SP generally starts with spasticity and weakness in the legs. Onset can occur from infancy into late adulthood. The disease generally progresses slowly to include the urinary bladder and mild impairment of vibratory sense in the legs. It may be classified as "uncomplicated" or "pure" if neurologic impairment is limited to these symptoms or it may be called "complicated" if other neurologic findings, such as seizures, dementia, muscle wasting or peripheral neuropathy are also present. This distinction has become less important as the genetics of HSP is becoming better understood. Generally, progression of SP is slow and it does not reduce the life span.
Clinical examination by a neurologist will reveal signs of upper motor neuron damage, particularly spasticity and increased, brisk or hyperactive reflexes, especially in the lower part of the body. There may be mild involvement of the hands. Electrical studies (EMG, NCV) may be done to rule out other disorders and confirm there is no problem with lower motor neurons. Imaging studies (CT, MRI) may be done to rule out other disorders, such as tumor and spinal disc abnormalities, that could cause similar symptoms.
Generally careful attention will be paid to family history because SP is often an inherited condition. If a family has a know gene mutation, the patient may be tested to confirm its presence.
Most often people with SP have a family history, although there are patients who are the only case within the family. Inherited SP is called hereditary spastic paraparesis or HSP. Sometimes the disorder is called spastic paraplegia because of the weakness it produces in the legs.
Genetic information about the HSPs is mushrooming. There are at least 35 different genes or gene locations associated with different types of HSP. Currently only several can be tested commercially, although this, too, is improving.
HSP may be inherited as an autosomal dominant disorder, meaning one copy of the mutated gene located on one of the numbered chromosomes, is enough to cause the disease. HSP caused by mutations in atlastin, spastin, NIAPA1, KIAAO196, KIF5A, HSPD1, REEP1 and ZFYVE27 are examples. Families with HSP caused by one of these genes generally have multiple affected family members throughout several generations.
HSP may also be inherited as an autosomal recessive condition, meaning two copies of a mutated gene located on a numbered chromosome, one inherited from mom and the other from dad, are required for the disorder to develop. Generally disorders inherited in this manner appear in several children of an unaffected couple. The parent who has one copy of the mutant gene generally does not show symptoms. There are several genes know to cause HSP inherited in this way: paraplegin, KIAA1840, spastizin, spartin and maspardin.
Less frequently, HSP is an X-linked recessive condition. In disorders of this type the mutated gene is located on the X chromosome. In order for males to be males, they one X chromosome and one Y chromosome. If a male inherits the copy of his mother’s X that carries the disease gene at conception then he will develop the condition. For girls to develop the disease they must receive a disease carrying copy of the X gene from both mom and dad at conception: in other words, they have two copies of the disease gene. Females who have only one copy generally do not develop symptoms, or if they do, they are mild. HSP caused by mutations in LICAM and PLP1 are inherited in this way. Symptoms generally appear at birth or in childhood.
Patients being seen in our clinics may discuss genetic testing with their neurologists and our genetic counselor. To make an appointment click here.
