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.

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.

MMA mostly occurs in males between the ages of 15 and 25. Onset and progression are slow. MMA is seen most frequently in Asia, particularly in Japan and India; it is much less common in North America.

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.

The clinical course of BVVL can vary from one patient to another. There have been cases with progressive deterioration, deterioration followed by periods of stabilization, and deterioration with abrupt periods of increasing severity.

The syndrome has previously been considered to have a high mortality rate but the initial response of most patients to the Riboflavin protocol are very encouraging and seem to indicate a significantly improved life expectancy could be achievable. There are three documented cases of BVVL where the patient died within the first five years of the disease. On the contrary, most patients have survived more than 10 years after the onset of their first symptom, and several cases have survived 20–30 years after the onset of their first symptom.

Families with multiple cases of BVVL and, more generally, multiple cases of infantile progressive bulbar palsy can show variability in age of disease onset and survival. Dipti and Childs described such a situation in which a family had five children that had Infantile PBP. In this family, three siblings showed sensorineural deafness and other symptoms of BVVL at an older age. The other two siblings showed symptoms of Fazio-Londe disease and died before the age of two.

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.

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.

Fazio–Londe disease is linked to a genetic mutation in the "SLC52A3" gene on chromosome 20 (locus: 20p13). It is allelic and phenotypically similar to Brown–Vialetto–Van Laere syndrome.

The condition is inherited in an autosomal recessive manner.

The gene encodes the intestinal riboflavin transporter (hRFT2).

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.

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 disorder has been associated with various mutations in the SLC52A2 and "SLC52A3" genes. This gene is thought to be involved in transport of riboflavin.

BVVL is allelic and phenotypically similar to Fazio–Londe disease and likewise is inherited in an autosomal recessive manner.

Other causes may include:

- Diabetes mellitus

- Facial nerve paralysis, sometimes bilateral, is a common manifestation of sarcoidosis of the nervous system, neurosarcoidosis.

- Bilateral facial nerve paralysis may occur in Guillain–Barré syndrome, an autoimmune condition of the peripheral nervous system.

- Moebius syndrome is a bilateral facial paralysis resulting from the underdevelopment of the VII cranial nerve (facial nerve), which is present at birth. The VI cranial nerve, which controls lateral eye movement, is also affected, so people with Moebius syndrome cannot form facial expression or move their eyes from side to side. Moebius syndrome is extremely rare, and its cause or causes are not known.

The symptoms of MMA usually progress slowly for one to two years before reaching a plateau, and then remain stable for many years. Disability is generally slight. Rarely, the weakness progresses to the opposite limb. There is also a slowly progressive variant of MMA known as O'Sullivan-McLeod syndrome, which only affects the small muscles of the hand and forearm and has a slowly progressive course.

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 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"

Onset of first symptom has been reported between 1–12 years, with a mean age of onset at 8 years. Clinical course can be divided into early (< 6 yrs age, predominance of respiratory symptoms) and late course (6–20 years of age, predominance of motor symptoms on superior limbs). Progression to involve other cranial nerve muscles occurs over a period of months or years. In the Gomez review facial nerve was affected in all cases while hypoglossal nerve was involved in all except one case. Other cranial nerves involved were vagus, trigeminal, spinal accessory nerve, abducent, occulomotor and glossopharyngeal in this order. Corticospinal tract signs were found in 2 of the 14 patients.

The disease may progress to patient's death in a period as short as 9 months or may have a slow evolution or may show plateaus. Post mortem examination of cases have found depletion of nerve cells in the nuclei of cranial nerves. The histologic alterations found in patient with Fazio–Londe disease were identical to those seen in infantile-onset spinal muscular atrophy.

Strength may improve with administration of cholinesterase inhibitors.

Familial dysautonomia is a genetic disorder that affects the development and survival of certain nerve cells. The disorder disturbs cells in the autonomic nervous system, which controls involuntary actions such as digestion, breathing, production of tears, and the regulation of blood pressure and body temperature. It also affects the sensory nervous system, which controls activities related to the senses, such as taste and the perception of pain, heat, and cold. Familial dysautonomia is also called hereditary sensory and autonomic neuropathy, type III.

