Hereditary spastic paraplegia hsp, also called familial spastic paraparesis fsp, refers to a group of inherited disorders that are characterized by progressive weakness and spasticity stiffness of the legs. We identified 2 unrelated families, each with 2 siblings with severe methylenetetrahydrofolate reductase mthfr deficiency manifesting a complicated form of. Spastic paraplegia 26 genetic and rare diseases information. More than 50% of affected individuals have some weakness in the legs and impaired vibration sense at the ankles.
Eight novel mutations in spg4 in a large sample of. Truncating mutations in ubap1 cause hereditary spastic. Hereditary spastic paraplegia hsp is a group of hereditary, degenerative, neurological disorders that primarily affect the upper motor neurons. To better address individual patients needs, we investigated a broad range of experienced complaints, activity limitations, and loss of motor capacities in pure hsp. The way we move from simple motions like reaching out to grab something, to playing the piano or dancing is coordinated in our brain. Hereditary spastic paraplegia hsp is a large group of inherited neurologic disorders, in which the prominent feature is a progressive spastic paraparesis. Stopgain mutations in ubap1 cause pure autosomaldominant. Modeling of axonal endoplasmic reticulum network by. Upload file function is needed for users that utilize a 3rd party software. Pdf clinical characteristics of taiwanese patients with. A 14yearold high school student is admitted to the pediatric neurology service because of the.
Importance hereditary spastic paraplegia is a highly heterogeneous group of neurogenetic disorders with pure and complicated clinical phenotypes. The first page of the pdf of this article appears below. Locus and allelic heterogeneity in five families with. Paraplegia in children pdf this is a pdfonly article. Treatment is often focused on reducing spasticity and its physical consequences. Spastic paraplegia type 5 spg5 is a rare subtype of hereditary spastic paraplegia, a highly heterogeneous group of neurodegenerative disorders defined by progressive. Spastic paraplegia is caused by lesions affecting the upper. Hereditary spastic paraplegia support group facebook. The shuffling gait is probably caused by spasticity of the lower limbs, and all. A collection of disease information resources and questions answered by our. The plp1 gene provides instructions for producing proteolipid protein 1 and a modified version isoform of proteolipid protein 1, called dm20.
Hereditary spastic paraplegia hsp or strumpelllorrain syndrome is a heterogeneous group of inherited disorders, with prevalence ranged from 4. Clinical exome sequencing for cerebellar ataxia and. Hereditary spastic paraplegia hsp is a group of neu rodegenerative monogenic disorders characterized by dysfunction of the longer tracts of the spinal cord. Hereditary spastic paraparesis affects both sexes and may begin at any age. Hereditary spastic paraplegia genetic and rare diseases nih. Affected individuals have unsteady spastic gait and hyperreflexia of the lower limbs. Clinical features and management of hereditary spastic. These processes involve many regions and steps, in which nerve cells transport signals along projections known as axons. Oneonone discussions between subjects with hsp is an important way to obtain information, share experiences, and. Patients commonly experience a gradual, yet continuous development of weakness and spasticity or stiffness of the muscles of the legs. Pdf gait patterns in patients with hereditary spastic.
This chapter describes the common neurologic disorders causing spastic paraplegia and the most efficient way to arrive at an etiologic diagnosis. Martinez1, anelyssa dabreu1, iscia lopescendes2, marcondes c. Familial spastic paraplegia motor neuron disease toxic myelopathy. Pdf hereditary spastic paraplegia comprises a wide and heterogeneous group of inherited neurodegenerative and neurodevelopmental. Disease onset ranges from infancy to older adulthood. Hereditary spastic paraplegia with mental impairment, thin corpus callosum and. Proteolipid protein 1 and dm20 are primarily located in the brain and spinal cord central nervous system and are the main proteins found in myelin, the fatty covering that insulates.
If you have problems viewing pdf files, download the. Hereditary spastic paraplegia hsp is a group of inherited diseases whose main. The paraplegia may be accompanied by low grade features of active systemic tb including fever, sweating and weight loss but this is not common. It is usually caused by spinal cord injury or a congenital condition that affects the neural brain elements of the spinal canal. Hereditary spastic paraplegia is a general term for a group of rare inherited disorders that cause weakness and stiffness in the leg muscles. Hereditary spastic paraparesis brain, spinal cord, and. Hereditary spastic paraplegia hsp, also referred to as strumpelllorrain disease, familial spastic paraparesis, and spastic paraplegia, belongs to a group of rare genetic disorders that affect the nervous system. Here we present, for the first time we believe, the neuropathological findings in an hsp type.
Motor neuron degeneration in spastic paraplegia 11 mimics. A collection of disease information resources and questions answered by our genetic and rare diseases information specialists for spastic paraplegia 26. Spastic diplegia definition of spastic diplegia by. The cohort consists of three families with spastic paraplegia type 47 ap4b1 with a common mutation in two families, a family with spastic paraplegia type 50 ap4m1, and two male siblings with x. Hereditary spastic paraparesis hsp is a rare neurodegenerative condition characterized by slowly progressive spastic weakness of the lower limbs and urinary sphincter dysfunction. Pdf hereditary spastic paraparesis hsp or the strumpelllorrain syndrome is the name given to a heterogeneous group of inherited disorders in which. Hereditary spastic paraplegia hsp includes a large and diverse group of genetic disorders whose main feature is progressive spasticity and weakness in the lower limbs, as a result of continuous distal axonopathy caused by defects in the mechanisms that transport proteins and substances along the axons 90, 91. The spg11 phenotype is, in most cases, characterized by a. Experienced complaints, activity limitations and loss of motor. Paraplegia is an impairment in motor or sensory function of the lower extremities. Spastic paraplegia type 5 spg5 is a rare subtype of hereditary spastic paraplegia, a highly heterogeneous group of neurodegenerative disorders defined by. Early in the disease course, there may be mild gait difficulties and stiffness. Neurological examination confirms paraplegia, the clinical signs depending on the level and the extent of the lesion. Hereditary spastic paraplegia hsp, also known as familial spastic.
