Hereditary Sensory Neuropathy Type II (HSNII) is a rare, non-progressive genetic condition that results in the loss of sensations due to malformed nerve cells.
What are the other Names for this Condition? (Also known as/Synonyms)
- Hereditary Sensory and Autonomic Neuropathy Type II (HSAN2)
- Morvan Disease
- Neurogenic Acroosteolysis
What is Hereditary Sensory Neuropathy Type II? (Definition/Background Information)
- Hereditary Sensory Neuropathy Type II (HSNII) is a rare, non-progressive genetic condition that results in the loss of sensations due to malformed nerve cells
- Multiple genetic mutations are known to cause this rare disorder. The causative genes include WNK1, FAM134B, KIF1A, and SCN9
- Individuals with HSNII experience sensory nerve dysfunction signs and symptoms (i.e., sensory neuropathy), which includes a reduced ability to feel hot or cold, and a reduced ability to feel pain leading to delayed wound healing
- Additionally, those with Hereditary Sensory Neuropathy Type II may also have an abnormally-functioning autonomic nervous system, which can lead to difficulty in swallowing, breathing, and digesting
- There is currently no known cure or preventive measures available for Hereditary Sensory Neuropathy Type II, but the symptoms may be managed to alleviate pain and stress. With early diagnosis of wounds and continued management of the condition, individuals with HSNII can have a better quality of life
Who gets Hereditary Sensory Neuropathy Type II? (Age and Sex Distribution)
- Hereditary Sensory Neuropathy Type II is a rare autosomal recessive disorder with an unknown prevalence
- Individuals with HSNII are born with the condition (congenital manifestation). The signs and symptoms may not appear until puberty
- It affects both males and females equally
- The disorder is reported in higher proportions among Eastern Canadians
What are the Risk Factors for Hereditary Sensory Neuropathy Type II? (Predisposing Factors)
- Hereditary Sensory Neuropathy Type II is an inherited disorder, and hence, having a family history of the condition is a major risk factor
It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.
Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.
What are the Causes of Hereditary Sensory Neuropathy Type II? (Etiology)
The cause of Hereditary Sensory Neuropathy Type II is a recessive mutation in either the WNK1 gene on chromosome 12 (A), the FAM134B gene on chromosome 5 (B), the KIF1A gene on chromosome 2 (C), or in the SCN9A gene on chromosome 2 (D).
- WNK1 gene encodes for a protein involved in neuron transmissions in Schwann cells of the nervous system. The mutation that causes HSNIIA creates a shortened form of WNK1 that is theorized to play a role in the disruption of pain response
- FAM134B gene encodes for a protein involved in the structure of the Golgi apparatus of sensory neurons. The mutation that causes HSNIIB triggers a disruption in proper sorting and modification of necessary cellular molecules in cells, causing poor nerve survival
- KIF1A gene encodes for a protein that is involved in transporting vesicles throughout the cell. The mutation that causes HSNIIC triggers a disruption in the transport of molecules along nerves, causing a decline in nerve cell function
- SCN9A gene encodes for a voltage-gated sodium channel in nerve cells. The mutation that causes HSNIID results in the loss of function of nerve conductions
All 4 mutations that cause different forms of HSNII, adversely affect the nervous system, leading to poor sensory responses.
Hereditary Sensory Neuropathy Type II is inherited in an autosomal recessive manner; and so, if the mother and father are both carriers of the mutation, then a child born to them, has a 25% chance of inheriting HSNII.
Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected)
What are the Signs and Symptoms of Hereditary Sensory Neuropathy Type II?
The common signs and symptoms of Hereditary Sensory Neuropathy Type II include:
- Inability to feel pain, touch, or temperature
- Overactive sweat glands (hyperhidrosis)
- Slow pupillary reaction to light
- Weak or absent reflexes
- Numbness in the hands or feet
- Open sores and unintentional self-injury
- Loss of taste
- Trouble breathing, digesting, or swallowing
- Blotching of the skin
- Bone erosions
The signs and symptoms of HSNII typically appear within the first few months of life, but it is also possible that significant symptoms may not appear until puberty.
How is Hereditary Sensory Neuropathy Type II Diagnosed?
The diagnosis of Hereditary Sensory Neuropathy Type II may involve:
- Complete physical examination for the signs and symptoms of HSNII and a screening of the patient’s medical history
- Screening of a family medical history, to see if close blood relatives have HSNII
- Neurological testing (electromyography) to test nerve conductance, to determine the extent of neuropathy
- Skin tests to detect abnormalities in sweat production
- Pain and temperature tests
- Nerve biopsy to determine myelin levels and nerve cell deterioration: A nerve biopsy is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis
- Genetic testing to determine, if any of the 4 genes (WNK1, FAM134B, KIF1A, SCN9A) is mutated
Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.
What are the possible Complications of Hereditary Sensory Neuropathy Type II?
