The expected future course of the disease depends on the subtype of the disease; the individual's sex, age, and initial symptoms; and the degree of disability the person has. Female sex, relapsing-remitting subtype, optic neuritis or sensory symptoms at onset, few attacks in the initial years and especially early age at onset, are associated with a better course.

The average life expectancy is 30 years from the start of the disease, which is 5 to 10 years less than that of unaffected people. Almost 40% of people with MS reach the seventh decade of life. Nevertheless, two-thirds of the deaths are directly related to the consequences of the disease. Suicide is more common, while infections and other complications are especially dangerous for the more disabled. Although most people lose the ability to walk before death, 90% are capable of independent walking at 10 years from onset, and 75% at 15 years.

Though for the most of the cases these diseases are still idiopathic, recent researchs have found the causes for some of them, making them not idiopathic anymore. There are currently two identified auto-antibodies and a genetic variant. The autoantibodies are anti-AQP4 and anti-MOG so far and the genetic variant is a mutation in the gene NR1H3.

The list of these diseases depends of the author, but usually are included:

- multiple sclerosis, normally defined by the dissemination in time and space of demyelinating lesions, with two (or sometimes three) clinical presentations:

- Relapsing-Onset multiple sclerosis, the most known and extended variant, normally consisting of two distinct clinical phases (Remitent-Recidivant, RRMS, and Secondary Progressive, SPMS)

- Progressive-Onset MS, most known as Primary progressive MS including a special genetic variant named rapidly progressive multiple sclerosis.

- Optic-spinal MS, or opticospinal, clinical and pathological variant of multiple sclerosis which often include visual symptoms and have a more severe course than typical MS. Though multiple scars (scleroses) are present in CNS, and they comply with the dissemination criteria, and sometimes is classified as clinically definite multiple sclerosis, currently is considered outside the scope of Multiple Sclerosis and inside the scope of Devic's disease, though it is uncertain if this applies to all cases. Also a variant affecting mainly the spinal cord and the cortex has been proposed

- Neuromyelitis optica (NMO), and its associated "spectrum of disorders" (NMOSD), currently considered a common syndrome for at least three separated diseases:, mainly produced by AQP4 autoimmune channelopathy, though other variants exists, some with anti-MOG and some others idiopathic. Some researchers think that there could exist an overlapping between Anti-NMDA receptor encephalitis cases and neuromyelitis optica or acute disseminated encephalomyelitis.

- Anti-MOG associated spectrum, often clinically presented as an anti-MOG autoimmune encephalomyelitis, but can also appear as negative NMO or atypical multiple sclerosis

- CRION (Chronic relapsing inflammatory optic neuritis): A distinct clinical entity from other inflammatory demyelinating diseases including multiple sclerosis (MS), neuromyelitis optica-immunoglobulin G (NMO-IgG) spectrum disease, and idiopathic relapsing optic neuritis.

- Acute disseminated encephalomyelitis or ADEM, a closely related disorder in which a known virus or vaccine triggers autoimmunity against myelin.

- Acute hemorrhagic leukoencephalitis, possibly a variant of Acute disseminated encephalomyelitis

- Balo concentric sclerosis, an unusual presentation of plaques forming concentrenic circles, which can sometimes get better spontaneously.

- Schilder disease or diffuse myelinoclastic sclerosis: is a rare disease that presents clinically as a pseudotumoural demyelinating lesion; and is more common in children.

- Marburg multiple sclerosis, an aggressive form, also known as malignant, fulminant or acute MS.

- Tumefactive multiple sclerosis: lesions whose size is more than 2 cm, with mass effect, oedema and/or ring enhancement

- Solitary sclerosis: This variant has been recently proposed (2012) by Mayo Clinic researches. though it was also reported by other groups more or less at the same time. It is defined as isolated demyelinating lesions which produce a progressive myelopathy similar to primary progressive MS, and is currently considered a synonym for tumefactive multiple sclerosis.

Some inflammatory conditions are associated with the presence of scleroses in the CNS. Optic neuritis (monophasic and recurrent) and Transverse myelitis (monophasic and recurrent)

As MS is an active field for research, the list is not closed or definitive. For example, some diseases like Susac's syndrome (MS has an important vascular component), leukoaraiosis, myalgic encephalomyelitis (aka chronic fatigue syndrome) or autoimmune variants of peripheral neuropathies like Guillain–Barré syndrome or progressive inflammatory neuropathy could be included assuming the autoimmune model. Also Leukodystrophy (which see) and its sub-conditions: Adrenoleukodystrophy and Adrenomyeloneuropathy could be in the list. Venous induced demyelination has also been proposed as a hypothetical MS variant produced by CCSVI.

