Exposure of spermatozoa to lifestyle, environmental and/or occupational hazards may increase the risk of aneuploidy. Cigarette smoke is a known aneugen (aneuploidy inducing agent). It is associated with increases in aneuploidy ranging from 1.5 to 3.0-fold. Other studies indicate factors such as alcohol consumption, occupational exposure to benzene, and exposure to the insecticides fenvalerate and carbaryl also increase aneuploidy.

Microdeletions in the Y chromosome have been found at a much higher rate in infertile men than in fertile controls and the correlation found may still go up as improved genetic testing techniques for the Y chromosome are developed.

Much study has been focused upon the "azoospermia factor locus" (AZF), at Yq11. A specific partial deletion of AZFc called "gr/gr deletion" is significantly associated with male infertility among Caucasians in Europe and the Western Pacific region.

Additional genes associated with spermatogenesis in men and reduced fertility upon Y chromosome deletions include RBM, DAZ, SPGY, and TSPY.

Lujan–Fryns syndrome is a rare X-linked dominant syndrome, and is therefore more common in males than females. Its prevalence within the general population has not yet been determined.

Human trisomies compatible with live birth, other than Down syndrome (trisomy 21), are Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13). Complete trisomies of other chromosomes are usually not viable and represent a relatively frequent cause of miscarriage. Only in rare cases of a mosaicism, the presence of a normal cell line, in addition to the trisomic cell line, may support the development of a viable trisomy of the other chromosomes.

The mechanism of mutation is not different for Y-chromosome microdeletion. However, the ability to repair it differs from other chromosomes. The human Y chromosome is passed directly from father to son, and is not protected against accumulating copying errors, whereas other chromosomes are error corrected by recombining genetic information from mother and father. This may leave natural selection as the primary repair mechanism for the Y chromosome.

Miller-Dieker occurs in less than one in 100000 people and can occur in all races.

Ring chromosome 14 syndrome is extremely rare, the true rate of occurrence is unknown (as it is "less than" 1 per 1,000,000), but there are at least 50 documented cases in the literature.

As its name indicates, a person with the syndrome has one Y chromosome and four X chromosomes on the 23rd pair, thus having 49 chromosomes rather than the normal 46. As with most categories of aneuploidy disorders, 49,XXXXY syndrome is often accompanied by intellectual disability. It can be considered a form of 47, XXY Klinefelter syndrome, or a variant of it.

It is genetic but not hereditary. This means that while the genes of the parents cause the syndrome, there is a small chance of more than one child having the syndrome. The probability of inheriting the disease is about 1%.

The individuals with this syndrome are males, but 49, XXXXX also exists with similar characteristics.

Most individuals with this condition do not survive beyond childhood. Individuals with MDS usually die in infancy and therefore do not live to the age where they can reproduce and transmit MDS to their offspring.

As the syndrome is due to a chromosomal non-disjunction event, the recurrence risk is not high compared to the general population. There has been no evidence found that indicates non-disjunction occurs more often in a particular family.

Currently, research is focusing on identifying the role of the genes on 18p and 18q in causing the signs and symptoms associated with deletions of 18p and/or 18q. This will ultimately enable predictive genotyping.Thus far, several genes on chromosome 18 have been linked with a phenotypic effect.

TGIF - Mutations and deletions of this gene, which is located on18p, have been associated with holoprosencephaly. Penetrance is incomplete, meaning that a deletion of one copy of this gene is not in and of itself sufficient to cause holoprosencephaly. Ten to fifteen percent of people with 18p- have holoprosencephaly, suggesting that other genetic and environmental facts play a role in the etiology of holoprosencephaly in these individuals.

TCF4 – In 2007, deletions of or point mutations in this gene, which is located on 18q, were identified as the cause of Pitt-Hopkins disease. This is the first gene that has been definitively shown to directly cause a clinical phenotype when deleted. If a deletion includes the TCF4 gene (located at 52,889,562-52,946,887), features of Pitt-Hopkins may be present, including abnormal corpus callosum; short neck; small penis; accessory and wide-spaced nipples; broad or clubbed fingers; and sacral dimple. Those with deletions inclusive of TCF4 have a significantly more severe cognitive phenotype.

