Paine syndrome

Definition

Paine syndrome is a rare genetic condition that is present at birth. Characterized by an undersized head and related abnormalities in the brain, the disease results in severe mental and physical retardation, movement disorders, and vision problems. Most infants with Paine syndrome do not survive their first year of life.

Description

The cerebellum, which is Latin for "little brain," is the part of the brain that controls involuntary movements, such as maintaining balance and coordinating muscles during physical activity. When shaking hands, for example, the cerebellum plays a primary role in coordinating the dozens of muscles involved in this seemingly simple task. Paine syndrome, which is named after the American pediatrician who first described the condition in 1960, interferes with the proper growth of the cerebellum and other parts of the brain while the fetus is still in the womb. Though this syndrome is considered a single entity, it actually includes several disorders that emerge together. The result is a variety of debilitating effects.

Children born with Paine syndrome have microcephaly. This neurological disease, which is also associated with conditions other than Paine syndrome, is characterized by an abnormally small head. The head of an infant with microcephaly is smaller than average when compared to other babies of the same age and gender. This decreased skull size is an indication that the brain did not grow properly during fetal development. The form of microcephaly associated with Paine syndrome causes physical and mental retardation. Aside from a small head, infants with Paine syndrome may have undersized bodies. Motor skills, language abilities, and other aspects of normal development are impaired. Babies with Paine syndrome, for example, may require a feeding tube due to difficulties or trouble swallowing. Unlike most infants, they may seem disinterested in the world around them.

Paine syndrome also produces specific problems related to movement. Infants affected by the disease develop spasticity. This nervous system disorder, in which muscles do not relax properly after being stretched, can cause muscle stiffness, pain, or physical deformity. It can also lead to repetitive spasms by a particular muscle or group of muscles (these spasms are known as myoclonic jerks). Aside from spasticity, an infant with Paine syndrome may experience generalized seizures.

Vision can also be affected, resulting in optic atrophy. This eye disorder causes a degeneration of the nerves carrying information from the eyes to the brain. Optic atrophy can lead to blurry vision or other visual disturbances.

The underlying cause of Paine syndrome, which is sometimes referred to as microcephaly-spastic diplegia syndrome, is unknown. The effects of the disease are thought to stem from the limited growth of the cerebellum and other areas of the brain. Autopsies of affected children have revealed underdevelopment of this region, as well as abnormalities in the cerebrum and other brain structures.

Paine syndrome is considered very similar to another genetic, congenital disease known as Seemanova syndrome. Both diseases have a number of symptoms in common, though Seemanova syndrome lacks certain characteristics of the former (such as an underdeveloped cerebellum). Some doctors view both conditions as variations of a more broadly defined disorder called Paine-Seemanova syndrome.

Genetic profile

The gene responsible for Paine syndrome has not been identified, but is believed to lie on the X chromosome. For this reason, the disease is referred to as an X-linked genetic condition. Only males are affected. Females do not usually develop the symptoms of Paine syndrome but they may be carriers of the gene associated with the disease. This is because women have two X chromosomes , while men only possess one. Even if a woman possesses the gene for Paine syndrome on one of her X chromosomes, she still has a second X chromosome that is free of the faulty gene. This second X chromosome is what protects her from developing symptoms of Paine syndrome, though she may be able to transmit the disease to her children.

Demographics

Paine syndrome is a rare, congenital disease that only affects males. Most children born with it do not survive infancy.

Signs and symptoms

The most visible symptom of Paine syndrome is often the size of the head, which is smaller than normal. Affected infants may experience feeding difficulties or swallowing problems. They may not appear to be growing properly or may seem disinterested in their environment. The development of motor skills and speech is delayed.

In simple terms, Paine syndrome causes structural abnormalities in the cerebellum, cerebrum, and other parts of the brain. The skull itself is abnormally small, due to the fact that its size is dictated by brain growth. Damage to the optic nerve may also occur. In addition, Paine syndrome produces elevated amino acid levels in the urine and cerebrospinal fluid.

Diagnosis

The disease is often diagnosed at birth when the size of the head is measured, though a small head circumference may be identified later during a routine exam if it is not detected shortly after delivery. Imaging procedures (such as an x ray, CT scan, or MRI) are used to identify the structural abnormalities of the brain and skull. Analyses of blood and urine are also performed. An electroencephalogram (EEG), a non-invasive test that measures the electrical activity of the brain, may be recommended to help assess developmental problems or detect relevant brain or nervous system abnormalities.

Treatment and management

There is no cure for Paine syndrome. The changes in brain structure associated with the disease cannot be reversed. When possible, treatment focuses on alleviating symptoms. Anticonvulsants, for example, can be used to help control seizures; dextroamphetamine may also be prescribed to ease symptoms. In addition to drugs, orthopedic surgery is sometimes necessary. Family education and genetic counseling for parents is also recommended.

Prognosis

Due to its debilitating effects on the brain and nervous system, Paine syndrome is usually fatal within one year after birth.

Resources

BOOKS

Victor, Maurice, et al. Principles of Neurology. 7th ed. New York: McGraw-Hill, 2001.

PERIODICALS

Lubs, H.A., P. Chiurazzi, J.F. Arena, et al. "XLMR genes: Update 1996." American Journal of Medical Genetics 64 (1996): 147–57.

Opitz, J.M., et al. "International workshop on the fragile X and X-linked mental retardation." American Journal of Medical Genetics 17 (1984): 5–94.

Paine, R.S. "Evaluation of familial biochemically determined mental retardation in children, with special reference to aminoaciduria." New England Journal of Medicine 262 (1960): 658–65.

ORGANIZATIONS

U.S. National Library of Medicine. 8600 Rockville Pike, Bethesda, MD 20894.

WEBSITES

U.S. National Library of Medicine. <http://www.nlm.nih.gov>.

Greg Annussek