HSAN I constitutes a clinically and genetically heterogeneous group of diseases of low prevalence. Detailed epidemiological data are currently not available. The frequency of the disease is still reflected by reports of a handful affected families. Although the impressive clinical features of HSAN I are seen by neurologists, general practitioners, orthopedists, and dermatologists, the condition might still be under-recognized particularly for sporadic cases and patients who do not exhibit the characteristic clinical features.

Hereditary motor and sensory neuropathies are relatively common and are often inherited with other neuromuscular conditions, and these co morbidities cause an accelerated progression of the disease.

Most forms HMSN affects males earlier and more severely than females, but others show no predilection to either sex. HMSN affects all ethnic groups. With the most common forms having no racial prediliections, but other recessively inherited forms tend to impact specific ethnic groups. Onset of HMSN in most common in early childhood, with clinical effects occurring before the age of 10, but some symptoms are lifelong and progress slowly. Therefore, these symptoms do not appear until later in life.

Toxic optic neuropathy refers to the ingestion of a toxin or an adverse drug reaction that results in vision loss from optic nerve damage. Patients may report either a sudden loss of vision in both eyes, in the setting of an acute intoxication, or an insidious asymmetric loss of vision from an adverse drug reaction. The most important aspect of treatment is recognition and drug withdrawal.

Among the many causes of TON, the top 10 toxins include:

- Medications

- Ethambutol, rifampin, isoniazid, streptomycin (tuberculosis treatment)

- Linezolid (taken for bacterial infections, including pneumonia)

- Chloramphenicol (taken for serious infections not helped by other antibiotics)

- Isoretinoin (taken for severe acne that fails to respond to other treatments)

- Ciclosporin (widely used immunosuppressant)

- Acute Toxins

- Methanol (component of some moonshine, and some cleaning products)

- Ethylene glycol (present in anti-freeze and hydraulic brake fluid)

Metabolic disorders may also cause this version of disease. Systemic problems such as diabetes mellitus, kidney failure, and thyroid disease can cause optic neuropathy, which is likely through buildup of toxic substances within the body. In most cases, the cause of the toxic neuropathy impairs the tissue’s vascular supply or metabolism. It remains unknown as to why certain agents are toxic to the optic nerve while others are not and why particularly the papillomacular bundle gets affected.

Familial dysautonomia is seen almost exclusively in Ashkenazi Jews and is inherited in an autosomal recessive fashion. Both parents must be carriers in order for a child to be affected. The carrier frequency in Jewish individuals of Eastern European (Ashkenazi) ancestry is about 1/30, while the carrier frequency in non-Jewish individuals is unknown. If both parents are carriers, there is a one in four, or 25%, chance with each pregnancy for an affected child. Genetic counseling and genetic testing is recommended for families who may be carriers of familial dysautonomia.

Worldwide, there have been approximately 600 diagnoses recorded since discovery of the disease, with approximately 350 of them still living.

Peripheral Myelin Protein 22 gene encodes a 22-kD protein that comprises 2 to 5% of peripheral nervous system myelin, it is located on chromosome locus 17p12

Overlap with Charcot-Marie-Tooth disease type 1A has been found in "Gly94fsX222 (c.281_282insG)", due to point mutations of PMP 22 that occur in a minority of cases of hereditary neuropathy with liability to pressure palsy. The point mutations -missense, nonsense and splice-site have each been alluded to in HNPP.

Hereditary neuropathy with liability to pressure palsy is an autosomal dominant genetic disease (which means one parent must be affected). A mutation in one copy of the gene PMP-22 (Peripheral myelin protein 22, 17p11.2) that makes the peripheral myelin protein causes haploinsufficiency, where the activity of the normal gene is insufficient to compensate for the loss of function of the other gene.

Five different clinical entities have been described under hereditary sensory and autonomic neuropathies – all characterized by progressive loss of function that predominantly affects the peripheral sensory nerves. Their incidence has been estimated to be about 1 in 25,000.

