Congenital distal spinal muscular atrophy is caused by a mutation of the "TRPV4" gene found on the 12q23-12q24.1. The mutation causes an affected individual to have lower levels of "TRPV4" expression. This deficiency can lead to abnormal osmotic regulation. Congenital dSMA is genetically heterogeneous, meaning a mutation on this gene can cause a plethora of other phenotypically related or phenotypically unrelated diseases depending on the region that is mutated.

The outlook for individuals with EDS depends on the type of EDS they have. Symptoms vary in severity, even within one sub-type, and the frequency of complications changes individually. Some people have negligible symptoms while others are severely restricted in their daily life. Extreme joint instability, chronic musculoskeletal pain, degenerative joint disease, frequent injuries, and spinal deformities may limit mobility. Severe spinal deformities may affect breathing. In the case of extreme joint instability, dislocations may result from simple tasks such as rolling over in bed or turning a doorknob. Secondary conditions such as autonomic dysfunction or cardiovascular problems, occurring in any type, can affect prognosis and quality of life. Severe mobility-related disability is seen more often in Hypermobility-type than in Classical-type or Vascular-type.

Although all types are potentially life-threatening, the majority of individuals will have a normal lifespan. However, those with blood vessel fragility have a high risk of fatal complications. Arterial rupture is the most common cause of sudden death in EDS. Spontaneous arterial rupture most often occurs in the second or third decade, but can occur at any time. The median life-expectancy in the population with Vascular EDS is 48 years.

Prognosis strongly depends on which subtype of disease it is. Some are deadly in infancy but most are late onset and mostly manageable.

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.

Mäkelä-Bengs et al. (1997,1998) performed a genome-wide screening and linkage analysis and assigned the LCCS locus to a defined region of 9q34.

DSMA1 is usually fatal in early childhood. The patient, normally a child, suffers a progressive degradation of the respiratory system until respiratory failure. There is no consensus on the life expectancy in DSMA1 despite a number of studies being conducted. A small number of patients survive past two years of age but they lack signs of diaphragmatic paralysis or their breathing is dependent on a ventilation system.

Life expectancy for individuals with hypochondroplasia is normal; the maximum height is about 147 cm or 4.8 ft.

X-linked spinal muscular atrophy type 2 (SMAX2, XLSMA), also known as arthrogryposis multiplex congenita X-linked type 1 (AMCX1), is a rare neurological disorder involving death of motor neurons in the anterior horn of spinal cord resulting in generalised muscle wasting (atrophy). The disease is caused by a mutation in "UBA1" gene and is passed in a X-linked recessive manner by carrier mothers to affected sons.

Affected babies have general muscle weakness, weak cry and floppy limbs; consequently, the condition is usually apparent at or even before birth. Symptoms resemble the more severe forms of the more common spinal muscular atrophy (SMA); however, SMAX2 is caused by a different genetic defect and only genetic testing can correctly identify the disease.

The disorder is usually fatal in infancy or early childhood due to progressive respiratory failure, although survival into teenage years have been reported. As with many genetic disorders, there is no known cure to SMAX2. Appropriate palliative care may be able to increase quality of life and extend lifespan.

Congenital distal spinal muscular atrophy (congenital dSMA) is a hereditary genetic condition characterized by muscle wasting (atrophy), particularly of distal muscles in legs and hands, and by early-onset contractures (permanent shortening of a muscle or joint) of the hip, knee, and ankle. Affected individuals often have shorter lower limbs relative to the trunk and upper limbs. The condition is a result of a loss of anterior horn cells localized to lumbar and cervical regions of the spinal cord early in infancy, which in turn is caused by a mutation of the "TRPV4" gene. The disorder is inherited in an autosomal dominant manner. Arm muscle and function, as well as cardiac and respiratory functions are typically well preserved.

In terms of cause this disorder is transmitted as an autosomal dominant trait affecting the "FGFR3" gene on chromosome 4p16.3, there is currently no cure for this condition.

There have been 30 cases of Marden-Walker Syndrome reported since 1966. The first case of this was in 1966 a female infant was diagnosed with blepharophimosis, joint contractures, arachnodactyly and growth development delay. She ended up passing at 3 months due to pneumonia.

Lethal congenital contracture syndrome 1 (LCCS1), also called Multiple contracture syndrome, Finnish type, is an autosomal recessive genetic disorder characterized by total immobility of a fetus, detectable at around the 13th week of pregnancy. LCCS1 invariably leads to prenatal death before the 32nd gestational week. LCCS1 is one of 40 Finnish heritage diseases. It was first described in 1985 and since then, approximately 70 cases have been diagnosed.

The disease has only been identified as distinct from SMA recently, so research is still experimental, taking place mostly in animal models. Several therapy pathways have been devised which include gene therapy, whereby an "IGHMBP2" transgene is delivered to the cell using a viral vector; small-molecule drugs like growth factors (e.g., IGF-1 and VEGF) or olesoxime; and transplantation of healthy motor neurons grown "in vitro" from the patient's stem cells. Studies in amyotrophic lateral sclerosis are also considered helpful because the condition is relatively similar to SMARD1.

Overall, the prognosis for patients with NOMID is not good, though many (80%) live into adulthood, and a few appear to do relatively well. They are at risk for leukemia, infections, and some develop deposits of protein aggregated called amyloid, which can lead to kidney failure and other problems. The neurologic problems are most troubling. The finding that other diseases are related and a better understanding of where the disease comes from may lead to more effective treatments.