Recent research has identified some possible new variants, like the possibility to separate primary progressive MS, PPMS, after recent findings seem to point that it is pathologically a very different disease.

Also an OPA1 variant and aKIR4.1 multiple sclerosis variant was reported in 2012 and later reported again, which could be considered a different disease (as Devic disease did before), and can represent up to a 47% of the MS cases. Finally, there exist some reports of an aquaporine-related multiple sclerosis, related to vegetal aquaporine proteins.

MS is more common in people who live farther from the equator, although exceptions exist. These exceptions include ethnic groups that are at low risk far from the equator such as the Samis, Amerindians, Canadian Hutterites, New Zealand Māori, and Canada's Inuit, as well as groups that have a relatively high risk close to the equator such as Sardinians, inland Sicilians, Palestinians and Parsis. The cause of this geographical pattern is not clear. While the north-south gradient of incidence is decreasing, as of 2010 it is still present.

MS is more common in regions with northern European populations and the geographic variation may simply reflect the global distribution of these high-risk populations. Decreased sunlight exposure resulting in decreased vitamin D production has also been put forward as an explanation. A relationship between season of birth and MS lends support to this idea, with fewer people born in the northern hemisphere in November as compared to May being affected later in life. Environmental factors may play a role during childhood, with several studies finding that people who move to a different region of the world before the age of 15 acquire the new region's risk to MS. If migration takes place after age 15, however, the person retains the risk of their home country. There is some evidence that the effect of moving may still apply to people older than 15.

A clinically isolated syndrome (CIS) is a clinical situation of an individual's first neurological episode, caused by inflammation or demyelination of nerve tissue. An episode may be monofocal, in which symptoms present at a single site in the central nervous system, or multifocal, in which multiple sites exhibit symptoms. CIS with enough paraclinical evidence can be considered as a clinical stage of Multiple Sclerosis (MS). It can also be retrospectively diagnosed as a kind of MS when more evidence is available.

Brain lesions associated with a clinically isolated syndrome may be indicative of several neurological diseases, like multiple sclerosis (MS) or Neuromyelitis optica. In order for such a diagnosis, multiple sites in the central nervous system must present lesions, typically over multiple episodes, and for which no other diagnosis is likely. A clinically definitive diagnosis of MS is made once an MRI detects lesions in the brain, consistent with those typical of MS. Other diagnostics include cerebrospinal fluid analysis and evoked response testing.

Currently it is considered that the best predictor of future development of clinical multiple sclerosis is the number of T2 lesions visualized by magnetic resonance imaging during the CIS. It is normal to evaluate diagnostic criteria against the "time to conversion to definite".

In 2001, the International Panel on the Diagnosis of Multiple Sclerosis issued the McDonald criteria, a revision of the previous diagnostic procedures to detect MS, known as the Poser criteria. "While maintaining the basic requirements of dissemination in time and space, the McDonald criteria provided specific guidelines for using findings on MRI and cerebrospinal fluid analysis to provide evidence of the second attack in those individuals who have had a single demyelinating episode and thereby confirm the diagnosis more quickly." Further revisions were issued in 2005.

Parents of a proband

- The parents of an affected individual are obligate heterozygotes and therefore carry one mutant allele.

- Heterozygotes (carriers) are asymptomatic.

Sibs of a proband

- At conception, each sibling of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.

- Once an at-risk sibling is known to be unaffected, the risk of his/her being a carrier is 2/3.

- Heterozygotes (carriers) are asymptomatic.

Offspring of a proband

- Offspring of a proband are obligate heterozygotes and will therefore carry one mutant allele.

- In populations with a high rate of consanguinity, the offspring of a person with GPR56-related BFPP and a reproductive partner who is a carrier of GPR56-related BFPP have a 50% chance of inheriting two GPR56 disease-causing alleles and having BFPP and a 50% chance of being carriers.

Other family members of a proband.

- Each sibling of the proband's parents is at a 50% risk of being a carrier

The 1996 definition of the clinical courses of MS (phenotypes) was updated on 2013 by an international panel (International Advisory Committee on Clinical Trials).

While the main classification in 1996 was the recovery from the attacks (this clinical feature separates RR from progressive), in the updated revision the main classification is the activity.

MS courses in the new revision are divided into active and non-active, and CIS, when is active on MRI, becomes a kind of RRMS (this, of course, must be retrospectively diagnosed after the CDMS conversion)

Some reviews describe CIS as "the prodromal stage of MS".