TAA is an old term for a constellation of elements that can lead to a mitochondrial optic neuropathy. The classic patient is a man with a history of heavy alcohol and tobacco consumption. Respectively, this combines nutritional mitochondrial impairment, from vitamin deficiencies (folate and B-12) classically seen in alcoholics, with tobacco-derived products, such as cyanide and ROS. It has been suggested that the additive effect of the cyanide toxicity, ROS, and deficiencies of thiamine, riboflavin, pyridoxine, and b12 result in TAA.

The severity of symptoms vary widely even for the same type of CMT. There have been cases of monozygotic twins with varying levels of disease severity, showing that identical genotypes are associated with different levels of severity (see penetrance). Some patients are able to live a normal life and are almost or entirely asymptomatic. A 2007 review stated that "Life expectancy is not known to be altered in the majority of cases".

Hereditary sensory and autonomic neuropathy (HSAN) or hereditary sensory neuropathy (HSN) is a condition used to describe any of the types of this disease which inhibit sensation.

They are less common than Charcot-Marie-Tooth disease.

The Roussy–Lévy syndrome is not a fatal disease and life expectancy is normal. However, due to progressive muscle wasting patients may need supportive orthopaedic equipment or wheelchair assistance.

If patients with HSAN I receive appropriate treatment and counseling, the prognosis is good. Early treatment of foot infections may avoid serious complications. Nevertheless, the complications are manageable, thus allowing an acceptable quality of life. The disease progresses slowly and does not influence the life expectancy if signs and symptoms are properly treated.

The recurrence of DOOR in siblings and the finding of DOOR syndrome in a few families with consanguinity suggest that the condition is an autosomal recessive genetic condition. Mutations in TBC1D24 have been identified in 9 families.

All hereditary motor and sensory neuropathies are inherited. Chromosomes 17 and 1 seem to be the most common chromosomes with mutations. The disease can be inherited in an autosomal dominant, autosomal recessive or X-linked manner.

The severity and prognosis vary with the type of mutation involved.

dHMN V has a pattern of autosomal dominance, meaning that only one copy of the gene is needed for the development of the disease. However, there is incomplete penetrance of this disorder, meaning that some individuals with the disease-causing mutations will not display any symptoms. Mutations on chromosome 7 have been linked to this disease. It is allelic (i.e., caused by mutations on the same gene) with Charcot–Marie–Tooth disease and with Silver’s Syndrome, a disorder also characterized by small muscle atrophy in the hands.

Another rare form of dHMN V is associated with a splicing mutation in REEP-1, a gene often associated with hereditary spastic neuroplegia.

CMT is a result of genetic mutations in a number of genes. Based on the affected gene, CMT can be categorized into types and subtypes.

Distal hereditary motor neuropathy type V (dHMN V) is a particular type of neuropathic disorder. In general, distal hereditary motor neuropathies affect the axons of distal motor neurons and are characterized by progressive weakness and atrophy of muscles of the extremities. It is common for them to be called "spinal forms of Charcot-Marie-Tooth disease (CMT)", because the diseases are closely related in symptoms and genetic cause. The diagnostic difference in these diseases is the presence of sensory loss in the extremities. There are seven classifications of dHMNs, each defined by patterns of inheritance, age of onset, severity, and muscle groups involved. Type V (sometimes notated as Type 5) is a disorder characterized by autosomal dominance, weakness of the upper limbs that is progressive and symmetrical, and atrophy of the small muscles of the hands.

There is currently no cure for FD and death occurs in 50% of the affected individuals by age 30. There are only two treatment centers, one at New York University Hospital and one at the Sheba Medical Center in Israel. One is being planned for the San Francisco area.

The survival rate and quality of life have increased since the mid-1980s mostly due to a greater understanding of the most dangerous symptoms. At present, FD patients can be expected to function independently if treatment is begun early and major disabilities avoided.

A major issue has been aspiration pneumonia, where food or regurgitated stomach content would be aspirated into the lungs causing infections. Fundoplications (by preventing regurgitation) and gastrostomy tubes (to provide nonoral nutrition) have reduced the frequency of hospitalization.

Other issues which can be treated include FD crises, scoliosis, and various eye conditions due to limited or no tears.

An FD crisis is the body's loss of control of various autonomic nervous system functions including blood pressure, heart rate, and body temperature. Both short-term and chronic periodic high or low blood pressure have consequences and medication is used to stabilize blood pressure.

