$Unique_ID{BRK04085} $Pretitle{} $Title{Paraplegia, Hereditary Spastic} $Subject{Paraplegia Hereditary Spastic HSP Strumpell's Familial Paraplegia Strumpell-Lorrain Familial Spasmodic Paraplegia Spastic Spinal Familial Paralysis Spastic Congenital Paraplegia Spasmodic Infantile Paraplegia Familial Spastic Paraplegia FSP Familial Spastic Paraperesis from Associated HTLV-1 Infection Werdnig-Hoffman Syndrome Arteriovenous Malformation of the Spine Type III} $Volume{} $Log{} Copyright (C) 1987, 1990 National Organization for Rare Disorders, Inc. 398: Paraplegia, Hereditary Spastic ** IMPORTANT ** It is possible the main title of the article (Hereditary Spastic Paraplegia) is not the name you expected. Please check the SYNONYMS listing on the next page to find alternate names, disorder subdivisions, and related disorders covered by this article. Synonyms HSP Strumpell's Familial Paraplegia Strumpell-Lorrain Familial Spasmodic Paraplegia Spastic Spinal Familial Paralysis Spastic Congenital Paraplegia Spasmodic Infantile Paraplegia Familial Spastic Paraplegia FSP Disorder Subdivision: Familial Spastic Paraperesis from Associated HTLV-1 Infection Information on the following diseases can be found in the Related Disorders section of this report: Werdnig-Hoffman Syndrome Arteriovenous Malformation of the Spine, Type III General Discussion ** REMINDER ** The information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Hereditary Spastic Paraplegia is an inherited neurological disorder characterized by slow progressive degeneration of the corticospinal and other nerve cells in the spinal cord. Abnormal narrowness of the passage inside of the vertebral canal can cause compression of the spinal cord and is one possible cause of this condition. This may cause paralysis. The severity of symptoms depends upon how much the nerves are compressed and damaged. Occasionally associated with other conditions, symptoms are usually first noticed during early childhood although they can begin at any age. Weakness, stiffness and muscle spasms first develop in the legs and may later spread to other parts of the body. Symptoms Initial symptoms of Hereditary Spastic Paraplegia usually include weakness, muscle spasms, and stiffness of the legs. Leg muscles may contract or a heel deformity may occur making walking difficult. Speech disturbances can also appear. Difficulty in swallowing, exaggeration of tendon reflexes and general muscle weakening may develop as this disorder progresses. Symptoms can range from mild to severe depending upon the mode of inheritance (dominant or recessive genes), and the degree to which the nerves are compressed or damaged. Hereditary Spastic Paraplegia can be associated with other conditions such as mental retardation, deafness, premature puberty, congenital deformities of the foot, tremors, dwarfism or delayed speech development. Causes In general, the abnormally narrow vertebral canal in the spinal column of people with Hereditary Spastic Paraplegia causes various degrees of nerve compression which leads to muscle weakness and/or paralysis. The disorder may be inherited through either a dominant recessive transmission. Depending upon which mode of transmission has caused the disorder, several subtypes of HSP have been identified. These subtypes can be differentiated by associated symptoms. Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the normal gene and resulting in appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child. In recessive disorders, the condition does not appear unless a person inherits the same defective gene from each parent. If one receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will show no symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is twenty-five percent. Fifty percent of their children will be carriers, but healthy as described above. Twenty-five percent of their children will receive both normal genes, one from each parent and will be genetically normal.) Hereditary and Familial Spastic Paraplegia is usually an inherited neurologic disorder. However, a study has recently been concluded in a family in Paraguay, that shows a definite transmission of Human HTLV-1 virus (known to cause Leukemia and Lymphoma) through breast milk that results in a condition of Spastic Paraplegia in some of the family members. This cause of the Spastic Paraplegia was shown to have no genetic transmission but to have passed from mother to child through nursing. Similar Spastic Paraparesis types associated with HTLV-1 virus transmission have been recognized in persons in Japan. Affected Population According to a study done in Italy, Hereditary Spastic Paraplegia occurs at a rate