Filled black squares and circles indicate unambiguously affected individuals, grey squares and circles indicate largely asymptomatic individuals. These disorders are characterized by progressive muscle stiffness spasticity and the development of paralysis of the lower limbs paraplegia. Overlapping molecular pathological themes link charcot. The most common form of autosomal recessive hereditary spastic paraplegia is caused by mutations in the spg11kiaa1840 gene on chromosome 15q.
Hereditary spastic paraplegia type 8 neuropathological. Spg4 is characterized by slowly progressive muscle weakness and spasticity stiff or rigid muscles in the lower half of the body. Mutations in the plp1 gene cause spastic paraplegia 2. Spastic paraplegia type 7 is part of a group of genetic disorders known as hereditary spastic paraplegias. Spastic paraplegia type 7 genetics home reference nih. The spastic paraplegia rating scale a reliable and valid measure of disease severity editors note, oct. Spastic paraplegia1 is usually called masa syndrome, the designation originally suggested by bianchine and lewis 1974, because the main clinical features are summarized by the acronym masa mental retardation, aphasia, shuffling gait, and adducted thumbs. Spasmodic dysphonia in hereditary spastic paraplegia type. Spastic paraplegia30 spg30 is a neurologic disorder characterized by onset of slowly progressive spastic paraplegia in the first or second decades of life. Pmca4 atp2b4 mutation in familial spastic paraplegia. Experienced complaints, activity limitations and loss of. Spastic paraplegia type 2 genetics home reference nih. Stopgain mutations occur in the ubap1 gene in four unrelated autosomal dominant hsp families.
Complex hsp involves additional neurologic symptoms and signs like ataxia, extra pyramidal signs, polyneuropathy, and cognitive decline. Congenital spastic paraplegia definition of congenital. All forms cause degeneration of the nerve pathways that carry signals from the brain down the spinal cord to muscles. This disorder has many forms and can result from many different types of genetic abnormalities. Hereditary spastic paraplegia information page national. Hereditary spastic paraplegia hsp is a group of inherited disorders characterized by progressive spastic paresis of the lower limbs. Hereditary spastic paraplegias are divided into two types. Spastic paraplegia type 7 is an autosomal recessive neurodegenerative disorder mainly characterized by progressive bilateral lower limb spasticity and referred to as a form of hereditary spastic. Axons rely on sophisticated engineering to work properly over long distances and are vulnerable to diseases. In pure hsps, progressive spastic paraplegia is the predominant clinical feature, and it may begin at any age, al. Background spastic gait is a key feature in patients with hereditary spastic paraparesis, but the gait characterization and the relationship. Upper motor neurons in the brain and spinal cord deliver signals to the lower motor neurons, which in turn, carry messages to the muscles. If you have problems viewing pdf files, download the latest version of adobe. Biallelic mutation in the spg11 gene can also cause autosomal recessive juvenileonset amyotrophic lateral sclerosis5 als5.
Rating scale devised for hsp hsp research foundation. Ad the pedigrees of hsp families 1 a, 2 b, 3 c, and 4 d, with ubap1 mutations indicated. Often, subjects and their families feel alone and frustrated with the inability to quickly obtain information. Although with increasing knowledge of the molecular genetics of hsp the distinction is becoming blurred, classically hsps are divided into pure or uncomplicated forms, versus complex or complicated forms. Hereditary spastic paraplegia genes and gene testing hereditary spastic paraplegia genes and gene testing dr elizabeth thompson clinical geneticist sa clinical genetics sa.
The lower thoracic and the lumbar spine are the most common sites affected. The nature of the vast majority of spg11 mutations found to date suggests a lossoffunction mechanism of the encoded protein, spatacsin. Background hereditary spastic paraplegia hsp is a group of genetically heterogeneous disorders characterized by progressive spasticity of the lower limbs. Lathyrism tocp arsenic contrast media used in radiology intra thecal penicillin spinal anesthesia smonsub acute myelo opotic neuropathy long term enteroquinol, large dose. The area of the spinal canal that is affected in paraplegia is either the thoracic, lumbar, or sacral regions. The hsp support group helps people diagnosed with hereditary spastic paraplegia. Hereditary spastic paraplegia hsp leading symptom progressive spastic paraplegia hsp genetic causes with more than 150 known disease genes or loci, hsps are, genetically, very heterogeneous frequency the prevalence of hsps is estimated at up to. Spastic paraplegia article about spastic paraplegia by. Chapter differential diagnosis of acquired causes of. Mutations in the spg4 gene, which encodes spastin protein, are responsible for up to 45% of autosomal dominant cases objective to search for diseasecausing mutations in a large series of italian.
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