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.

Genetic counseling is an important tool for preventing new cases if this is wished by at-risk family members. Appropriate genetic counseling is based on an accurate diagnosis. Therefore, clinicians and genetic counselors should use ulcero-mutilating complications as the main diagnostic criteria. Since the disease is inherited as an autosomal dominant trait, there is a Mendelian risk of 50% for subsequent generations regardless of their sex. Prenatal testing for pregnancies at increased risk is possible if the disease-causing mutation has been identified in the family. Predictive testing is useful for young people to avoid serious complications of the 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.

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.

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".

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.

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.

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.

Hereditary sensory neuropathy type 1 is a condition characterized by nerve abnormalities in the legs and feet (peripheral neuropathy). Many people with this condition have tingling, weakness, and a reduced ability to feel pain and sense hot and cold. Some affected individuals do not lose sensation, but instead feel shooting pains in their legs and feet. As the disorder progresses, the sensory abnormalities can affect the hands, arms, shoulders, and abdomen. Affected individuals may also experience muscle wasting and weakness as they get older, but this varies widely within families.

Affected individuals typically get open sores (ulcers) on their feet or hands or infections of the soft tissue of the fingertips (whitlows) that are slow to heal. Because affected individuals cannot feel the pain of these sores, they may not seek treatment right away. Without treatment, the ulcers can become infected and may require amputation of the surrounding area.

Albeit rarely, people with hereditary sensory neuropathy type 1 may develop hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss).

The signs and symptoms of hereditary sensory neuropathy type 1 typically appear during a person's teens or twenties. While the features of this disorder tend to worsen over time, affected individuals have a normal life expectancy if signs and symptoms are properly treated.

Type 1 is the most common form among the 5 types of HSAN. Its historical names include "mal perforant du pied", ulcero-mutilating neuropathy, hereditary perforating ulcers, familial trophoneurosis, familial syringomyelia, hereditary sensory radicular neuropathy, among others. This type includes a popular disease Charcot-Marie-Tooth type 2B syndrome (HMSN 2B). that is also named as HSAN sub-type 1C.

Type 1 is inherited as an autosomal dominant trait. The disease usually starts during early adolescence or adulthood. The disease is characterized by the loss of pain sensation mainly in the distal parts of the lower limbs; that is, in the parts of the legs farther away from the center of the body. Since the affected individuals cannot feel pain, minor injuries in this area may not be immediately recognized and may develop into extensive ulcerations. Once infection occurs, further complications such as progressive destruction of underlying bones may follow and may necessitate amputation. In rare cases, the disease is accompanied with nerve deafness and muscle wasting. Autonomic disturbance, if present, appears as anhidrosis, a sweating abnormality. Examinations of the nerve structure and function showed signs of neuronal degeneration such as a marked reduction in the number of myelinated fibers and axonal loss. Sensory neurons lose the ability to transmit signals, while motor neurons has reduced ability to transmit signals.

Genes related to Hereditary sensory and autonomic neuropathy Type 1:

Mutations in the SPTLC1 gene cause hereditary sensory neuropathy type 1. The SPTLC1 gene provides instructions for making one part (subunit) of an enzyme called serine palmitoyltransferase (SPT). The SPT enzyme is involved in making certain fats called sphingolipids. Sphingolipids are important components of cell membranes and play a role in many cell functions.

SPTLC1 gene mutations reduce the amount of SPTLC1 subunit that is produced and result in an SPT enzyme with decreased function. A lack of functional SPT enzyme leads to a decrease in sphingolipid production and a harmful buildup of certain byproducts. Sphingolipids are found in myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. A decrease in sphingolipids disrupts the formation of myelin, causing nerve cells to become less efficient and eventually die. When sphingolipids are not made, an accumulation of toxic byproducts can also lead to nerve cell death. This gradual destruction of nerve cells results in loss of sensation and muscle weakness in people with hereditary sensory neuropathy type 1.

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.

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.

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.

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.

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.

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.

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

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.

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.

Distal spinal muscular atrophy type 2 (DSMA2), also known as Jerash type distal hereditary motor neuropathy (HMN-J) — is a very rare childhood-onset genetic disorder characterised by progressive muscle wasting affecting lower and subsequently upper limbs. The disorder has been described in Arab inhabitants of Jerash region in Jordan as well as in a Chinese family.

The condition is linked to a genetic mutation in the "SIGMAR1" gene on chromosome 19 (locus 19p13.3) and is likely inherited in an autosomal recessive manner.

About 1 in 4,000 children in the United States will develop mitochondrial disease by the age of 10 years. Up to 4,000 children per year in the US are born with a type of mitochondrial disease. Because mitochondrial disorders contain many variations and subsets, some particular mitochondrial disorders are very rare.

The average number of births per year among women at risk for transmitting mtDNA disease is estimated to approximately 150 in the United Kingdom and 800 in the United States.

This disease is endemic in Portuguese locations Póvoa de Varzim and Vila do Conde (Caxinas), with more than 1000 affected people, coming from about 500 families, where 70% of the people develop the illness. ll the analysed Portuguese families presented the same haplotype (haplotype I) associated with the Met 30 mutation. In northern Sweden, more specifically Piteå, Skellefteå and Umeå, 1.5% of the population has the mutated gene. There are many other populations in the world who exhibit the illness after having developed it independently.

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.

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.

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"