Hereditary neuropathy with liability to pressure palsy (HNPP) is a

peripheral neuropathy Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...

, a condition that affects the

nerves A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system. A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...

.update 2014 Pressure on the nerves can cause tingling sensations,

numbness Hypoesthesia or numbness is a common side effect of various medical conditions that manifests as a reduced sense of touch or sensation, or a partial loss of sensitivity to sensory stimuli. In everyday speech this is generally referred to as num ...

, pain, weakness,

muscle atrophy Muscle atrophy is the loss of skeletal muscle mass. It can be caused by immobility, aging, malnutrition, medications, or a wide range of injuries or diseases that impact the musculoskeletal or nervous system. Muscle atrophy leads to muscle weakness ...

and even

paralysis Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 50 ...

of the affected area. In normal individuals, these symptoms disappear quickly, but in sufferers of HNPP even a short period of pressure can cause the symptoms to occur.

Palsies Palsy is a medical term which refers to various types of paralysisDan Agin, ''More Than Genes: What Science Can Tell Us About Toxic Chemicals, Development, and the Risk to Our Children;; (2009), p. 172. or paresis, often accompanied by weakness and ...

can last from minutes or days to weeks or even months. HNPP is caused by a mutation in the gene ''

PMP22 Growth arrest-specific protein 3 (GAS-3), also called peripheral myelin protein 22 (PMP22), is a protein which in humans is encoded by the ''PMP22'' gene. PMP22 is a 22 kDa transmembrane glycoprotein made up of 160 amino acids, and is mainly exp ...

'', which makes peripheral myelin protein 22. This protein has a role in the maintenance of the

myelin Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be ...

sheath that insulates nerves, resulting in insufficient conductivity in the nerves. HNPP is part of the group of

hereditary motor and sensory neuropathy Hereditary motor and sensory neuropathies (HMSN) is a name sometimes given to a group of different neuropathies which are all characterized by their impact upon both afferent and efferent neural communication. HMSN are characterised by atypical ne ...

(HMSN) disorders and is linked to

Charcot–Marie–Tooth disease Charcot–Marie–Tooth disease (CMT) is a hereditary motor and sensory neuropathy of the peripheral nervous system characterized by progressive loss of muscle tissue and touch sensation across various parts of the body. This disease is the mos ...

(CMT).

Signs and symptoms

Symptoms and symptom onset vary; some individuals are diagnosed in childhood, others in adulthood, some report minor problems, whilst others experience severe discomfort and disability. In many cases, symptoms are mild enough to go unnoticed. The time period between episodes is known to vary between individuals. HNPP has not been found to alter the lifespan, although in some cases a decline in quality of life is noticed. Some sufferers (10–15%) report various pains growing in severity with progression of the disease. The nerves most commonly affected are the

peroneal nerve The common fibular nerve (also known as the common peroneal nerve, external popliteal nerve, or lateral popliteal nerve) is a nerve in the lower leg that provides sensation over the posterolateral part of the leg and the knee joint. It divides at ...

at the

fibular The fibula or calf bone is a leg bone on the lateral side of the tibia, to which it is connected above and below. It is the smaller of the two bones and, in proportion to its length, the most slender of all the long bones. Its upper extremity is ...

head (leg and feet), the

ulnar nerve In human anatomy, the ulnar nerve is a nerve that runs near the ulna bone. The ulnar collateral ligament of elbow joint is in relation with the ulnar nerve. The nerve is the largest in the human body unprotected by muscle or bone, so injury is ...

at the elbow (arm) and the

median nerve The median nerve is a nerve in humans and other animals in the upper limb. It is one of the five main nerves originating from the brachial plexus. The median nerve originates from the lateral and medial cords of the brachial plexus, and has contr ...

at the wrist (palm, thumbs and fingers), but any peripheral nerve can be affected. Among the signs/symptoms are the following (different symptoms are caused by different nerves, such as the ''foot drop'' caused by the ''

''):

Causes

The condition is caused by a mutation in one copy of the gene ''

'' (

peripheral myelin protein 22 Growth arrest-specific protein 3 (GAS-3), also called peripheral myelin protein 22 (PMP22), is a protein which in humans is encoded by the ''PMP22'' gene. PMP22 is a 22 kDa transmembrane glycoprotein made up of 160 amino acids, and is mainly e ...

