Medical Features

Living with Lowe Syndrome

III. Medical Features, cont'd.

C. Brain and central nervous system
The nervous system includes the brain, spinal cord, and nerves, and it affects the muscles. Lowe syndrome causes problems in most of these areas, including intellectual impairment, seizure disorders, behavior problems, physical changes in the brain, and hypotonia or poor muscle tone.

1. Intellectual impairment. The extent of intellectual impairment in individuals with Lowe syndrome varies widely. Between 10-25% of individuals function intellectually in the low-normal or borderline ranges, and another 25% function in the mild to moderate range of mental retardation. Others function in the severe range. Although it is not possible to predict intellectual outcome at birth, intelligence appears to be stable over the life span of most individuals.

2. Seizure disorders. Seizures occur in about half of all boys with Lowe syndrome. Younger children may have febrile convulsions (seizures caused by fever). These do not usually require medication unless they recur. In older boys, seizures are usually of a major-motor or generalized type. In many cases, these seizure disorders respond well to medication (anticonvulsants or antiepileptic drugs, also known as AEDS). Some individuals develop refractory epilepsy or seizures that are difficult to control. The use of the newly-developed vagus nerve stimulation device, or "pacemaker for the brain," is under evaluation for individuals with Lowe syndrome. This device consists of an implanted generator and a nerve stimulation electrode which transmits antiepileptic electric signals to the brain through the vagus nerve in the neck.

Individuals with seizure disorders may undergo an EEG (electroencephalography) test, which will usually indicate abnormal brain wave patterns and occasionally help to locate the place in the brain where the seizure(s) begin, and may assist in the diagnosis and treatment of the seizures.

3. Behavior problems. Although boys with Lowe syndrome are often happy, loving, and sociable, many also have a characteristic pattern of behaviors that may interfere with everyday functioning. These include temper tantrums, stubbornness, unusual repetitive movements (especially of the hands), inability to concentrate or focus, and unusual obsessions or preoccupations. Some individuals may become violent and self-abusive. These behavioral patterns are thought to be a specific feature of Lowe syndrome. Some studies indicate that for many individuals, the most difficult period for behavior problems is between the ages of 8-13 years. In some cases, however, severe behavior problems continue into adulthood. Behavior modification techniques may be helpful for some. In some cases medication therapy may be effective. Some individuals have experienced improvement with the help of antidepressant and/or antipsychotic medications.

4. Physical changes in the brain. Brain images generated by MRI (magnetic resonance imaging) may demonstrate abnormalities in the brain's white matter. These abnormalities are caused by tiny fluid filled cysts which develop during the first year of life. The exact cause of this condition and its potential effect on brain function is unknown. Brain atrophy, or shrinkage, has also been reported.

5. Hypotonia. Hypotonia, or poor muscle tone, is always present at, or soon after, birth. Hypotonia results in a "floppy" appearance and poor muscle strength. During infancy, hypotonia causes problems with head control and feeding (due to poor sucking). As the boys grow up, motor development is generally delayed in most areas. For instance, learning to walk is usually significantly delayed. About 25% of boys with Lowe syndrome develop the ability to walk alone between the ages of 3-6 years old. By the ages of 6-13, 75% of boys with Lowe syndrome have developed the ability to walk.

Although the hypotonia improves slowly with age, most individuals do not reach normal muscle tone or strength, and related problems can occur as they grow older. Loose or hypermobile joints are also common due to the poor muscle and tendon strength. About half of all affected boys will develop scoliosis, or curvature of the spine, due to weakness in the back muscles. The greatest risk for developing scoliosis occurs during the early teenage through adult years. There is also an increased risk of developing hernias throughout life due to weak muscles in the abdomen. Eating problems may also result from poor muscle tone (see "Eating Difficulties" in Special Health Concerns).

Hypotonia in Lowe syndrome is due primarily to nervous system dysfunction. Individuals have a slight blood elevation of a muscle enzyme called creatinine kinase (CK). Special muscle tests, such as EMGs (electromyography) or muscle biopsies, typically have normal or minimally abnormal results and are not needed to establish a diagnosis of Lowe syndrome. Deep tendon reflexes (such as knee jerk) are usually absent by the first birthday. This may be due to nerve damage, which has occasionally been detected, but may also be due to nervous system dysfunction in the spinal cord. The absence of these reflexes causes no interference with normal function.

The most effective treatment for hypotonia is physical therapy, begun early in infancy if possible.