49, XXXXY syndrome is a rare chromosome abnormality that only affects males and is caused by three extra copies of the X chromosome. Symptoms of the condition include mild to severe learning difficulty, speech issues, abnormal physical and sexual development which lead to shorter than average height and small genitals, low muscle tone (hypotonia), narrow shoulders and chest, and subtle facial features. Body abnormalities can include a twisted foot at birth (clubfoot), abnormal bones in the forearms that make it difficult to do certain movements, bent fifth fingers, and loose (bendy) joints. Kidney, heart, and, in rare cases, brain abnormalities (defects) may also be present at birth. Some boys with this condition are at an increased risk for respiratory tract infections.
Even though 49, XXXXY syndrome is considered a genetic condition, it is not inherited. It is a random (sporadic) chromosome abnormality that occurs as a result of abnormal chromosome separation in an egg cell from the mother. Normally, a mother’s egg cells divide during a process known as meiosis. During this process, a cell that contains 46 chromosomes (including two X chromosomes) separates into cells that contain 23 chromosomes (each with one X chromosome). However, in rare cases, the X chromosomes do not separate during this process and create egg cells that have four X chromosomes (instead of one X chromosome). When the egg cell that has four X chromosomes is fertilized by the sperm cell that has one Y chromosome, it creates an embryo with four Xs and one Y (49, XXXXY). The condition is usually suspected in a boy with abnormal facial features and learning issues, but the diagnosis is confirmed with a chromosome analysis blood test (karyotype). There is no cure for this condition, but therapies can help with learning difficulties. Additional information is available through support groups.