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.

This syndrome, evenly spread in all ethnic groups, has a prevalence of 1-2 subjects per every 1000 males in the general population. 3.1% of infertile males have Klinefelter syndrome. The syndrome is also the main cause of male hypogonadism.

According to 2008 meta-analysis, the prevalence of the syndrome has increased over the past decades; however, this does not appear to be related to increased age of the mother at conception, as no increase was observed in the rates of other trisomies of sex chromosomes (XXX and XYY). The National Institutes of Health; however, state that older mothers might have a slightly increased risk.

Children with XXY differ little from other children. Although they can face problems during adolescence, often emotional and behavioral, and difficulties at school, most of them can achieve full independence from their families in adulthood. Most can lead a normal, healthy life.

The results of a study carried out on 87 Australian adults with the syndrome shows that those who have had a diagnosis and appropriate treatment from a very young age had a significant benefit with respect to those who had been diagnosed in adulthood.

There is research suggesting Klinefelter syndrome substantially decreases life expectancy among affected individuals, though the evidence is not definitive. A 1985 publication identified a greater mortality mainly due to diseases of the aortic valve, development of tumors and possible subarachnoid hemorrhages, reducing life expectancy by about 5 years. Later studies have reduced this estimated reduction to an average of 2.1 years. These results are still questioned data, are not absolute, and will need further testing.

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

With the Echidna, this kind of chromosomal arrangement is normal. In this species genetic sex differentiation works like this:

- 63 (XYXYXYXYX, male) and

- 64 (XXXXXXXXXX, female)

In mild cases, individuals with XXXY syndrome may lead a relatively good life. These individuals may face difficulties in communicating with others due to their language-based deficits. These deficits may make forming bonds with others difficult, but fulfilling relationships with others are still achievable. Those with higher scores in adaptive functioning are likely to have higher quality of life because they can be independent.

The condition 48,XXYY is not inherited; it usually occurs as a random event during the formation of reproductive cells (eggs and sperm). An error in cell division called nondisjunction results in a reproductive cell with an abnormal number of chromosomes. In 48,XXYY syndrome, the extra sex chromosomes almost always come from a sperm cell. Nondisjunction may cause a sperm cell to gain two extra sex chromosomes, resulting in a sperm cell with three sex chromosomes (one X and two Y chromosomes). If that sperm cell fertilizes a normal egg cell with one X chromosome, the resulting child will have two X chromosomes and two Y chromosomes in each of the body's cells.

In a small percentage of cases, 48,XXYY syndrome results from nondisjunction of the sex chromosomes in a 46,XY embryo very soon after fertilization has occurred. This means that an normal sperm cell with one Y chromosome fertilized a normal egg cell with one X chromosome, but right after fertilization nondisjunction of the sex chromosomes caused the embryo to gain two extra sex chromosomes, resulting in a 48,XXYY embryo.

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.

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.

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.

The general prognosis for girls with tetrasomy X is relatively good. Due to the variability of symptoms, some tetrasomy X girls are able to function normally, whereas others will need medical attention throughout their lives. Traditionally, treatment for tetrasomy X has been management of the symptoms and support for learning. Most girls are placed on estrogen treatment to induce breast development, arrest longitudinal growth, and stimulate bone formation to prevent osteoporosis. Speech, occupational, and physical therapy may also be needed depending on the severity of the symptoms.

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.

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.

Males with pathogenic "MECP2" mutations usually die within the first 2 years from severe encephalopathy, unless they have an extra X chromosome (often described as Klinefelter syndrome), or have somatic mosaicism.

Male fetuses with the disorder rarely survive to term. Because the disease-causing gene is located on the X chromosome, a female born with an MECP2 mutation on her X chromosome has another X chromosome with an ostensibly normal copy of the same gene, while a male with the mutation on his X chromosome has no other X chromosome, only a Y chromosome; thus, he has no normal gene. Without a normal gene to provide normal proteins in addition to the abnormal proteins caused by a MECP2 mutation, the XY karyotype male fetus is unable to slow the development of the disease, hence the failure of many male fetuses with a MECP2 mutation to survive to term.

