49, XXXXY Syndrome is a very rare sex chromosome abnormality with an approximate incidence of 1 in 85,000 male births.  Sometimes, 49, XXXXY Syndrome is referred to as a variant of Klinefelter Syndrome.  Klinefelter Syndrome is a sex chromosome abnormality in which boys have an extra X chromosome and therefore have 47, XXY.  Today, most people distinguish Klinefelter Syndrome from 49, XXXXY Syndrome and other sex chromosome abnormalities because the clinical features can be very different.   Basic genetic concepts tells us that typically, there are 46 chromosomes in every cell in our body.  Each chromosome is made up of hundreds of genes, which are the basic units of heredity and determine all of our physical and chemical traits.  Chromosomes and the genes contained in them occur in pairs.  Most individuals have 22 pairs called autosomes and 1 pair called sex chromosomes.  Females generally have two "X" chromosomes while males generally have one "X" and one "Y" chromosome. Sometimes, when egg or sperm cells are being made, these chromosomes do not divide properly.  This is called non-disjunction.  It is believed that 49, XXXXY Syndrome occurs during maternal non-disjunction during both meiosis I and meiosis II.  Typically, and egg has two X chromosomes which must divide in half, so that each egg has one X chromosome.  Once this occurs, a sperm can fertilize the egg and the fetus ends up with 46, XY, which is a normal male chromosomal constitution.  If by chance the X chromosomes do not separate properly and they go on to the next cell division and again do not divide properly, when the sperm fertilizes the egg the fetus can then end up with 4 X chromosomes and 1 Y giving the fetus 49, XXXXY Syndrome.  Aneuploidy above one extra chromosome is usually fatal but because of X-inactivation, which "turns off" all but one X chromosome per cell, the effects of 3 extra chromosomes are reduced.  This error typically occurs by chance and is not due to anything the parents did or did not do before or during the pregnancy. Although 49, XXXXY Syndrome is genetic, it is usually not hereditary, meaning that the chances that another child with 49, XXXXY Syndrome, or any other chromosome abnormality, in the same family are relatively small and are around 1%.  The 1% comes from studies where every family who has ever had any type of chromosome abnormality (ie. Downs, Klinefelter, ect) are all lumped into one group, and about 1% of those already few people have another instance of a chromosome abnormality in their families.  The chance to have a baby with a chromosomal abnormality increases as the mother gets older, of course.   The classic clinical findings reported in people with 49, XXXXY Syndrome are radioulnar synostosis, mental deficiency, and hypogonadism. Other features include severely impaired speech, behavioral problems, short or broad neck, low birth weight, hyperextensible joints, short stature, round face in infancy, coarse features in older age, hypertelorism, epicanthal folds, prognathism, gynecomastia (rare), congenital heart defects (PDA is most common), skeletal anomalies: genu valgus, pes cavus, fifth finger clinodactyly, muscular hypotonia, hypoplastic genitalia, cryptorchidism, pea-size testes, micropenis, and infantile secondary sex characteristics.  All of this is very mild compared to other rare chromosomal abnormalities, and of course, not everyone displays all of these findings.   Because basic genetic evaluation is relatively new, research on 49, XXXXY Syndrome is also somewhat new.  Years ago, the parents of any baby or child thought to have something "wrong" were told to put their child into an institution.  No child, regardless of chromosomal makeup, would be able to thrive in that type of environment.  Unfortunately, a lot of the studies and research have been on the individuals who were institutionalized; therefore, much of the information available on the degree of mental deficiency and overall well being is not completely accurate. Mentally, 49, XXXXY Syndrome people have varying degrees.  One study reported that with each additional "X" chromosome, the persons IQ diminishes by 15 points.  Most people compare it mentally to Downs Syndrome, in that it varies greatly from person to person.  Major milestones like sitting and walking are reached, but may take a bit longer because of muscle tone issues.  If 49, XXXXY Syndrome is present in a newly diagnosed patient, the best way to learn and to get insight is to read about real people living with it.  Contact other families and hear real life experiences.  These are the people that will be able to provide you with an abundance of actual information, and of course, much needed hope.     Source: "49, XXXXY: a distinct phenotype.  Three new cases and review"  by Jennifer Peet, David D Weaver, Gail H Vance Image from: UW Pathology Cytogenetics Gallery