of 1.3 cases per 100,000 population. Researchers noted that prevalence may be less frequent in other countries. The disorder seems to occur more frequently in males than females. Symptoms are usually first noticed in childhood, but can begin at any age. Related Disorders Symptoms of the following disorders may be similar to Hereditary Spastic Paraplegia. Werdnig-Hoffmann Disease, also known as Progressive Spinal Muscular Atrophy, is a severe progressive neuromuscular disorder which usually begins in infancy. It is characterized by a generalized atrophy and weakness of the muscles of the trunk and extremities which occur as a result of degenerative changes in the spinal cord. This weakness, referred to as the "amyotonia congenital syndrome" may also be found in other neuromuscular disorders. Tendon reflexes in Werdnig-Hoffmann are usually depressed or absent. The rate of progression can vary. In general, the earlier the onset of this disorder, the faster the progression will be. In very rare cases, symptoms may appear after infancy; in these cases, progression is usually slower than in the infantile form. (For more information on this disorder, choose "Werdnig" as your search term in the Rare Disease Database). Arteriovenous Malformation (AVM) of the Spine (Type III) is characterized by a lesion consisting of tangled or coiled blood vessels in the neck. This type of AVM usually first occurs during childhood and is marked by back pain associated with sensory loss and muscle weakness in the legs. The lesion has multiple feeding vessels with a large malformation that often appears to fill the entire spinal canal. These abnormalities are present at birth even though symptoms may be delayed for many years. AVM seems to occur in males more often than females. (For more information on this disorder, choose AVM as your search term in the Rare Disease Database.) Therapies: Standard Treatment for Hereditary Spastic Paraplegia includes careful supervision of feeding when mouth, larynx and/or esophageal muscles are involved. Physical therapy may help maintain muscle use to avoid fixation of joints and muscle contractures. A foot brace may improve muscle or tendon constrictures in the feet. Numerous drugs are available for treatment of muscle spasms and other symptoms. Communication devices may be useful if a patient loses the ability to talk. Other treatment is symptomatic and supportive. Genetic counseling will be helpful to families of affected individuals. Therapies: Investigational The Food and Drug Administration (FDA) has awarded an orphan drug research grant to John H. Growdon, M.D., Massachusetts General Hospital, Boston, MA, for studies on the experimental drug L-threonine for Hereditary Spastic Paraplegia. Infusion of the drug Baclofen by a surgically implanted pump is being studied by scientists for spasticity. Infusion of the drug directly into the spinal space, rather than given orally, seems to provide patients with better relief of spasticity and improves muscle tone for longer periods of time. Less Baclofen seems to be needed when it is infused rather than given orally. Research on Baclofen for spasticity is supported by an Orphan Drug grant from the FDA. More research is needed to provide evidence of the safety and effectiveness of this type of Baclofen. This disease entry is based upon medical information available through September 1990. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Hereditary Spastic Paraplegia, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 NIH/National Institute of Neurological Disorders & Stroke (NINDS) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5751 (800) 352-9424 International Tremor Foundation 360 W. Superior St. Chicago, IL 60610 (312) 664-2344 For information on genetics and genetic counseling referrals, please contact: March of Dimes Birth Defects Foundation 1274 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References HEREDITARY "PURE" SPASTIC PARAPLEGIA: A CLINICAL AND GENETIC STUDY OF 22 FAMILIES: A.E. Harding; J Neurol Neurosurg Psychiatry (October 1981, issue 44 (10)). Pp. 871-883. FAMILIAL SPASTIC PARAPLEGIA, MENTAL RETARDATION, AND PRECOCIOUS PUBERTY: M.I. Raphaelson, et al.; Arch Neurol (December 1983, issue 40(13)). Pp. 809- 810. THE SPINAL CANAL IN FAMILIAL SPASTIC PARAPLEGIA: D. Vassilopoulos, et al.; Eur Neurol (1981, issue 20(2)). Pp. 110-114. INTRATHECAL BACLOFEN FOR SEVERE SPASTICITY, R.D. Penn, et al.; New Eng J Med (June 8, 1989, issue 320 (23)). Pp. 1517-1521. FAMILIAL SPASTIC PARAPARESIS SYNDROME ASSOCIATION WITH HTLV-1 INFECTION, Solazar-Grueso, Edgar F., et al.; N Eng. J. Med, (September 13, 1990, issue 323, (11)). Pp. 732-737.