Neuropathy, Hereditary Sensory, Type I
NORD is very grateful to Thomas Bird, MD, Professor of Neurology and Head of the Division of Neurogenetics, University of Washington, and Research Neurologist, Seattle VA Medical Center, for assistance in the preparation of this report.
Synonyms of Neuropathy, Hereditary Sensory, Type I
- Neuropathy, Hereditary Sensory and Autonomic, Type I HSAN1
- Neuropathy, Hereditary Sensory Radicular, Autosomal Dominant
- No subdivisions found.
The hereditary sensory neuropathies (HSN) include 4-6 similar but distinct inherited, degenerative disorders of the nervous system (neurodegenerative) that frequently progress to loss of feeling, especially in the hands and feet. The classification of the hereditary sensory neuropathies is complicated, and the experts do not always agree. This report deals with HSN type I. There is a separate report in NORD's Rare Disease Database dealing with HSN type II. One other type of hereditary sensory neuropathy, HSN-III, is related to, or identical with, familial dysautonomia (Riley-Day syndrome). Another type, HSN-IV, is related to, or identical with, a form of Charcot-Marie-Tooth disorder.
Hereditary sensory neuropathy Type I (HSN1) is a rare genetic disorder characterized by the loss of sensation (sensory loss), especially in the feet and legs and, less severely, in the hands and forearms. The sensory loss is due to abnormal functioning of the sensory nerves that control responses to pain and temperature and may also affect the autonomic nervous system that controls other involuntary or automatic body processes.
The disorder is inherited as an autosomal dominant trait, and the mutated gene has been identified and tracked to a site on chromosome 9.
HSNs of various types may attack a single nerve (mononeuropathy) or many nerves simultaneously (polyneuropathy). The resulting symptoms may involve sensory, motor, reflex, or blood vessel (vasomotor) functions.
Major symptoms of HSN1 include loss of sensation, usually affecting the feet and legs more severely than the hands and forearms. Pain and temperature sensations are affected more than touch-pressure sensation. Some patients experience piercing or stabbing sensations (lancinating pains). As the disorder progresses, the feet may develop perforating ulcers (open sores), especially if patients take poor care of them. Reflexes in the legs are decreased or absent. Deafness occasionally occurs.
The degeneration of the soft tissue around the open sores of the feet is a target of infection that may lead to degeneration of the bones of the feet as well. In such cases, amputation of toes and/or the foot may be necessary.
Hereditary sensory neuropathy type I is inherited as an autosomal dominant trait. It results from the mutation of a gene on chromosome 9 (9q22/1-22/3) that is involved in the production of an enzyme known as serine palmitoyltransferase (SPT).
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 9q22.1-22.3" refers to a region on the long arm of chromosome 9 between bands 22.1 and 22.3. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
HSN1 is a rare disorder present at birth, affecting males and females in equal numbers. Symptoms usually develop during the teen years in contrast to the other HSNs, which appear early in the life of the child.
Symptoms of the following disorders can be similar to those of Hereditary Sensory Neuropathy Type I. Comparisons may be useful for a differential diagnosis:
Charcot-Marie-Tooth Disease is a rare hereditary neurological disorder characterized by muscle atrophy and weakness most prominent in the legs and the small muscles of the hands. A decrease in vibration, pain, and thermal sensation in the hand, foot, and lower part of the leg may occur. Stretch reflexes are usually absent. (For more information on this disorder, choose "Charcot-Marie-Tooth Disease" as your search term in the Rare Disease Database.)
Hereditary Sensory Neuropathy Type II is a rare genetic disorder characterized by inflammation of the fingers or toes especially around the nails, usually accompanied by pus and infection (paronychia, whitlows) and by ulcers (open sores) of the fingers and on the soles of the feet. Other symptoms are loss of sensation affecting the skin, and sometimes the muscles, tendons, or joints (kinesthetic sensation). Loss of sensation is noticeable in both arms and legs, rather than primarily in the legs as in Hereditary Sensory Neuropathy Type I. (For more information on this disorder, choose "Hereditary Sensory Neuropathy Type II" as your search term in the Rare Disease Database.)
The symptoms of Peripheral Neuropathy are produced by disease of a single nerve (mononeuropathy, mononeuritis), several nerves in asymmetric areas of the body (mononeuritis multiplex), or many nerves simultaneously (polyneuropathy, polyneuritis, multiple peripheral neuritis). These symptoms may involve sensory, motor, reflex, or blood vessel (vasomotor) function. (For more information on these disorders, choose "neuropathy" as your search term in the Rare Disease Database.)
