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Neuropathy, Hereditary Sensory, Type II

NORD is very grateful to Thomas D. 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 II

Acroosteolysis, Giaccai Type
Acroosteolysis, Neurogenic
Congenital Sensory Neuropathy
Hereditary Sensory and Autonomic Neuropathy, Type II (HSAN Type II)
Hereditary Sensory Radicular Neuropathy, Autosomal Recessive
HSAN II
Morvan Disease
Neuropathy, Progressive Sensory, of Children
Radicular Neuropathy, Sensory, Recessive
Sensory Radicular Neuropathy, Recessive

Disorder Subdivisions

No subdivisions found.

General Discussion

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. Some types of HSN are related to or identical with some forms of Charcot-Marie-Tooth disorder, and others are related to or identical with familial dysautonomia (Riley-Day syndrome). The classification of the HSNs is complicated, and the experts do not always agree on it.

Hereditary sensory neuropathy type II (HSN2) is a rare genetic disorder that usually begins in childhood by affecting the nerves that serve the lower arms and hands and the lower legs and feet (the peripheral nerves). Symptoms start with inflamed fingers or toes especially around the nails. Infection is common and worsens as ulcers (open sores) form on the fingers and on the soles of the feet. The loss of sensation in both hands and feet often leads to neglect of the wounds. This can become serious, even leading to amputation in extreme cases, so it is important to care for any such wounds.

The disorder affects many of the body's systems, is characterized by early onset (infancy or early childhood) and is transmitted genetically as an autosomal recessive trait.

Symptoms

Hereditary sensory neuropathy type II is characterized by inflammation of the fingers or toes especially around the nails, usually accompanied by pus and infection and by open sores (ulcers) of the fingers and on the soles of the feet.

Other symptoms include (a) loss of sensation affecting the skin, and sometimes the muscles, tendons, or joints (kinesthetic sensation); (b) loss of feeling in both the arms and legs causing unsteady movement; (c) painless fractures of the limbs that may occur without the patient's awareness; (d) impaired eyesight due to corneal dysfunction; and periodic excessive sweating (hyperhidrosis) followed by shorter periods of lack of ability to sweat (hypohidrosis). Neurological deficits occur in all of the senses.

Some patients with ulcers of the fingers or toes may develop bone complications such as inflammation (osteomyelitis) or breakdown of bone (osteolysis). Left untreated, this may lead to loss of the affected finger or toe.

Causes

Hereditary sensory neuropathy type II is inherited as an autosomal recessive genetic disorder. The faulty gene has been tracked to a location on the short arm of chromosome 12 (12p13.33).

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 12p13.33" refers to band 13.33 on the short arm (p) of chromosome 12. 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.

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.

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.

Affected Populations

Hereditary sensory neuropathy type II is a rare disorder present at birth that affects males and females in equal numbers. Symptoms usually develop during infancy or childhood.

In 1973 only 33 cases of HSN2 from 6 families were reported in the medical literature. By 2004 the number of families had increased to 15, representing nearly 50 cases.

Related Disorders

Symptoms of the following disorders can be similar to those of Hereditary Sensory Neuropathy Type II. 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 I is a rare genetic disorder characterized by a loss of sensation usually affecting the feet and legs more severely than the hands and forearms, and by perforating ulcers (open sores) on the feet. Pain and temperature sensations are affected more than touch- pressure sensation. (For more information on this disorder, choose "Hereditary Sensory Neuropathy Type I" 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.)

Standard Therapies

Diagnosis
Diagnosis of HSN2 depends on clinical, genetic, physiological and pathological criteria. Electromyogram (EMG) and nerve conduction studies may be abnormal. Biopsy of nerve fibers may be used to confirm the diagnosis.

Treatment
Treatment of HSN2 is symptomatic and supportive. Genetic counseling may be of benefit for patients and their families.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact
www.centerwatch.com

Organizations related to Neuropathy, Hereditary Sensory, Type II

References

TEXTBOOKS
Mandler S, Pearl PL. Hereditary Sensory Neuropathy Type II. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:571.

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.

JOURNAL ARTICLES
Auer-Grumbach M. Hereditary sensory neuropathies. Drugs Today (Barc). 2004;40:385-94.

Lafreniere RG, MacDonald ML, Dube MP, et al. Identification of a novel gene (HSN2) causing hereditary sensory and autonomic neuropathy type II through the study of Canadian Genetic Isolates. Am J Hum Genet. 2004;74:1064-73.

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

Alibhoy AT, Senanayake B, Fernando MA, et al. A case of hereditary sensory and autonomic neuropathy (HSAN) Type II. Ceylon Med J. 2000;45:32-33.

Shimoya K, Ishimoto S, Ohnishi A, et al. [A case of hereditary sensory autonomic neuropathy type II with late onset] Rinsho Shinkeigaku. 1999;39:551-54.

FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Neuropathy, Hereditary sensory and Autonomic, Type II; HSAN2. Entry Number; 201300: Last Edit Date; 5/21/2004.

Toth C. Autonomic Neuropathy. emedicine. Last Updated: August 17, 2004. 27pp.
www.emedicine.com/neuro/topic720.htm

Washington University in St. Louis. Neuromuscular Center. Hereditary Sensory & Autonomic Neuropathies (HSAN) nd. 6pp.
www.neuro.wustl.edu/neuromuscular/time/hsn.htm

Hereditary Sensory and Autonomic Neuropathies. Penn State College of Medicine. Faculty Research Expertise Database (FRED). nd. 2pp.
http://fred.hmc.psu.edu/ds/retrieve/meshdescriptor/D009477

Toscano E. Hereditary sensory and autonomic neuropathy type IV. Orphanet. Creation date: December 2003. 5pp.
http://www.orpha.net/data/patho/GB/uk-HSANIV.pdf

Wilson J. Congenital Insensitivity/Indifference to Pain. contact-a-family. Last updated September 2003. 4pp.
www.cafamily.org.uk/userlogin.php

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Report last updated: 2007/08/17 00:00:00 GMT+0