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.

3-M syndrome is most often caused by a mutation in the gene CUL7, but can also be seen with mutations in the genes OBS1 and CCDC8 at lower frequencies. This is an inheritable disorder and can be passed down from parent to offspring in an autosomal recessive pattern. An individual must receive two copies of the mutated gene, one from each parent, in order to be have 3-M syndrome. An individual can be a carrier for the disorder if they inherit only one mutant copy of the gene, but will not present any of the symptoms associated with the disorder.

Since 3-M syndrome is a genetic condition there are no known methods to preventing this disorder. However, genetic testing on expecting parents and prenatal testing, which is a molecular test that screens for any problems in the heath of a fetus during pregnancy, may be available for families with a history of this disorder to determine the fetus' risk in inheriting this genetic disorder.

Recent research has been focused on studying large series of cases of 3-M syndrome to allow scientists to obtain more information behind the genes involved in the development of this disorder. Knowing more about the underlying mechanism can reveal new possibilities for treatment and prevention of genetic disorders like 3-M syndrome.

- One study looks at 33 cases of 3M syndrome, 23 of these cases were identified as CUL7 mutations: 12 being homozygotes and 11 being heterozygotes. This new research shows genetic heterogeneity in 3M syndrome, in contrast to the clinical homogeneity. Additional studies are still ongoing and will lead to the understanding of this new information.

- This study provides more insight on the three genes involved in 3M syndrome and how they interact with each other in normal development. It lead to the discovery that the CUL7, OBS1, and CCDC8 form a complex that functions to maintain microtubule and genomic integrity.

Qazi–Markouizos syndrome is a rare hereditary condition characterized by non-progressive, congenital hypotonia, severe intellectual disability, an increased proportion of type 2 muscle fibers, which additionally exhibited increased size, as well as dysharmonic skeletal maturation. To date, the molecular mechanism of Qazi–Markouizos syndrome, which is also known as Puerto Rican infant hypotonia syndrome, remains unknown.

Respiratory complications are often cause of death in early infancy.

It has been documented, to date, in more than 120 males (see Human Tafazzin ("TAZ") Gene Mutation & Variation Database). It is believed to be severely under-diagnosed and may be estimated to occur in 1 out of approximately 300,000 births. Family members of the Barth Syndrome Foundation and its affiliates live in the US, Canada, the UK, Europe, Japan, South Africa, Kuwait, and Australia.

Barth syndrome has been predominately diagnosed in males, although by 2012 a female case had been reported.

Marshall–Smith syndrome is not to be confused with:

- Marshall syndrome (aka.Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA syndrome, see also: Periodic fever syndrome)

- Sotos (like) syndrome

- Weaver-Smith syndrome (WSS)

With appropriate treatment and management, patients with Weaver syndrome appear to do well, both physically and intellectually, throughout their life and have a normal lifespan. Their adult height is normal as well.

Weaver syndrome and Sotos syndrome are often mistaken for one another due to their significant phenotypic overlap and similarities. Clinical features shared by both syndromes include overgrowth in early development, advanced bone age, developmental delay, and prominent macrocephaly. Mutations in the NSD1 gene may also be another cause for confusion. The NSD1 gene provides instructions for making a protein that is involved in normal growth and development. Deletions and mutations in the NSD1 gene is a common cause for patients with Sotos syndrome and in some cases for Weaver syndrome as well.

Features distinguishing Weaver syndrome from Sotos syndrome include broad forehead and face, ocular hypertelorism, prominent wide philtrum, micrognathia, deep-set nails, retrognathia with a prominent chin crease, increased prenatal growth, and a carpal bone age that is greatly advanced compared to metacarpal and phalangeal bone age.

Vici syndrome, also called immunodeficiency with cleft lip/palate, cataract, hypopigmentation and absent corpus callosum, is a rare autosomal recessive congenital disorder characterized by albinism, agenesis of the corpus callosum, cataracts, cardiomyopathy, severe psychomotor retardation, seizures, immunodeficiency, and recurrent severe infections. To date about 50 cases have been reported.

