49, XXXXY syndrome - Chromosome X.


The 49,XXXXY syndrome or chromosome XXXXY syndrome is a chromosomal process in children and boys that leads to intellectual disability, developmental delays, physical differences and infertility.

Signs and symptoms related to this process include mild or moderate intellectual disability; behavioral problems, such as irritability, difficulty in tolerating frustration, defiant behavior, and outbursts; hypotonia and coordination problems that delay the development of motor skills; physical differences such as short stature, radioulnar synostosis, hyperextensibility, anomalies in the elbow, clinodactyly in the fifth finger and flat feet; distinctive facial features including ocular hypertelorism, ascending palpebral fissures, epithelial folds, a flat nasal bridge and, in some cases, dental anomalies.

Other habitual characteristics include alterations in male sexual development, so that often individuals affected by this process have short and underdeveloped penis; testicles not descended, small that do not produce enough testosterone; scarce body hair; gynecomastia; and infertility.

This process is due to the presence of three additional X chromosomes in each cell. People usually have 46 chromosomes in each cell, two of which are the sex chromosomes. Women have two X chromosomes (46, XX) and males have one X and one Y chromosome (46, XY). Individuals with 49,XXXXY syndrome have the usual single Y chromosome, but have four copies of the X chromosome, for a total of 49 chromosomes in each cell; consequently, boys and men with 49,XXXXY syndrome have additional copies of multiple genes on the X chromosome. The activity of these additional genes affects many aspects of development, including sexual development before birth and at puberty. 

This syndrome is considered in some cases a variant of Klinefelter syndrome. Klinefelter syndrome affects male sexual development and can be associated with learning problems and problems with speech and language development. However, the characteristics of 49,XXXXY syndrome tend to be more severe than those of Klinefelter syndrome and affect more parts of the body.

The XXXXY syndrome is not inherited but occurs as a random event during the formation of reproductive cells in one of the parents. During cell division, an error called non-disjunction prevents the X chromosomes from being normally distributed among the reproductive cells as they are formed. Generally, as the cells divide, each oocyte gets a single X chromosome and each sperm receives an X chromosome or Y chromosome. However, due to lack of disjunction, an oocyte or sperm can also end up with three copies additional X chromosome. If an oocyte cell with three additional X chromosomes (XXXX) is fertilized by a sperm cell with a Y chromosome, the resulting child will have 49,XXXXY syndrome.

Tests performed in IVAMI: in IVAMI we perform the detection of the alterations associated with 49,XXXXY syndrome, by detecting additional X chromosomes.

Recommended samples: blood extracted with EDTA for separation of blood leukocytes, or card impregnated with dried blood sample (IVAMI can mail the card to deposit the blood sample).