Females with a MECP2 mutation, however, have a non-mutant chromosome that provides them enough normal protein to survive longer. Research shows that males with Rett syndrome may result from Klinefelter's syndrome, in which the male has an XXY karyotype. Thus, a non-mutant "MECP2" gene is necessary for a Rett's-affected embryo to survive in most cases, and the embryo, male or female, must have another X chromosome.

There have, however, been several cases of 46,XY karyotype males with a MECP2 mutation (associated with classical Rett syndrome in females) carried to term, who were affected by neonatal encephalopathy and died before 2 years of age. The incidence of Rett syndrome in males is unknown, partly owing to the low survival of male fetuses with the Rett syndrome-associated MECP2 mutations, and partly to differences between signs caused by MECP2 mutations and those caused by Rett's.

Females can live up to 40 years or more. Laboratory studies on Rett syndrome may show abnormalities such as:

- EEG abnormalities from 2 years of age

- atypical brain glycolipids

- elevated CSF levels of "beta"-endorphin and glutamate

- reduction of substance P

- decreased levels of CSF nerve growth factors

A high proportion of deaths are abrupt, but most have no identifiable cause; in some instances death is the result most likely of:

- spontaneous brainstem dysfunction

- cardiac arrest, likely due to long QT syndrome, ventricular tachycardia or other arrhythmias

- seizures

- gastric perforation

Reversal of symptoms have been reported in between 15% to 22% of cases. The causes of this reversal are still under investigation but have been reported in both males and females.

Reversal appears to be associated with 14 of the known gene defects linked to KS/CHH. The study suggests no obvious gene defect showing a tendency to allow reversal. There is a suggestion that the TAC3 and TACR3 mutations might allow for a slightly higher chance of reversal, but the numbers involved are too low to confirm this. The ANOS1 mutations appear to be least likely to allow reversal with to date only one recorded instance in medical literature. Even male patients who previous had micro-phallus or cryptorchidism have been shown to undergo reversal of symptoms.

The reversal might not be permanent and remission can occur at any stage; the paper suggests that this could be linked to stress levels. The paper highlighted a reversal case that went into remission but subsequently achieved reversal again, strongly suggesting an environmental link.

Reversal cases have been seen in cases of both KS and normosmic CHH but appear to be less common in cases of KS (where the sense of smell is also affected). A paper published in 2016 agreed with the theory that there is a strong environmental or epigenetic link to the reversal cases. The precise mechanism of reversal is unclear and is an area of active research.

Reversal would be apparent if testicular development was seen in men while on testosterone therapy alone or in women who menstruate or achieved pregnancy while on no treatment. To date there have been no recorded cases of the reversal of anosmia found in Kallmann syndrome cases.

To date at least twenty five different genes have been implicated in causing Kallmann syndrome or other forms of HH through a disruption in the production or activity of GnRH. These genes involved cover all forms of inheritance and no one gene defect has been shown to be common to all cases which makes genetic testing and inheritance prediction difficult.

The number of genes known to cause cases of KS / CHH is still increasing. In addition it is thought that some cases of KS / CHH are caused by two separate gene defects occurring at the same time. Around 50% of cases have an unknown genetic origin.

Some of the genes known to be involved in cases of KS / CHH are listed in the Online Mendelian Inheritance in Man ((OMIM)) table at the end of this article.

The prognosis varies widely from case to case, depending on the severity of the symptoms. However, almost all people reported with Aicardi syndrome to date have experienced developmental delay of a significant degree, typically resulting in mild to moderate to profound intellectual disability. The age range of the individuals reported with Aicardi syndrome is from birth to the mid 40s.

There is no cure for this syndrome.

Worldwide prevalence of Aicardi Syndrome is estimated at several thousand, with approximately 900 cases reported in the United States.

