48, XXXY syndrome - Chromosome X.


The 48,XXXY or XXXY syndrome, is a chromosomal condition that affects males and is characterized by intellectual disability, developmental delay, physical differences and infertility.

Signs and symptoms related to this process include mild intellectual disability with learning difficulties; problems with speech and communication; anxiety, poor attention span and diminished social skills; hypotonia and coordination problems that delay the development of motor skills; physical differences including radioulnar synostosis, hyperextensibility, elbow anomalies, clinodactyly in the fifth finger and flat foot. In some cases, affected individuals may have distinctive facial features, such as ocular hypertelorism, ascending palpebral fissures and epithelial folds. Other signs related to this process include penis shorter than usual; small testes that have not descended and that do not produce enough testosterone; scarce body hair; gynecomastia in some cases; and infertility in most cases.

This process is due to the presence of two 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). Children and boys with syndrome 48,XXXY have the usual single Y chromosome, but have three copies of the X chromosome. The activity of these additional genes affects many aspects of development, including sexual development before birth and 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 with speech and language development. However, the characteristics of syndrome 48, XXXY tend to be more severe than those of Klinefelter syndrome and affect more parts of the body.

The XXXY 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 egg gets a single X chromosome and each sperm receives an X chromosome or a chromosome. However, due to lack of disjunction, an egg or sperm can also end up with two copies additional X chromosome. If an egg cell with two additional X chromosomes (XXX) is fertilized by a sperm cell with a chromosome, the resulting child will have syndrome 48,XXXY. Similarly, if a cell with one and chromosome and two additional X chromosomes (XXY) fertilize an ovular cell with a single X chromosome, the resulting child will have syndrome 48, XXXY.

Tests performed in IVAMI: in IVAMI we perform the detection of the alterations associated with syndrome 48,XXXY, 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).