Hereditary spastic paraplegia
Definition
Hereditary spastic paraplegia (HSP) is a hereditary degenerative disorder affecting the corticospinal tracts (long never fibers that supply the upper and lower limbs) within the spinal cord. The disease frequently results in progressive spasticity (involuntary movement) of leg muscles with varying degrees of stiffness and weakness of other muscle groups in the thighs, lumbar spinal area, and muscles responsible for up and down feet movements. The extent of degeneration and severity of symptoms varies among the affected people, even those among the same family group. The age of onset for the disease also varies. Some families show a pattern of disease, with symptoms developing earlier in each new generation. In most individuals, however, the disease onset occurs between the second and the fourth decades of life, with a few cases beginning later, or as early as infancy and early childhood.
Description
Other names of this disorder are hereditary spastic paraparesis, Strumpell-Lorrain syndrome, Strumpell disease, familial spastic paraparesis, spastic spinal familial paralysis, and Troyer syndrome. When the only manifested symptom is progressive spasticity, HSP is also known as Pure Hereditary Spastic Paraplegia.
HSP presents three forms of inheritance: autosomal dominant HSP, autosomal recessive HSP, and X-linked HSP. Autosomal dominant HSP requires the presence of an inherited mutation in only one copy of the gene responsible for the disease, whereas autosomal recessive HSP requires mutation in the two copies (maternal and paternal) to manifest the disease. X-linked HSP is rare and the mutated gene is located in the X chromosome, which is transmitted by the mother. HSP is also divided into two categories, uncomplicated HSP and complicated HSP.
Demographics
As usually happens with other rare neurological diseases, the HSP symptoms may overlap or be mistaken with other neurodegenerative disorders. Consequently, HSP incidence is only estimated, with approximately three cases out of 100,000 individuals as an average estimate for the United States and Europe. Ninety percent of HSP cases are uncomplicated and do not affect life expectancy.
Causes and symptoms
Hereditary spastic paraplegia (HSP) belongs to a group of neurodegenerative (progressive nervous system dysfunction) disorders with common symptoms of progressive and usually severe weakness and spasticity of the lower limbs. However, mutations in different genes may result in HSP, a phenomenon known as genetic heterogeneity. For instance, uncomplicated HSP may be inherited as an autosomal dominant mutation in about 70% of cases; but the involved mutated gene may be a different one, located in a different chromosome, from one family to another. Any of these genes is generically known as spastic paraplegia gene or SPG.
SPGs responsible for the uncomplicated form of the disease have been identified in chromosomes 2, 8, 12, 14, 15, 19, and 20; and an autosomal dominant complicated HSP gene has been found in chromosome 10. Autosomal recessive HSP may be caused by other than the abovementioned SPGs, also located either in chromosome 8 or 15, or yet in chromosome 16. One form of autosomal recessive HSP, the Troyer syndrome, is associated with a SPG located in chromosome 13. Two different genes associated with autosomal recessive HSP have also been identified on the X chromosome. Approximately 40–50% of all cases of autosomal dominant HSP are caused by SPG located on chromosome 2.
Uncomplicated autosomal dominant HSP may start at any phase of life, from infancy or early childhood to adulthood or old age. In children, uncomplicated HSP progresses until adolescence and then stabilizes, resulting in partial walking disability. However, complete paralysis of the legs is rare in uncomplicated HSP, whatever the age of onset.
Autosomal recessive HSP is the complicated form of the disease with onset between two and 16 years of age. Complicated HSP symptoms continually progress and may be associated with other neurological conditions, such as epilepsy, mental retardation, peripheral neuropathy (numbness, pain, and sensory changes in nerves of limb extremities), ocular (eye) degenerations, such as retinopathy and/or the destruction of optic nerve tissues (ocular neuropathy). Other clinical complications are ataxia (motor coordination disorders), dysarthria (speech disorders), nystagmus (repetitive and involuntary eye movements), and ichthyosis (abnormal dryness, scaling, and thickening of the skin). However, these neurological symptoms may be caused by other disorders present at the same time. For instance, a person with uncomplicated HSP may have peripheral neuropathy due to diabetes.
Diagnosis
Family clinical history and physical and neurological examinations are the first tools in HSP diagnosis. The physician will conduct comparative examination of muscle tone and strength between arms and legs and look for signs of weakness in specific muscle groups of the thigh, presence of abnormal increase of deep tendon brisk reflexes in the lower extremities, loss of ankle flexibility, and decrease of sensation in the lower extremities. Genetic screening for SPG is the definitive test to avoid misdiagnosis.
Treatment
There is no curable or preventive treatment for HSP, except for antispasmodic drugs to reduce muscle spasms. However, symptomatic treatment for sensitive neuropathy may also be necessary in recessive HSP. Supportive care includes physical therapy and devices to assist with walking.
Resources
BOOKS
Fenichel, Gerald M. Clinical Pediatric Neurology: A Signs and Symptoms Approach, 4th ed. Philadelphia: W. B. Saunders Company, 2001.
ORGANIZATIONS
Genetic Alliance. 4301 Connecticut Avenue, N.W., Suite 404, Washington, DC 20008-2369. (202) 966-5557 or (800) 336-GENE (4363); Fax: (202) 966-8553. info@geneticalliance.org. http://www.geneticalliance.org.
National Ataxia Foundation (NAF). 2600 Fernbrook Lane, Suite 119, Minneapolis, MN 55447-4752. (763) 553-0020; Fax: (763) 553-0167. naf@ataxia.org. http://www.ataxia.org.
Spastic Paraplegia Foundation. P.O. Box 1208, Forston, GA 31808. (978) 256-2673. info@sp-foundation.org. http://www.sp-foundation.org.
Worldwide Education & Awareness for Movement Disorders (WE MOVE). 204 West 84th Street, New York, NY 10024. (212) 875-8312 or (800) 437-MOV2 (6682); Fax: (212) 875-8389. wemove@wemove.org. http://www.wemove.org.
Sandra Galeotti