Bethlem myopathy is an autosomal dominant myopathy, classified as a congenital form of muscular dystrophy, that is caused by a mutation in one of the three genes coding for type VI collagen. These include COL6A1, COL6A2, and COL6A3.

Spinal muscular atrophy with lower extremity predominance (SMA-LED) is an extremely rare neuromuscular disorder of infants characterised by severe progressive muscle atrophy which is especially prominent in legs.

The disorder is associated with a genetic mutation in the "DYNC1H1" gene (the gene responsible also for one of the axonal types of Charcot–Marie–Tooth disease) and is inherited in an autosomal dominant manner. As with many genetic disorders, there is no known cure to SMA-LED.

The condition was first described in a multi-generational family by Walter Timme in 1917. Its linkage to the "DYNC1H1" gene was discovered in 2010 by M. B. Harms, et al., who also proposed the current name of the disorder.

A 2006 study followed 223 patients for a number of years. Of these, 15 died, with a median age of 65 years. The authors tentatively concluded that this is in line with a previously reported estimate of a shortened life expectancy of 10-15 years (12 in their data).

The life expectancy in alpha-mannosidosis is highly variable. Individuals with early onset severe disease often do not survive beyond childhood, whereas those with milder disorders may survive well into adult life.

Behr syndrome is characterized by the association of early-onset optic atrophy with spinocerebellar degeneration resulting in ataxia, pyramidal signs, peripheral neuropathy and developmental delay.

Although it is an autosomal recessive disorder, heterozygotes may still manifest much attenuated symptoms. Autosomal dominant inheritance also being reported in a family. Recently a variant of OPA1 mutation with phenotypic presentation like Behr syndrome is also described. Some reported cases have been found to carry mutations in the OPA1, OPA3 or C12ORF65 genes which are known causes of pure optic atrophy or optic atrophy complicated by movement disorder.

While some reports suggest Gordon syndrome may be inherited in an X-linked dominant manner, most agree that it is inherited in an autosomal dominant manner with reduced expressivity and incomplete penetrance in females.

In autosomal dominant inheritance, having only one mutated copy of the disease-causing gene in each cell is sufficient to cause signs and symptoms of the condition. When an individual with an autosomal dominant condition has children, each child has a 50% (1 in 2) risk to inherit the mutated copy of the gene.

If a condition shows variable or reduced expressivity, it means that there can be a range in the nature and severity of signs and symptoms among affected individuals. Incomplete penetrance means that a portion of the individuals who carry the mutated copy of the disease-causing gene will not have any features of the condition.

Desmin-related myofibrillar myopathy is a subgroup of the myofibrillar myopathy diseases and is the result of a mutation in the gene that codes for desmin which prevents it from forming protein filaments, instead forming aggregates of desmin and other proteins throughout the cell.

Ehlers–Danlos syndrome is an inherited disorder estimated to occur in about 1 in 5,000 births worldwide. Initially, prevalence estimates ranged from 1 in 250,000 to 1 in 500,000 people, but these estimates were soon found to be vastly inaccurate as the disorder received further study and medical professionals became more adept at accurately diagnosing EDS. In fact, many experts now believe that Ehlers–Danlos syndrome may be far more common than the currently accepted estimate due to the wide range of severities with which the disorder presents.

The prevalence of the 13 types differs dramatically. The most commonly occurring is the Hypermobility type, followed by the Classical type. The other types of Ehlers–Danlos syndrome are very rare. For example, fewer than ten infants and children with the dermatosparaxis type have been described worldwide. Some types of Ehlers–Danlos are more common in Ashkenazi Jews. For example, the chance of being a carrier for type-VIIc Ehlers–Danlos is 1 in 248 in Ashkenazi Jews, whereas the prevalence of this mutation in the general population is 1 in 2,000.

This is a rare condition with an incidence estimated to be less than 1 in a million live births. About 100 cases have been reported worldwide. The bulk of cases are sporadic but familial forms with autosomal dominant transmission have also been described.

Singleton Merten Syndrome is an autosomal dominate genetic disorder with variable expression with an onset of symptoms during childhood.

Genetic disorders may also be complex, multifactorial, or polygenic, meaning they are likely associated with the effects of multiple genes in combination with lifestyles and environmental factors. Multifactorial disorders include heart disease and diabetes. Although complex disorders often cluster in families, they do not have a clear-cut pattern of inheritance. This makes it difficult to determine a person’s risk of inheriting or passing on these disorders. Complex disorders are also difficult to study and treat, because the specific factors that cause most of these disorders have not yet been identified. Studies which aim to identify the cause of complex disorders can use several methodological approaches to determine genotype-phenotype associations. One method, the genotype-first approach, starts by identifying genetic variants within patients and then determining the associated clinical manifestations. This is opposed to the more traditional phenotype-first approach, and may identify causal factors that have previously been obscured by clinical heterogeneity, penetrance, and expressivity.

On a pedigree, polygenic diseases do tend to "run in families", but the inheritance does not fit simple patterns as with Mendelian diseases. But this does not mean that the genes cannot eventually be located and studied. There is also a strong environmental component to many of them (e.g., blood pressure).

- asthma

- autoimmune diseases such as multiple sclerosis

- cancers

- ciliopathies

- cleft palate

- diabetes

- heart disease

- hypertension

- inflammatory bowel disease

- intellectual disability

- mood disorder

- obesity

- refractive error

- infertility