Problems related to this disorder first appear during infancy. Early signs and symptoms include poor muscle tone (hypotonia), feeding difficulties, poor growth, lack of tears, frequent lung infections, and difficulty maintaining body temperature. Older infants and young children with familial dysautonomia may hold their breath for prolonged periods of time, which may cause a bluish appearance of the skin or lips (cyanosis) or fainting. This breath-holding behavior usually stops by age 6. Developmental milestones, such as walking and speech, are usually delayed, although some affected individuals show no signs of developmental delay.

Additional signs and symptoms in school-age children include bed wetting, episodes of vomiting, reduced sensitivity to temperature changes and pain, poor balance, abnormal curvature of the spine (scoliosis), poor bone quality and increased risk of bone fractures, and kidney and heart problems. Affected individuals also have poor regulation of blood pressure. They may experience a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting. They can also have episodes of high blood pressure when nervous or excited, or during vomiting incidents. About one-third of children with familial dysautonomia have learning disabilities, such as a short attention span, that require special education classes. By adulthood, affected individuals often have increasing difficulties with balance and walking unaided. Other problems that may appear in adolescence or early adulthood include lung damage due to repeated infections, impaired kidney function, and worsening vision due to the shrinking size (atrophy) of optic nerves, which carry information from the eyes to the brain.

Type 3, familial dysautonomia (FD) or Riley-Day syndrome, is an autosomal recessive disorder seen predominantly in Jews of eastern European descent. Patients present with sensory and autonomic disturbances. Newborns have absent or weak suck reflex, hypotonia and hypothermia. Delayed physical development, poor temperature and motor incoordination are seen in early childhood. Other features include reduced or absent tears, depressed deep tendon reflexes, absent corneal reflex, postural hypotension and relative indifference to pain. Scoliosis is frequent. Intelligence remains normal. Many patients die in infancy and childhood. Lack of flare with intradermal histamine is seen. Histopathology of peripheral nerve shows reduced number of myelinated and non-myelinated axons. The catecholamine endings are absent.

Genes related to Hereditary sensory and autonomic neuropathy Type 3:

Mutations in the IKBKAP gene cause familial dysautonomia.

The IKBKAP gene provides instructions for making a protein called IKK complex-associated protein (IKAP). This protein is found in a variety of cells throughout the body, including brain cells.

Nearly all individuals with familial dysautonomia have two copies of the same IKBKAP gene mutation in each cell. This mutation can disrupt how information in the IKBKAP gene is pieced together to make a blueprint for the production of IKAP protein. As a result of this error, a reduced amount of normal IKAP protein is produced. This mutation behaves inconsistently, however. Some cells produce near normal amounts of the protein, and other cells—particularly brain cells—have very little of the protein. Critical activities in brain cells are probably disrupted by reduced amounts or the absence of IKAP protein, leading to the signs and symptoms of familial dysautonomia.

Central facial palsy can be caused by a lacunar infarct affecting fibers in the internal capsule going to the nucleus. The facial nucleus itself can be affected by infarcts of the pontine arteries.

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.

In terms of the prognosis of ulnar neuropathy early decompression of the nerve sees a return to normal ability (function). which should be immediate.Severe cubital tunnel syndrome tends to have a faster recovery process in individuals below the age of 70, as opposed to those above such an age. Finally, revisional surgery for cubital tunnel syndrome does not result well for those individuals over 50 years of age.

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.

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.

Distal hereditary motor neuronopathies (distal HMN, dHMN), sometimes also called distal hereditary motor neuropathies, are a genetically and clinically heterogeneous group of motor neuron diseases that result from genetic mutations in various genes and are characterized by degeneration and loss of motor neuron cells in the anterior horn of the spinal cord and subsequent muscle atrophy.

Although they can hardly be distinguished from hereditary motor and sensory neuropathies on the clinical level, dHMNs are considered a separate class of disorders.

The most common cause of diplegia in the legs is Cerebral Palsy. Paralysis of the legs may also be caused by trauma, injury, or genetics but this is very rare