TSHZ1 - Point mutations and deletions of this gene, located on 18q, are linked with congenital aural atresia Individuals with deletions inclusive of this gene have a 78% chance of having aural atresia.

"Critical regions" – Recent research has narrowed the critical regions for four features of the distal 18q- phenotype down to a small segment of distal 18q, although the precise genes responsible for those features remain to be identified.

"Haplolethal Regions" - There are two regions on chromosome 18 that has never been found to be deleted. They are located between the centromere and 22,826,284 bp (18q11.2) and between 43,832,732 and 45,297,446 bp (18q21.1). It is hypothesized that there are genes in these regions that are lethal when deleted.

An individual exhibiting intellectual disability and other symptoms similar to LFS was found to have a terminal deletion of the subtelomeric region in the short arm of chromosome 5. Deletion of this area of chromosome 5 is associated with intellectual disability, psychotic behavior, autism, macrocephaly and hypernasal-like speech, as well as the disorder Cri du chat syndrome. Fryns (2006) suggests a detailed examination of chromosome 5 with FISH should be performed as part of the differential diagnosis of LFS.

Mutations in the "UPF3B" gene, also found on the X chromosome, are another cause of X-linked intellectual disability. "UPF3B" is part of the nonsense-mediated mRNA decay (NMD) complex, which performs mRNA surveillance, detecting mRNA sequences that have been erroneously truncated (shortened) by the presence of nonsense mutations. Mutations in "UPF3B" alter and prevent normal function of the NMD pathway, resulting in translation and expression of truncated mRNA sequences into malfunctioning proteins that can be associated with developmental errors and intellectual disability. Individuals from two families diagnosed with LFS and one family with FGS were found to have mutations in "UPF3B", confirming that the clinical presentations of the different mutations can overlap.

The syndrome primarily affects young males. Preliminary studies suggest that prevalence may be 1.8 per 10,000 live male births. 50% of those affected do not live beyond 25 years of age, with deaths attributed to the impaired immune function.

Affected individuals have a somewhat shortened lifespan. The maximum described lifespan is 67 years. Adults with 13q deletion syndrome often need support services to maintain their activities of daily living, including adult day care services or housing services.

The estimated prevalence of Jacobsen syndrome is believed to be approximately 1 out of every 100,000 births. For reasons unknown females are twice as likely to have Jacobsen Syndrome than males. No preference for any race or ethnicity has been reported so far.

Human genetic disorders can be caused by ring chromosome formation. Although ring chromosomes are very rare, they have been found in all human chromosomes. Symptoms seen in patients carrying ring chromosomes are more likely to be caused by the deletion of genes in the telomeric regions of affected chromosomes, rather than by the formation of a ring structure itself. Almost all ring chromosome syndromes feature marked growth delay.

Ring chromosomes can be inherited or sporadic. Mosaicism is common and affects the severity of the condition. Location of fusion also affects severity due to loss of differing amounts of genetic material from the ends of chromosomes.

Disorders arising from the formation of a ring chromosome include:

In order for a chromosome to form a ring, both ends of the chromosome are often missing, enabling the broken ends to fuse together. In rare cases, the telomeres at the ends of a chromosome fuse without any loss of genetic material, which results in a normal phenotype.

Complex rearrangements, including segmental microdeletions and microduplications, have been seen in numerous ring chromosomes, providing important clues regarding the mechanisms of their formation.

Small supernumary rings can also form, resulting in a partial trisomy.

Ring chromosomes are unstable during cell division and can form interlocking or fused rings.

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

Patients have an essentially normal life expectancy but require regular medical follow-up.

Trisomy 22 is a chromosomal disorder in which there are three copies of chromosome 22 rather than two. It is a frequent cause of spontaneous abortion during the first trimester of pregnancy. Progression to the second trimester and live birth are rare. This disorder is found in individuals with an extra copy or a variation of chromosome 22 in some or all cells of their body. There are many kinds of disorders associated with Trisomy 22:

Emanuel Syndrome is named after the genetic contributions made by researcher Dr. Beverly Emanuel. This condition is assigned to individuals born with an unbalanced 11/22 translocation. That is, a fragment of chromosome 11 is moved, or translocated, to chromosome 22.

