poor outcome from conservative therapy. Non-operative treatments for the patient with lowback pain and sciatica consist generally of limited bed rest, physical therapy, chiropractic manipulation, and oral antiinflammatory medications, such as NSAIDS. Epidural steroids, while usually beneficial in the short term, seem to provide little long-term improvement with regard to functional status, pain intensity, and rate of surgery to decompress.4 A diagnostic reevaluation should be considered in those patients with chronic symptoms or acute symptoms of greater than four to six weeks without any improvement.

The three phases of lumbar disc degeneration, as described by Kirkaldy-Willis, are: segmental dysfunction phase, unstable phase, and stabilization phase.2 The long-term consequences create a focal kyphosis and then a loss of the posterior tension band of the disc. Over time, this will lead to rotatory instability in the lumbar spine. This instability leads to facet hypertrophy because of the excessive stresses placed on the facets. This will lead to other conditions, such as facet stress fractures and lumbar spinal stenosis.

Lumbar Spinal Stenosis Lumbar spinal stenosis is a narrowing of the vertebral canal and vertebral foramina. This narrowing results in compression of the thecal sac and sometimes the nerve roots directly. The characteristic syndrome that is associated with lumbar stenosis is termed neurogenic intermittent claudication.s This condition should be differentiated from true claudication, which is caused by atherosclerotic changes in the pelvofemoral vessels. The typical age of onset of pain that usually sends a patient to the doctor varies. However, the fifth and sixth decades are the most common. The patient who has lumbar spinal stenosis frequently presents to the physician with the complaint of low-back pain. Patients generally describe a feeling of achiness or stiffness that may radiate into the buttocks. Burning or tightness in the low back and buttocks may be induced by walking, standing, or vigorous activities. Patients will usually complain of low-back stiffness, but with spinal stenosis, the pain is generally aggravated by extension of the spine. Bowel and bladder disturbance or dysfunction is a rare occurrence; however, estimates are that three to four percent of the cases present with urinary dysfunction.' Symptoms considered the hallmark of spinal stenosis are pain that increases with walking or standing, while sitting and leaning forward or lying down alleviate the discomfort.

There are two classifications of spinal stenosis: congenital-developmental stenosis and acquired stenosis. Congenital developmental stenosis can be either idiopathic or achondroplastic. Achondroplastic types are generally seen in cases of dwarfism, cretinism, and Hurler's syndrome. Acquired stenosis includes a wider variety of types. Degenerative joint disease may lead to acquired stenosis, as is common with the elderly. In fact, the most common cause of spinal stenosis is acquired degenerative joint and disc changes. Combined congenital and degenerative forms exist as well. Certainly, post-traumatic episodes of stenosis are commonly seen in our offices. These would include iatrogenically induced cases, as is typically seen in postlaminectomy and postfusion patients. Acquired stenosis may also be seen with certain metabolic disorders, such as Paget's disease and fluorosis. The classification is listed below:

Congenital

Idiopathic

Achondroplastic

Acquired

Degenerative

Central canal

Peripheral canal, lateral recess, nerve root canals

Degenerative spondylolisthesis

Iatrogenic

Postlaminectomy

Postfusion

Postchemonucleolysis

Posttraumatic

Miscellaneous

Paget's disease

Diffuse interstitial skeletal hypertrophy

When deciding which types of radiographic examinations are appropriate for the patient with spinal stenosis, CT scan and MRI examination are both excellent choices. CT scan and MRI examination show the spinal canal, the neural foramina, the joint facets, and the ligaments of the lumbar spine. Both studies will also show whether or not there is any compression on the neural sac or the nerve roots. Other abnormalities and pathologies, such as spinal deformities, osteophyte formation, Paget's disease, facet hypertrophy, and spinal or bony masses, can also be identified with these tests. Xray may be useful in determining the size of the spinal canal. True spinal stenosis is considered to be absolute with a 10-12 mm sagittal diameter.1

Treatments

The treatments for spinal stenosis vary. Certainly, nonoperative treatments should be instituted first. This can include physical therapy; postural muscle strengthening; physical modalities, such as electric muscle stimulation and ultrasound; and medication. Epidural steroid injections, as well as anti-inflammatory medication, may provide relief for leg pain. Chiropractic manipulation, especially in the form of flexion-distraction, usually provides substantial relief for most patients also. The benefits that patients derive with this type of technique are due to an increase in the spinal canal diameter that occurs with flexion of the lumbar spine. Surgery is rarely a medical emergency in the patient who has spinal stenosis. The patient who has intractable pain and those who have failed at conservative modalities usually have very little choice but to undergo surgery. Of course, bowel and bladder dysfunction is considered a medical emergency and requires immediate surgical decompression. In general, the patient with chronic symptoms who has spinal stenosis is usually faced with a decision to either accept a life of decreased function and insidiously progressive neurologic deterioration, or accept the risk-benefit ratio of surgical intervention.

Another helpful tool that should be used in evaluating whether surgery is necessary is if there is any lumbar spine instability noted. To determine this, lateral flexion and extension radiographs are generally used. The rule of thumb is that if there is greater than 4 mm of translation or more than 10 degrees of change in the segmental lordoses, the segment is considered unstable and surgery should be considered. Without surgery, these patients are at higher risk for serious neurologic compromise should a traumatic event occur. Surgery for this condition will generally be either decompression or fusion.

The classification of lumbar spinal stenosis most commonly encountered is either central or lateral recess stenosis. Degenerative changes in the posterior elements usually account for the stenosis. The posterior facets become enlarged and protrude medially and anteriorly. This directly narrows the central canal. The inferior facets are chiefly responsible for central canal narrowing, and the superior facets are chiefly responsible for lateral canal narrowing. With degenerative changes, the posterior annulus bulges posteriorly and small osteophytes add to the canal narrowing. As the disc height is lost, this causes the superior facets to shift up and forward onto the inferior facets and pedicle further, narrowing the foramen. Narrowing of the lateral part of the nerve canal medial to the foramen is responsible for lateral recess stenosis.

Remember that when treating patients with low-back and/or leg pain, it is important to recognize certain signs and symptoms that constitute "red flags." Patients who exhibit night pain, a fever, and unexplained weight loss should trigger warning signs. The history of any malignancy should also warrant further attention. If there is a history of cancer and the x-rays are clear, then further studies, such as bone scans, should be considered.

Lumbar disc herniations and spinal stenosis are two very common conditions. It is important to recognize the differences between them and to reach a proper diagnosis to help ensure the kind of favorable outcome that we all seek.

References

1. Brown DE, Neumunn RD.

Orthopedic Secret 1995. Hanley and Belfi: 185-192.

2. Kirkaldy- WH, Burton CV. Managing Lou, Back Pacn. 3rd ed. Churchill Livingstone, 1992:105-119, 129-141, 20S-210.

3. Weisel, et al, Spine 9:549, 1984

4. Carette S, Leclaire A, Marcoux, et al. Epidural corticosteroid injections for sciatica due to berniated nucleus pulposus. N Engl J Med 1997;336:1634-40

James Herzog, DC, DABCO, is a board certified chiropractic orthopedist, with a private practice in Freehold and Plainsboro, New Jeresey. He is co-founder of chiropractic Orthopedic Associates, a practice and consulting firm, and writes and lectures on orthopedics for the chiropratic and legal professions.

Copyright American Chiropractic Association Apr 1999
Provided by ProQuest Information and Learning Company. All rights Reserved

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