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Symptoms are generalized muscle weakness, flaccid neck muscles and sometimes an inability to walk. Brain involvement may cause seizures, deafness, loss of balance, and mental retardation. Onset varies from early infancy to adulthood with variable progression. Inheritance is maternal mitochondrial, autosomal dominant, or autosomal recessive. (Read more about Mitochondrial Myopathy)
Symptoms are variable weakness of shoulders, hips, face, and neck muscles. Onset ranges from early infancy to adulthood with variable progression; carnitine supplementation is often effective. Inheritance is autosomal recessive. ( Read more about Carnitine Deficiency)
Symptoms are the inability to sustain moderate prolonged exercise or fasting due to the chance of causing severe muscle destruction, urine discoloration, and kidney damage. Onset is young adulthood with variable severity. Inheritance is autosomal recessive. (Read more about Carnitine Palmityl Deficiency)
Symptoms are muscle pain and weakness, with muscle damage and urine discoloration possible during intense exercise of brief duration. Onset ranges from childhood to adolescence. Progression is variable, and avoidance of extreme exercise is recommended. Inheritance is X-linked recessive or autosomal recessive. (Read more about Phosphoglycerate Kinase Deficiency)
Symptoms are variable weakness of shoulders, hips, face, and neck muscles. Onset ranges from early infancy to adulthood with variable progression; carnitine supplementation is often effective. Inheritance is autosomal recessive. (Read more about Carnitine Deficiency)
Symptoms are variable weakness of shoulders, hips, face, and neck muscles. Onset ranges from early infancy to adulthood with variable progression; carnitine supplementation is often effective. Inheritance is autosomal recessive. (Read more about Carnitine Deficiency)
Symptoms are weakness and atrophy of the muscles of the hands and lower legs, with foot deformities and some loss of sensation in the feet. Onset occurs in childhood to early adulthood with progression being slow but variable and not affecting life expectancy. Inheritance is autosomal dominant, autosomal recessive, and X-linked recessive. (Read more about CMT)
Symptoms are similar to CMT, however more severe with delayed motor development in childhood, weakness and muscle wasting of the hands and lower legs, and some loss of sensation in the feet. Onset ranges from early childhood with progression being variable. Inheritance is believed to be autosomal dominant (Read more about Dejerine Sottas Disease)
Symptoms are impairment of limb coordination with weakness, muscle wasting, and sometimes diabetes and heart disease. Onset ranges from childhood to adolescence with progression and severity varying. Inheritance is autosomal recessive. (Read more about Freidreich's Ataxia)
Symptoms of generalized muscle weakness and muscle wasting affecting limb and trunk muscles first with enlarged calves. The disease progresses slowly, with an onset about 2-6 years. Survival is rarely beyond late twenties. Inheritance is X-linked recessive. (Read more about DMD)
Symptoms are almost identical to Duchenne muscular dystrophy with regards to the muscle weakness and wasting, but is often much less severe. There can be significant heart involvement. The disease progresses slowly, with an onset in adolescence or adulthood, with survival well into mid to late adulthood. Inheritance is X-linked recessive. (Read more about BMD)
Symptoms are weakness and wasting of the shoulder, upper arms, and shin muscles with possible joint deformities. Cardiac involvement is common. The disease progresses slowly, with an onset in childhood to early teens. Inheritance is X-linked recessive the majority of the time. (Read more about EDMD)
Symptoms are weakness and wasting affecting shoulder and pelvic girdle muscles. Cardiopulmonary complications occur in later stages of the disease. The disease progresses slowly with onset in childhood to middle age. Inheritance is autosomal recessive or X-linked. (Read more about LGMD)
Symptoms are facial muscle weakness and wasting of the shoulders and upper arms. The disease progresses slowly with some periods of rapid deterioration with onset in childhood to early adulthood. The disease may span many decades. Inheritance is autosomal dominant. (Read more about FSHD)
Symptoms are generalized weakness and muscle wasting affecting the face, hands, feet and neck. People experience delayed relaxation of muscles after contraction. Progression is slow with onset in childhood to middle age, however there are some forms of congenital myotonic dystrophy that can be more severe. Inheritance is autosomal dominant. (Read more about DM)
Symptoms occur as weakness of the in the muscles of the eyelid and throat. Progression is slow and swallowing problems are common as the disease progresses; onset is early adulthood to middle age. Inheritance is autosomal dominant. (Read more about OPMD)
Symptoms are weakness and wasting of muscles of the hands, forearms, and lower legs. Onset is between 40 to 60 years. It progresses slowly and is not life threatening. Inheritance is autosomal dominant. (Read more about DD)
Symptoms are generalized muscle weakness with possible joint deformities. Progression is very slow but onsets at birth. Inheritance is autosomal dominant and autosomal recessive. (Read more about CMD)