22q11 Deletion Syndrome is a rare condition which occurs in approximately 1 in 4000 births. This condition is identified when a band in the q11.2 section of the arm of chromosome 22 is missing or deleted. This condition has several different names: 22q11.2 Deletion Syndrome, Velocardiofacial syndrome, DiGeorge Syndrome, Conotruncal Anomaly Face syndrome, Opitz G/BBB Syndrome, and Cayler Cardiofacial Syndrome. The effects of this disorder are different in each individual but similarities exist such as heart defects, immune system problems, a distinctive facial appearance, learning challenges, cleft palate, hearing loss, kidney problems, hypocalcemia, and sometimes psychiatric issues.

22q11 microduplication syndrome is the opposite of the 22q11 deletion syndrome: in this condition, a band of q.11.2 section of chromosome 22 is duplicated. Individuals carrying this deficiency are relatively “normal” as in they don’t possess any major birth defects or major medical illnesses. This microduplication is more common than the deletion; this might be due to the milder phenotype of the individuals.

Phelan-McDermid Syndrome / 22q13 Deletion Syndrome is a condition caused by the deletion of the tip of the q arm on chromosome 22. Most individuals with this disorder experience cognitive delays; low muscle tone; and sleeping, eating, and behavioural issues.

Chromosome Ring 22 is a rare disorder caused by the break and re-join of both ends of chromosome 22, forming a ring. The effects on the individual with this disorder are dependent on the amount of genetic information lost during the break/re-join. Major characteristics for this disorder are intellectual disability, muscle weakness and lack of coordination.

Cat Eye Syndrome / Schmid Fraccaro Syndrome is a condition caused by a partial trisomy or tetrasomy in chromosome 22. A small extra chromosome is found, made up of the top half of chromosome 22 and a portion of the q arm at the q11.2 break. This chromosome can be found three or four times. This syndrome is referred as “Cat Eye” due to the eye appearance of reported affected individuals who have coloboma of the iris; however, this feature is only seen in about half of the cases.

Mosaic trisomy 22 is a disorder in which an extra chromosome 22 is found only in some cells of the body. The severity of each case is determined by the number of cells with this extra copy. Some characteristics of individuals with this condition are cardiac abnormalities, growth retardation, mental delay, etc.

Complete Trisomy 22 is in contrast with Mosaic trisomy 22; this disorder is characterized by an extra copy of chromosome 22 which is found in each cell of the body of the affected individual. These cases are very rare, and most of the affected individuals die before birth or shortly after.

Jacobsen Syndrome is a rare chromosomal disorder resulting from deletion of genes from chromosome 11 that includes band 11q24.1. It is a congenital disorder. Since the deletion takes place on the q arm of chromosome 11, it is also called 11q terminal deletion disorder. The deletion may range from 5 million to 16 million deleted DNA base pairs. The severity of symptoms depends on the number of deletions. The more deletions there are more severe the symptoms are likely to be. People with Jacobsen syndrome have serious intellectual disabilities, dysmorphic features, delayed development and a variety of physical problems including heart defects. Research shows that almost 88.5% of people with Jacobsen Syndrome have a bleeding disorder called Paris-Trousseau syndrome. [ Jacobsen Syndrome is catastrophic in 1 out of every 5 cases, since children usually die within the first 2 years of life due to heart complications.

47,XYY is not inherited, but usually occurs as a random event during the formation of sperm cells. An incident in chromosome separation during anaphase II (of meiosis II) called nondisjunction can result in sperm cells with an extra copy of the Y-chromosome. If one of these atypical sperm cells contributes to the genetic makeup of a child, the child will have an extra Y-chromosome in each of the body's cells.

In some cases, the addition of an extra Y-chromosome results from nondisjunction during cell division during a post-zygotic mitosis in early embryonic development. This can produce 46,XY/47,XYY mosaics.

Ring 18 is a genetic condition caused by a deletion of the two tips of chromosome 18 followed by the formation of a ring-shaped chromosome. It was first reported in 1964.

49,XXXXY syndrome is an extremely rare aneuploidic sex chromosomal abnormality. It occurs in approximately 1 out of 85,000 to 100,000 males.

Around 1 in 1,000 boys are born with a 47,XYY karyotype. The incidence of 47,XYY is not known to be affected by the parents' ages.