, located at

locus Locus (plural loci) is Latin for "place". It may refer to: Entertainment * Locus (comics), a Marvel Comics mutant villainess, a member of the Mutant Liberation Front * ''Locus'' (magazine), science fiction and fantasy magazine ** ''Locus Award' ...

17p11.2). This makes it

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

. PMP22 is involved in maintaining the

sheath that surrounds nerves to facilitate conductivity. The mutation causes

haploinsufficiency Haploinsufficiency in genetics describes a model of dominant gene action in diploid organisms, in which a single copy of the wild-type allele at a locus in heterozygous combination with a variant allele is insufficient to produce the wild-type ...

, where the activity of the normal gene is insufficient to compensate for the loss of function of the other gene.

Genetics

The peripheral myelin protein 22 gene encodes a 22-kD protein that comprises 2 to 5% of peripheral nervous system myelin. Overlap with

type 1A has been found in ''Gly94fsX222'' (''c.281_282insG''), due to

point mutations A point mutation is a genetic mutation where a single nucleotide base is changed, inserted or deleted from a DNA or RNA sequence of an organism's genome. Point mutations have a variety of effects on the downstream protein product—consequences ...

in ''PMP22'' that occur in a minority of cases of HNPP. The point mutations

missense In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution. Substitution of protein from DNA mutations Missense mu ...

nonsense Nonsense is a communication, via speech, writing, or any other symbolic system, that lacks any coherent meaning. Sometimes in ordinary usage, nonsense is synonymous with absurdity or the ridiculous To be ridiculous is to be something which is ...

and splice-site have each been alluded to in HNPP.

Diagnosis

Measuring

nerve conduction velocity In neuroscience, nerve conduction velocity (CV) is an important aspect of nerve conduction studies. It is the speed at which an electrochemical impulse propagates down a neural pathway. Conduction velocities are affected by a wide array of factors ...

may give an indication of the presence of the disease. Other methods via which to ascertain the diagnosis of HNPP are: * Family history *

Genetic test Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

Proband In medical genetics and other medical fields, a proband, proposito (male proband), or proposita (female proband)Bennett, RL. The Language of the Pedigree. In: ''The Practical Guide to the Genetic Family History''. Wiley-Liss. is a particular subjec ...

:*Multi-

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

panel *

Physical exam In a physical examination, medical examination, or clinical examination, a medical practitioner examines a patient for any possible medical signs or symptoms of a medical condition. It generally consists of a series of questions about the patie ...

(lack of ankle

reflex In biology, a reflex, or reflex action, is an involuntary, unplanned sequence or action and nearly instantaneous response to a stimulus. Reflexes are found with varying levels of complexity in organisms with a nervous system. A reflex occurs ...

)

Treatment

There is no current treatment, however management of HNPP can be done via: *

Physical therapist Physical therapy (PT), also known as physiotherapy, is one of the allied health professions. It is provided by physical therapists who promote, maintain, or restore health through physical examination, diagnosis, management, prognosis, patient ...

Occupational therapist Occupational therapists (OTs) are health care professionals specializing in occupational therapy and occupational science. OTs and occupational therapy assistants (OTAs) use scientific bases and a holistic perspective to promote a person's abilit ...

* Ankle/foot

orthosis Orthotics ( el, Ορθός, translit=ortho, lit=to straighten, to align) is a medical specialty that focuses on the design and application of orthoses, or braces. An is "an externally applied device used to influence the structural and functio ...

* Wrist splint * Avoid repetitive movements

Epidemiology

HNPP is a rare disorder. Partly because it is so rare and partly because many people who have it only experience mild symptoms, it is difficult to tell what percentage of people have it. One range of estimates is from one in 50,000 up to about one in 33,333. Another is from one in 119,049 up to one in 6,250. In a study of newborns in Korea who all got a genetic test for the disorder, around one in 1,698 of the newborns had it.

History

Inherited

peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain ...

disorders were first described by Charcot, Marie and Tooth (1886). De Jong (1947) first described HNPP in a Dutch family. Dyck and Lambert (1968) showed nerve conduction studies, and Chance et al. (1993) detected the chromosome deletion in most of the individuals with the HNPP condition.

References

External links

{{DEFAULTSORT:Hereditary Neuropathy With Liability To Pressure Palsy Neurological disorders