XX male syndrome is a rare congenital condition where an individual with a female genotype has phenotypically male characteristics that can vary between cases. In 90% of these individuals the syndrome is caused by unequal crossing over between X and Y chromosomes during meiosis in the father, and results in the X chromosome containing the SRY gene, as opposed to the Y chromosome where it is normally found. When the X with the SRY gene combines with a normal X from the mother during fertilization, the result is an XX male. Less common are SRY-negative XX males which can be caused by a mutation in an autosomal or X chromosomal gene. The masculinization of XX males is variable.

This syndrome is diagnosed through various detection methods and occurs in approximately 1:20 000 newborn males, making it less common than Klinefelter syndrome. Treatment is medically unnecessary, although some individuals choose to undergo treatments to make them appear more male or female. It is also called de la Chapelle syndrome, for Albert de la Chapelle, who characterized it in 1972.

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

The overall incidence is ~1/42,000 to 1/50,000 people. Types I and II are the most common types of the syndrome, whereas types III and IV are rare. Type 4 is also known as Waardenburg‐Shah syndrome (association of Waardenburg syndrome with Hirschsprung disease).

Type 4 is rare with only 48 cases reported up to 2002.

About 1 in 30 students in schools for the deaf have Waardenburg syndrome. All races and sexes are affected equally. The highly variable presentation of the syndrome makes it difficult to arrive at precise figures for its prevalence.

The degree to which individuals with XX male syndrome develop the male phenotype is variable, even among SRY-positive individuals. A completely male phenotype usually develops in the presence of the SRY gene but, in some cases, the presence of the SRY gene can result in internal and/or external genitalia ambiguities. Normal XX females undergo X inactivation during which one copy of the X chromosome is silenced. It is thought that X inactivation in XX males may account for the genital ambiguities and incomplete masculinization seen in SRY-positive XX males. The X chromosome with the SRY gene is preferentially chosen to be the active X chromosome 90% of the time, which is why a complete male phenotype is often seen in SRY-positive XX males. In the remaining 10%, X inactivation spreads to include a portion of the SRY gene, resulting in incomplete masculinization.

Masculinization of SRY-negative XX males is dependent upon which genes have mutations and at what point in development these mutations occur.

Currently there is no cure for Rett syndrome. Treatment is directed towards improving function and addressing symptoms throughout life. A multi-disciplinary team approach is typically used to treat the person throughout life. This team may include primary care physician, physical therapist, occupational therapist, speech-language pathologist, nutritionist, and support services in academic and occupational settings.

Treatment of Rett syndrome includes:

Because of the increased risk of sudden cardiac death, when long QT syndrome is found on an annual screening EKG it is treated with an anti-arrhythmic such as a beta-blocker. There is some evidence that phenytoin may be more effective than a beta-blocker.

Waardenburg syndrome is a rare genetic disorder most often characterized by varying degrees of deafness, minor defects in structures arising from the neural crest, and pigmentation changes. It was first described in 1951. The syndrome was later found to have four types. For example, type II was identified in 1971, to describe cases where dystopia canthorum was not present. Some types are now split into subtypes, based upon the gene responsible for the condition.

Males are twice as likely as females to have this characteristic, and it tends to run in families. In its non-symptomatic form, it is more common among Asians and Native Americans than among other populations, and in some families there is a tendency to inherit the condition unilaterally, that is, on one hand only.

The presence of a single transverse palmar crease can be, but is not always, a symptom associated with abnormal medical conditions, such as fetal alcohol syndrome, or with genetic chromosomal abnormalities, including Down Syndrome (chromosome 21), cri du chat syndrome (chromosome 5), Klinefelter syndrome, Wolf-Hirschhorn Syndrome, Noonan syndrome (chromosome 12), Patau syndrome (chromosome 13), IDIC 15/Dup15q (chromosome 15), Edward's syndrome (chromosome 18), and Aarskog-Scott syndrome (X-linked recessive), or autosomal recessive disorder, such as Leaukocyte adhesion deficiency-2 (LAD2). A unilateral single palmar crease was also reported in a case of chromosome 9 mutation causing Nevoid basal cell carcinoma syndrome and Robinow syndrome. It is also sometimes found on the hand of the affected side of patients with Poland Syndrome, and craniosynostosis.