Hereditary Sensory Neuropathy Type II is a non-progressive, but irreversible disorder. The potential complications from HSNII may include:
- Infection of open sores, resulting in limb amputation
- Self-mutilation, resulting in unrecognized damage to the body
- Repeated injury, leading to the formation of Charcot joints (destroyed bone and tissue surrounding joints)
- Sudden breathing difficulty (apnea)
- Acid reflux due to digestion difficulty
How is Hereditary Sensory Neuropathy Type II Treated?
Currently, there is no cure for Hereditary Sensory Neuropathy Type II. A relief from pain, symptoms, and stress, due to the disorder can be sought through the following treatment measures:
- Daily self-inspection of limbs for open sores or injury: Since the individual is higher prone to trauma/injury, daily self-inspection will help detect any injury or open wound faster
- Antiseptic treatment to clean infections of open wounds
- Through regular healthcare checkups, including visiting one’s neurologist, physiotherapist, and surgeon
How can Hereditary Sensory Neuropathy Type II be Prevented?
- Currently, there are no specific methods or guidelines for the prevention of Hereditary Sensory Neuropathy Type II, since it is a genetic condition
- Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
- If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
- Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Hereditary Sensory Neuropathy Type II
Regular medical screening at periodic intervals with tests, scans, and physical examinations are mandatory and highly recommended.
What is the Prognosis of Hereditary Sensory Neuropathy Type II? (Outcomes/Resolutions)
The prognosis of Hereditary Sensory Neuropathy Type II is good with appropriate treatment.
- It is important to note that early diagnosis and treatment of any injury or wound may help avoid severe complications. In such cases, the quality of life is good
- Generally, the life expectancy of the affected individuals is reported to be normal
Additional and Relevant Useful Information for Hereditary Sensory Neuropathy Type II:
Although, currently, there is no cure for Hereditary Sensory Neuropathy Type II, research is actively being undertaken to determine methods to potentially limit the adverse effects of the mutations on the neurons.
What are some Useful Resources for Additional Information?
Center for Peripheral Neuropathy
Department of Neurology, The University of Chicago
5841 South Maryland Avenue, MC2030, Chicago, Illinois 60637
Phone: (773) 702-5659
Genetic and Rare Diseases (GARD) Information Center
PO Box 8126 Gaithersburg, MD 20898-8126
Toll-Free: (888) 205-2311
TTY: (888) 205-3223
International Telephone Access Number: (301) 251-4925
Fax: (301) 251-4911
National Institute of Neurological Disorders and Stroke
P.O. Box 5801 Bethesda, MD 20824
Phone: (301) 496-5751
Toll-Free: (800) 352-9424
TDD: (301) 468-5981
Fax: (301) 402-2186
References and Information Sources used for the Article:
http://ghr.nlm.nih.gov/condition/hereditary-sensory-and-autonomic-neuropathy-type-ii (accessed 04/28/2017)
http://www.omim.org/entry/201300 (accessed 04/28/2017)
http://www.ncbi.nlm.nih.gov/books/NBK49247/ (accessed 04/28/2017)
http://onlinelibrary.wiley.com/doi/10.1111/cge.13037/full (accessed 04/28/2017)
http://jamanetwork.com/journals/jamaneurology/fullarticle/791532 (accessed 04/28/2017)
Helpful Peer-Reviewed Medical Articles:
Jerath, N. U., & Shy, M. E. (2015). Hereditary motor and sensory neuropathies: understanding molecular pathogenesis could lead to future treatment strategies. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1852(4), 667-678.
Axelrod, F. B., & Gold-von Simson, G. (2007). Hereditary sensory and autonomic neuropathies: types II, III, and IV. Orphanet Journal of Rare Diseases, 2, 39. http://doi.org/10.1186/1750-1172-2-39
Rao, A. G. (2016). Painless Ulcers and Fissures of Toes: Hereditary Sensory Neuropathy, Not Leprosy. Indian Journal of Dermatology, 61(1), 121. http://doi.org/10.4103/0019-5154.174132
Murthy, S. C., Udagani, M. M., & Patil, M. N. (2002). Hereditary sensory neuropathy-type-II. Indian Journal of Dermatology, Venereology, and Leprology, 68(6), 375.
Harding, A. E., & Thomas, P. K. (1980). The clinical features of hereditary motor and sensory neuropathy types I and II. Brain, 103(2), 259-280.
Ohta, M., Ellefson, R. D., Lambert, E. H., & Dyck, P. J. (1973). Hereditary sensory neuropathy, type II: clinical, electrophysiologic, histologic, and biochemical studies of a Quebec kinship. Archives of neurology, 29(1), 23-37.
Shekarabi, M., Girard, N., Rivière, J. B., Dion, P., Houle, M., Toulouse, A., ... & Rouleau, G. A. (2008). Mutations in the nervous system–specific HSN2 exon of WNK1 cause hereditary sensory neuropathy type II. The Journal of clinical investigation, 118(7), 2496.
Macefield, V. G., Norcliffe-Kaufmann, L., Löken, L., Axelrod, F. B., & Kaufmann, H. (2014). Disturbances in affective touch in hereditary sensory & autonomic neuropathy type III. International Journal of Psychophysiology, 93(1), 56-61.