Syringomyelia is a rare neurological disorder characterized by a fluid- filled cavity (syrinx) within the spinal cord. Patients with Syringomyelia in the upper (cervical and thoracic) part of the spinal cord may first notice loss of feeling for pain and temperature in their fingers, hands, arms, and upper chest. In the early stages, a sense of touch is still present. A loss of feeling may spread over the shoulders and back. Chronic progressive degeneration of the stress-bearing part of a bone joint (Charcot joint) is another symptom. Reflexes in the upper extremities may be absent. When the lumbar and sacral segments of the spine are affected, spasticity, muscle weakness, and muscular incoordination in the lower extremities as well as paralysis of the bladder usually occur. Morvan disease is a severe form of Syringomyelia accompanied by ulceration of fingers and toes. (For more information on this disorder, choose "Syringomyelia" as your search term in the Rare Disease Database.)
Roussy-Levy Syndrome is a rare genetic motor sensory disorder. Major symptoms may include a foot deformity (claw foot), muscle weakness, atrophy of the leg muscles and tremor in the hands. (For more information on this disorder, choose "Roussy-Levy" as your search term in the Rare Disease Database.)
Diagnosis of HSN1 depends on clinical, genetic, physiological and pathological criteria. Electromyograms (EG) and nerve conduction studies may be abnormal. Biopsy of nerve fibers may be used to confirm the diagnosis.
Treatment of HSN1 is symptomatic and supportive. Genetic counseling may be of benefit for patients and their families.
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Organizations related to Neuropathy, Hereditary Sensory, Type I
Mandler S, Pearl PL. Hereditary Sensory Neuropathy Type II. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:570.
Rowland LP. Ed. Merritt's Neurology. 10th ed. Lippincott Williams & Wilkins. Philadelphia, PA. 2000:611.
Menkes JH, Pine Jr JW, et al. Eds. Textbook of Child Neurology. 5th ed. Williams & Wilkins. Baltimore, MD; 1995:182-83.
Auer-Grumbach M. Hereditary sensory neuropathies. Drugs Today (Barc). 2004;40:385-94.
Axelrod FB, Hilz MJ. Inherited autonomic neuropathies. Semin Neurol. 2003;23:381-90.
Auer-Grumbach M, De Jonghe P, Verhoeven K, et al. Autosomal dominant inherited neuropathies with prominent sensory loss and mutilations. Arch Neurol. 2003;60:329-34.
Hilz MJ. Assessment and evaluation of hereditary sensory and autonomic neuropathies with autonomic and neurophysiological examinations. Clin Auton Res. 2002;12 Suppl 1:I33-43
Nicholson GA, Dawkins JL, Blair IP, et al. Hereditary sensory neuropathy type I: haplotype analysis shows founders in southern England and Europe. Am J Hum Genet. 2001;69:655-59.
Verhoeven K, Coen K, De Vriendt E, et al. SPCTLC1 mutation in twin sisters with hereditary sensory neuropathy type I. Neurology. 2004;62:1001-02.
Bejaoui K, Uchida Y, Yasuda S, et al. Hereditary sensory neuropathy type I mutations confer dominant negative effects on serine palmitoyltransferase, critical for sphingolipid synthesis. J Clin Invest. 2002;110:1301-08.
Karkashan EM, Joharji HS, Al-Harbi NN. Congenital insensitivity to pain in four related Saudi families. Pediatr Dermatol. 2002;19:333-35.
Dawkins JL, Hulme DJ, Brahmbhatt SB, et al. Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I. Nat Genet. 2001;27:309-12.
Bejaoui K, Wu C, Scheffler MD, et al. SPTLC1 is mutated in hereditary sensory neuropathy, type I. Nat Genet. 2001;27:261-62.
Nicholson GA, Dawkins JL, Blair IP, et al. The gene for hereditary sensory neuropathy type I (HSN) maps to chromosome 9q22.1-q22.3. Nat Genet. 1996;13;10-04.
FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Neuropathy, Hereditary Sensory and Autonomic, Type I; HSAN1. Entry Number; 162400: Last Edit Date; 9/8/2004.
Nicholson GA. Hereditary Sensory Neuropathy Type I. Last Update: 28 September 2004. 12pp.
Toth C. Autonomic Meuropathy. emedicine. Last Updated: August 17, 2004. 27pp.
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