Dejerine–Sottas neuropathy is caused by a genetic defect either in the proteins found in axons or the proteins found in myelin. Specifically, it has been associated with mutations in "MPZ", "PMP22", "PRX", and "EGR2" genes. The disorder is inherited in an autosomal dominant or autosomal recessive manner.

Dejerine–Sottas disease, also known as Dejerine–Sottas syndrome, Dejerine–Sottas neuropathy, progressive hypertrophic interstitial polyneuropathy of childhood and onion bulb neuropathy (and, "hereditary motor and sensory polyneuropathy type III" and "Charcot–Marie–Tooth disease type 3"), is a hereditary neurological disorder characterised by damage to the peripheral nerves and resulting progressive muscle wasting. The condition is caused by mutations in a various genes and currently has no known cure.

The disorder is named for Joseph Jules Dejerine and Jules Sottas, French neurologists who first described it.

Hereditary motor and sensory neuropathy with proximal dominance (HMSN-P) is an autosomal dominant neurodegenerative disorder that is defined by extensive involuntary and spontaneous muscle contractions, asthenia, and atrophy with distal sensory involvement following. The disease starts presenting typically in the 40s and is succeeded by a slow and continuous onslaught. Muscle spasms and muscle contractions large in number are noted, especially in the earliest stages. The presentation of HMSN-P is quite similar to amyotrophic lateral sclerosis and has common neuropathological findings. Sensory loss happens as the disease progresses, but the amount of sensation lost varies from case to case. There have been other symptoms of HMSN-P reported such as urinary disturbances and a dry cough.

Two large families in Japan have been identified with the disease locus to chromosome 3q. From descendants of Japan, HMSN-P was brought to Brazil, from there it is a pretty isolated disease. Through clinical studies, researchers identified that TFG mutations on chromosome 3q13.2 causes HMSN-P. "The presence of TFG/ubiquitin- and/or TDP-43-immunopositive cytoplasmic inclusions in motor neurons and cytosolic aggregation composed of TDP-43 in cultured cells expressing mutant TFG indicate a novel pathway of motor neuron death"

CIPA is caused by a genetic mutation which prevents the formation of nerve cells which are responsible for transmitting signals of pain, heat, and cold to the brain. The disorder is autosomal recessive. It does not appear to have any particular ethnic distribution, though it is more prevalent in cultures in which intermarriage is an accepted practice. Overheating kills more than half of all children with CIPA before age 3.

The genetic mutation is in the gene encoding the neurotrophic tyrosine kinase receptor (SCN9A gene). NTRK1 is a receptor for nerve growth factor (NGF). This protein induces outgrowth of axons and dendrites and promotes the survival of embryonic sensory and sympathetic neurons. The mutation in NTRK1 does not allow NGF to bind properly, causing defects in the development and function of nociceptive reception.

Roussy–Lévy syndrome, also known as Roussy–Lévy hereditary areflexic dystasia, is a rare genetic disorder of humans that results in progressive muscle wasting. It is caused by mutations in the genes that code for proteins necessary for the functioning of the myelin sheath of the neurons, affecting the conductance of nerve signals and resulting in loss of muscles' ability to move.

The condition affects people from infants through adults and is inherited in an autosomal dominant manner. Currently, no cure is known for the disorder.

HSP is a group of genetic disorders. It follows general inheritance rules and can be inherited in an autosomal dominant, autosomal recessive or X-linked recessive manner. The mode of inheritance involved has a direct impact on the chances of inheriting the disorder. Over 70 genotypes had been described, and over 50 genetic loci have been linked to this condition. Ten genes have been identified with autosomal dominant inheritance. One of these SPG4 accounts for ~50% of all genetically solved cases cases, or approximately 25% of all HSP cases. Twelve genes are known to be inherited in an autosomal recessive fashion. Collectively this latter group account for ~1/3 cases.

Most altered genes have known function, but for some the function haven’t been identified yet. All of them are listed in the gene list below, including their mode of inheritance. Some examples are spastin (SPG4) and paraplegin (SPG7) are both AAA ATPases.