Benign hereditary chorea (BHC), also known as benign familial chorea, is a rare autosomal dominant neurogenetic syndrome. It typically presents in childhood with isolated chorea. Unlike other neurogenetic causes of chorea such as Huntington's disease, BHC is not progressive, and not associated with cognitive decline or psychiatric problems in the vast majority of cases.

BHC is caused by a single-nucleotide insertion mutation in "TITF1", which encodes thyroid transcription factor 1 (TTF-1). This gene is also known as NK2 homeobox 1 (NKX2-1)

In some cases, additional developmental abnormalities of lung and thyroid tissue are found in BHC, leading to the suggested alternative name "brain-lung-thyroid syndrome".

GM2-gangliosidosis, AB variant is a rare, autosomal recessive metabolic disorder that causes progressive destruction of nerve cells in the brain and spinal cord. It has a similar pathology to Sandhoff disease and Tay-Sachs disease. The three diseases are classified together as the GM2 gangliosidoses, because each disease represents a distinct molecular point of failure in the activation of the same enzyme, beta-hexosaminidase. AB variant is caused by a failure in the gene that makes an enzyme cofactor for beta-hexosaminidase, called the GM2 activator.

Patients are normal at birth and the syndrome manifests during childhood and puberty. The enchondromas affect the extremities and their distribution is asymmetrical. The most common sites of enchondromas are the metacarpal bones and phalanges of the hands. The feet are less commonly afflicted.

Disfigurations of the extremities are a result. Pathological fractures can arise in affected metaphyses and diaphyses of the long bones and are common (26%).

The risk for sarcomatous degeneration of enchondromas, hemangiomas, or lymphangiomas is 15-30% in the setting of Maffucci syndrome. Maffucci syndrome is associated with a higher risk of CNS, pancreatic, and ovarian malignancies. Multiple enchondromas may present in 3 disorders: Ollier disease, Maffucci syndrome, and metachondromatosis. It is important to make the distinction between these diseases, particularly Ollier disease and Maffucci syndrome. Ollier disease is more common than Maffucci syndrome, and presents with multiple enchondromas often in a unilateral distribution. However, hemangiomas and lymphangiomas are not seen in Ollier disease. Metachondromatosis demonstrates autosomal-dominant transmission and presents with both multiple osteochondromas and enchondromas.

In Ollier disease isolated enchondromas are present without the presence of hemangiomas.

Mutations in the GM2A gene cause GM2-gangliosidosis, AB variant. This condition is inherited in an autosomal recessive pattern.

The GM2A gene provides instructions for making a protein called the GM2 activator. This protein is required for the normal function of beta-hexosaminidase A, a critical enzyme in the nervous system that breaks down a lipid called GM2 ganglioside. If mutations in both alleles at this locus disrupt the activity of the GM2 activator, beta-hexosaminidase A cannot perform its normal function. As a result, gangliosides accumulate in the central nervous system until they interfere with normal biological processes. Progressive damage caused by buildup of gangliosides leads to the destruction of nerve cells.

GM2-gangliosidosis, AB variant is extremely rare. In contrast with both Tay-Sachs disease and Sandhoff disease, in which many mutant polymorphic alleles have been discovered, including pseudodeficiency alleles, very few GM2A mutations have been reported. When AB variant is reported, in often occurs with consanguineous parents or in genetically isolated populations.

GM2A is expressed in many tissues, and the GM2 activator protein has been reported to have other cellular functions. Because AB variant is so rarely diagnosed, it is likely that most mutations of GM2A are fatal at the embryionic or fetal stage of development in homozygotes and genetic compounds, and thus are never observed clinically.

Bilateral frontoparietal polymicrogyria (BFPP) is a genetic disorder with autosomal recessive inheritance that causes a cortical malformation. Our brain has folds in the cortex to increase surface area called gyri and patients with polymicrogyri have an increase number of folds and smaller folds than usual. Polymicrogyria is defined as a cerebral malformation of cortical development in which the normal gyral pattern of the surface of the brain is replaced by an excessive number of small, fused gyri separated by shallow sulci and abnormal cortical lamination. From ongoing research, mutation in GPR56, a member of the adhesion G protein-coupled receptor (GPCR) family, results in BFPP. These mutations are located in different regions of the protein without any evidence of a relationship between the position of the mutation and phenotypic severity. It is also found that GPR56 plays a role in cortical pattering.

The incidence of dominant optic atrophy has been estimated to be 1:50000 with prevalence as high as 1:10000 in the Danish population (Votruba, 1998). Dominant optic atrophy is inherited in an autosomal dominant manner. That is, a heterozygous patient with the disease has a 50% chance of passing on the disease to offspring, assuming his/her partner does not have the disease. Males and females are affected at the same rate. Although Kjer's has a high penetrance (98%), severity and progression of DOA are extremely variable even within the same family.