Symptoms are weakness of the upper arm and upper leg muscles with some muscle wasting. Onset ranges from childhood to adulthood with progression and symptoms improving with treatment of the underlying thyroid condition. (Read more about Hyperthyroid Myopathy)
Symptoms are weakness of farm and leg muscles with stiffness and muscle cramping. Onset ranges from childhood to adulthood with progression and symptoms improving with treatment of the underlying thyroid condition. (Read more about Hypothyroid Myopathy)
Symptoms are weakness of neck and limb muscles; muscle pain; and sometimes associated with malignancy. Onset ranges from childhood to late adulthood with progression and severity varying as well. This disease can respond to drug therapy. (Read more about Polymyositis)
Symptoms are weakness of the neck and limb muscles, muscle pain, and skin rashes affecting the cheeks, eyelids, neck, chest, and limbs. Onset ranges from childhood to late adulthood with progression and severity varying as well. This disease can respond to drug therapy. (Read more about Dermatomyositis)
Symptoms are weakness of arms, legs, hands, especially the thighs, wrists, and fingers. Onset is typically after 50 years with progression being slow. ( Read more about IBM)
Symptoms are generalized weakness and muscle wasting with muscle twitches. Onset is in adulthood and progression is rapid, with the average survival being 3-5 years. ALS is usually sporadic, with some cases having autosomal dominant or autosomal recessive inheritance. (Read more about ALS)
Symptoms are generalized muscle weakness, weak cry, difficulty swallowing and sucking, and respiratory problems. Onset is between birth and 3 months with rapid progression leading to early childhood death. Inheritance is autosomal recessive. (Read more about SMA)
Symptoms are weakness in arms, legs, and upper and lower torso. Onset is between 6-12 months with progression varying according to the extent of respiratory involvement. Inheritance is autosomal recessive. (Read more about SMA)
Symptoms are weakness in leg, hip, shoulder, arm, and sometimes respiratory muscles. Onset is between 13 months and adolescence with slow progression and no effect on lifespan. Inheritance is autosomal recessive. (Read more about SMA)
Symptoms are generalized weakness and muscle wasting with muscle twitching. Onset is over 18 years into adulthood with variable progression and normal life expectancy. Inheritance is autosomal recessive. (Read more about SMA)>
Symptoms are weakness and muscle wasting of the bulbar muscles (throat and mouth) and skeletal muscles. Facial and muscle jumping is common; breast development, infertility and testicular wasting can occur. It usually affects only men. Females are carriers who are usually asymptomatic or have a mild form. Onset is adulthood with progression being slow and variable with normal lifespan. Inheritance is X-linked recessive. (Read more about SBMA)
Symptoms are muscle stiffness and cramps usually occurring after periods of rest; however muscle function returns to normal with activity. Onset ranges from infancy to childhood with the disease causing discomfort but normal life-expectancy. Inheritance is autosomal dominant and autosomal recessive. (Read more about Mytonia Congenita)
Symptoms are poor or difficult relaxation of muscles which may worsen after repeated use or exercise and is often associated with hyperkalemic periodic paralysis. Onset is childhood to early adulthood with the disease causing discomfort but normal life-expectancy. Inheritance is autosomal dominant. (Read more about Paramyotonia Congenita)
Symptoms are delayed motor development with possible hip dislocation at birth. Onset is early infancy to childhood with progression varying such that it may be disabling. Inheritance is autosomal dominant. (Read more about Central Core Disease)
Symptoms are delayed motor development with weakness of arms, legs, trunk, face, and throat muscles. Onset is in early childhood with progression varying and may be life-threatening. Inheritance is autosomal dominant or autosomal recessive. (Read more about Nemaline Myopathy)
Symptoms are drooping of upper eyelids, facial weakness, blackout spells, weakness of the limbs and trunk muscles, and absent reflexes. Onset is infancy with slow progression. Inheritance is X-linked recessive, autosomal recessive, or autosomal dominant. (Read more about Myotubular Myopathy)
Symptoms are episodes of generalized muscle weakness with periods of paralysis affecting arms, legs, and neck. Onset ranges from childhood to adulthood with varying frequency of the attacks. These diseases may respond to drug therapy. Inheritance is autosomal dominant. (Read more about Periodic Paralysis)
Symptoms are weakness and fatigability of the muscles of the eyes, fact, neck, throat, limbs, and/or trunk. Onset ranges from childhood to adulthood with progression varying. This disease can respond to drug therapy or removal of the thymus gland as an effective treatment. ( Read more about MG)
Symptoms include weakness and fatigue of the hip muscles with aching back and thigh muscles common; sometimes associated with lung tumors. Onset is typically during adulthood with progression varying based on the success of drug therapy and treatment of malignancy. (Read more about Lambert-Eaton Syndrome)
Symptoms are generalized weakness and fatigability of voluntary muscles including those that control mobility, eye movement, swallowing, and breathing. Onset is infancy or childhood, however can be later, with progression varying in severity. ( Read more about CMS)
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