49, XXXXY syndrome

49,XXXXY syndrome can affect many parts of the body. Affected people typically have delayed growth (often seen in utero, before birth).^[1] Some have short stature and a deficit of growth hormones.^[1] There may be varying degrees of learning difficulty and intellectual disability which can be severe; some report that this worsens with age.^[1][3][4] Behavioral problems can also arise.^[1]

There is usually severe hypogonadism with an abnormally small penis (micropenis), small testes, and/or undescended testes (cryptorchidism).^[1] Most have distinctive facial features which may include a large, flat nose with an up-turned tip; wide-set eyes (hypertelorism); epicanthal folds; protrusion of the lower jaw (prognathism); folded ears; and/or a short neck.^[1][3] Other abnormalities may include:^[1][3]

• skeletal abnormalities and joint laxity
• congenital heart defects
• other endocrine disorders (affecting the hormones)
• abnormalities in the brain (cerebral defects) such as underdevelopment of the corpus callosum (the pathway connecting the 2 hemispheres of the brain)
• renal defects such as renal hypoplasia (small kidneys)
• eye problems such as strabismus and severe nearsightedness (myopia)

Although people with 49,XXXXY syndrome are sometimes referred to as having a variant of Klinefelter syndrome, the features of these are generally distinct and 49,XXXXY syndrome is more severe.^[3]

You can read more about the features of 49,XXXXY syndrome in a fact sheet provided by Unique. The information in this fact sheet comes from both the medical literature and reports of some members of Unique who took part in a survey in 2004.

49,XXXXY syndrome occurs by chance due to a random error in cell division (called nondisjunction) in the egg cells of the mother.^[1][2] During normal egg formation, chromosomes separate and a single X chromosome ends up in each egg cell. If chromosomes don't separate correctly during cell division, one egg cell ultimately can retain all of the X chromosomes that would normally be placed into 4 separate egg cells during cell division. If an egg cell containing four X chromosomes is fertilized by a normal male sperm (with one Y chromosome), the resulting fertilized egg cell will be affected. 

The underlying reason for random errors in cell division is not known. However, there is nothing a person can do, or not do, before or during pregnancy to cause 49,XXXXY syndrome to occur.

The specific features of 49,XXXXY syndrome are thought result from increased "doses" of genes from the extra X chromosomes.^[5]

There is no cure for 49,XXXXY syndrome. Treatment depends on the symptoms present in each person and is often managed by a team of various specialists. Specialists involved in the care of an affected person may include heart doctors (cardiologists), orthopedists, physiotherapists, speech therapists, eye doctors (ophthalmologists), neurologists, and endocrinologists. While life expectancy is thought to be normal in the absence of major complications, affected people will need regular medical visits.^[1]