A prognosis for Alström syndrome is complicated because it widely varies. Any person that has the syndrome have different set of disorders. Permanent blindness, deafness, and Type 2 diabetes may occur. Liver and kidney failure can progressively get worse. The life expectancy is usually reduced and the patients rarely live past 50 years old.

Recent findings in genetic research have suggested that a large number of genetic disorders, both genetic syndromes and genetic diseases, that were not previously identified in the medical literature as related, may be, in fact, highly related in the genetypical root cause of the widely varying, phenotypically-observed disorders. Thus, Alstrom syndrome is a ciliopathy. Other known ciliopathies include primary ciliary dyskinesia, Bardet-Biedl syndrome, polycystic kidney and liver disease, nephronophthisis, Meckel-Gruber syndrome and some forms of retinal degeneration.

Once a diagnosis is made, the treatment is based on an individual’s clinical condition and may include standard management for autoimmunity and immunodeficiency. Hematopoietic stem cell transplantation has cured the immune abnormalities in one TRIANGLE patient, although the neurodevelopmental delay would likely remain. Investigators at the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health currently have clinical protocols to study new approaches to the diagnosis and treatment of this disorder.

Laurence–Moon syndrome (LMS) is a rare autosomal recessive genetic disorder associated with retinitis pigmentosa, spastic paraplegia, and mental disabilities.

Dominant optic atrophy is also known as autosomal dominant optic atrophy, Kjer type; Kjer optic atrophy; or, Kjer's autosomal dominant optic atrophy.

TRIANGLE disease is a rare genetic disorder of the immune system. TRIANGLE stands for “TPPII-related immunodeficiency, autoimmunity, and neurodevelopmental delay with impaired glycolysis and lysosomal expansion” where "TPP2" is the causative gene. This disease manifests as recurrent infection, autoimmunity, and neurodevelopmental delay. TRIANGLE disease was first described in a collaborative study by Dr. Helen C. Su from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Dr. Sophie Hambleton from the University of Newcastle and their collaborators in 2014. The disease was also described by the group of Ehl et al.

Adermatoglyphia is an extremely rare genetic disorder which causes a person to have no fingerprints. There are only four known extended families worldwide which are affected by this condition.

In 2011, the description of a case of a person from Switzerland lacking fingerprints as an isolated finding was published. The phenotype was mapped to chromosome 4q22. In the splice-site of a 3' exon of the gene for SMARCAD1-helicase, a point mutation was detected. It results in a shortened form of the skin-specific protein. The heterozygous mode of mutation suggests an autosomal dominant mode of inheritance.

Other conditions can cause a lack of fingerprints, but unlike them, adermatoglyphia has no other side effects. Mutations in helicases are involved in other rare genetic diseases, for instance Werner syndrome.

In northern Scandinavia, the prevalence of myotonia congenita has been estimated at 1:10,000.

Myotonia congenita is estimated to affect 1 in 1,000,000 people worldwide.

Screening for melanoma in FAMMM kindreds should begin at age 10 with a baseline total body skin examination including scalp, eyes, oral mucosa, genital area, and nail, as family members may develop melanoma in their early teens.

At Mayo Clinic, FAMMM patients with a confirmed mutation and family history of pancreatic cancer are offered screening with either high-resolution pancreatic protocol CT, MRI, or endoscopic ultrasound starting at age 50 or 10 years younger than the earliest family member with pancreas cancer. They are counseled on the lack of evidence-based data to support screening, and on the limitations of our current technology to detect a lesion at a stage amenable to therapy.

Dysplastic nevus syndrome (also known as "atypical mole syndrome (AMS)", "familial atypical multiple mole–melanoma (FAMMM) syndrome", "familial melanoma syndrome", and "B-K mole syndrome") is a cutaneous condition described in certain families, and characterized by unusual nevi and multiple inherited melanomas.

A Posterior Circulation Infarct (POCI) is a type of cerebral infarction affecting the posterior circulation supplying one side of the brain.

Posterior Circulation Stroke Syndrome (POCS) refers to the symptoms of a patient who clinically appears to have had a posterior circulation infarct, but who has not yet had any diagnostic imaging (e.g. CT Scan) to confirm the diagnosis.

It can cause the following symptoms:

- Cranial nerve palsy AND contralateral motor/sensory defect

- motor or sensory defect

- Eye movement problems (e.g.nystagmus)

- Cerebellar dysfunction

- Isolated homonymous hemianopia

It has also been associated with deafness.