Vici syndrome is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.

The hypothesis of autosomal recessive inheritance of Vici syndrome was strengthened in 2002 with the clinical description of two new cases, one brother and one sister, by Chiyonobu et al.

Unlike other autoinflammatory disorders, patients with CANDLE do not respond to IL-1 inhibition treatment in order to stop the autoinflammatory response altogether. This suggests that the condition also involves IFN dysregulation.

Myhre syndrome is a rare genetic disorder inherited in an autosomal dominant fashion. It is caused by mutation in SMAD4 gene.

Patterson syndrome, also called pseudoleprechaunism, is an extremely rare syndrome, first mistaken as Donohue Syndrome (also known as Leprechaunism).

It is named for Dr. Joseph Hanan Patterson. It was described by Patterson and Watkins in 1962.

The pathogenesis and cause of the Patterson syndrome was unknown until 1981.

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

This disorder was first reported in 1981.

It has many similarities to LAPS Syndrome and they both arise from the same mutations in the SMAD4 gene. It is believed that they are the same syndrome.

Barth syndrome (BTHS), also known as 3-Methylglutaconic aciduria type II, is an X-linked genetic disorder. The disorder, which affects multiple body systems, is diagnosed almost exclusively in males. It is named after Dutch pediatric neurologist Masa Barth.

It is thought to have an estimated incidence of 1 in 75,000 people.

It is associated with LAMP2. The status of this condition as a GSD has been disputed.

Patterson syndrome is characterized by the patient's having an unusual facial look, similar to that caused by Leprechaunism. It primarily affects the connective tissue and the neuroendocrine system, giving rise to bronzed hyperpigmentation, cutis laxa of the hands and feet, bodily disproportion, severe mental retardation, and major bony deformities. Radiographs reveal a characteristic generalised skeletal dysplasia.

It comprises endocrine abnormality, hyperadrenocorticism, cushingoid features, and diabetes mellitus. One other case has shown premature adrenarche.

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

The most common known cause of the syndrome are mutations in the Proteasome Subunit, Beta Type, 8 (PSMB8) gene that codes for proteasomes that in turn break down other proteins. This occurs specifically when a mutation causes the homozygous recessive form to emerge. The mutated gene results in proteins not being degraded and oxidative proteins building up in cellular tissues, eventually leading to apoptosis, especially in muscle and fat cells.

A study conducted by Brehm et al. in November 2015 discovered additional mutations that can cause CANDLE syndrome, including PSMA3 (encodes α7), PSMB4 (encodes β7), PSMB9 (encodes β1i), and the proteasome maturation protein (POMP), with 8 mutations in total between them. An additional unknown mutation type in the original PSMB8 gene was also noted.

Although the genetic cause of Danon Disease is known, the mechanism of disease is not well understood. Danon disease involves a genetic defect (mutation) in a gene called LAMP2, which results in a change to the normal protein structure. While the function of the "LAMP2" gene is not well understood, it is known that LAMP2 protein is primarily located in small structures within cells called lysosomes.

Congenital fiber type disproportion (CFTD) is an inherited form of myopathy with small type 1 muscle fibers that may occur in a number of neurological disorders. It has a relatively good outcome and follows a stable course. While the exact genetics is unclear there is an association with TPM3, ACTA1 and SEPN1 gene mutations. It is a rare condition.

Congenital generalized lipodystrophy (also known as Berardinelli–Seip syndrome) is an extremely rare autosomal recessive skin condition, characterized by an extreme scarcity of fat in the subcutaneous tissues. It is a type of lipodystophy disorder where the magnitude of fat loss determines the severity of metabolic complications. Only 250 cases of the condition have been reported, and it is estimated that it occurs in 1 in 10 million people worldwide.