User:Maria0330/XXXXY syndrome

49,XXXXY syndrome is an extremely rare aneuploidic sex chromosomal abnormality. It occurs in approximately 1 out of 85,000 to 100,000 males. This condition is one the rarest sex chromosome disorders (X and Y variations) and is caused primarily due to changes made to the number of sex chromosomes.  This syndrome is the result of maternal non-disjunction during both meiosis I and II. It was first diagnosed in 1960 and was coined Fraccaro syndrome after the researcher. Below are details with regard to the signs and symptoms of 49, XXXXXY, it's physical anomalies, skeletal anomalies, cognitive, behavioural, neurological, and developmental anomalies, and current information available about potential treatments for the condition.

Signs and symptoms
The symptoms of 49,XXXXY are slightly similar to '''another sex chromosome disorder commonly known as Klinefelter syndrome (KS) or even as 47, XXY. However after looking over more case studies and medical reports with regard to each condition, physicians and researchers have expressed both 47, XXY and 49, XXXXY should be seen and evaluated as distinct and separate conditions as patients present different signs and symptoms overall and with the latter being more severe. This syndrome is also slightly similar to''' 48,XXXY, but they are usually much more severe. Aneuploidy is often fatal, but there is "X-inactivation", where the effect of the additional gene dosage due to the presence of extra X chromosomes is greatly reduced.

Physical Anomalies
Physical anomalies with regard to males diagnosed with 49, XXXXY syndrome include dysmorphic facial features such as microcephaly; where the size of an infant's head is much smaller than normal, hypertelorism; where children have an increased amount of space between specific body parts (for example, too big of a gap between the eyes), and moreover, children diagnosed with this syndrome may also have a broad nasal bridge as compared to other children who do not have the condition.

Case studies have shown that patients diagnosed with 49, XXXXY typically have the following:


 * Arched eyebrows
 * Epicanthic folds
 * Broad nasal bridge/nose
 * Low-set ears
 * Synophrys (the eyebrows connect to the bridge of the nose)
 * Hypoplasia with regard to the corpus collosum (usually mild)
 * Upslanting palpebral fissures

Skeletal Anomalies
Furthermore, skeletal anomalies in males diagnosed with 49, XXXXY include  pes planus; which is when an individual has flat fleet and thus has no arch along the bottom of their foot, hyperextensibility of the fingers, fifth finger clinodactyly; where the fifth digit (the pinky) is curved inward and thus results in a more irregular/wedge shaped phalange instead of the typical straight phalange that is typically seen, genu valgum; when an individuals knees are bent and touching one another even when both legs pointing straightforward, this is also referred to as knock-knee, radioulnar synostosis; where the ulna and radius, two important bones in the forearm are are abnormally connected, decreased muscle ton, and even increase join hyperextensibility; that causes the individuals fingers to extend backwards more than typically seen.

Cognitive, Behavioural, Neurological, & Developmental Anomalies
Much like Down syndrome, the mental effects of 49,XXXXY syndrome vary. Impaired speech and maladaptive behavioral problems are typical. One study looked at males that were diagnosed with 48,XXYY, 48,XXXY and 49,XXXXY. They found that males with 48,XXXY and 49,XXXXY function at a much lower cognitive level than males their age. These males also tend to exhibit more immature behavior for their chronological age; increased aggressive tendencies were also cited in this study.

Furthermore, males diagnosed with 49, XXXXY syndrome tend to be outgoing, friendly, and shy when interacting with others for the most part, but due to their issues with impaired speech, they may have a hard time communicating and verbalizing their thoughts to those around them, thus leading to behavioural issues such as increased irritability, frustration, temper issues, outbursts, and severe tantrums.

'''Males diagnosed with 49, XXXXY syndrome have also exhibited a significant delay in motor skills and key milestones associated with each age. The range in which these delays occur varies greatly, with some infants beginning to sit up between 8-24 months of age; when the typical age an infant starts to sit at is 6 months of age with support and around 8 months without support, standing between 10-30 months of age; when the typical age is between 9-12 months, and finally, children with 49, XXXXY syndrome start to walk between 16-54 months of age; when the typical age is between 9-18 months. The differences between these key milestones further show how significant the delay is with males who have been diagnosed with this condition.'''

Treatment
While there is no treatment to correct the genetic abnormality of this syndrome, there is the potential to treat the symptoms. As a result of infertility, one man from Iran used artificial reproductive methods. An infant in Iran diagnosed with 49,XXXXY syndrome was born with patent ductus arteriosus, which was corrected with surgery, and other complications that were managed with replacement therapy.

With regard to a potential treatment, one form of therapy that has shown a positive correlation between the course of treatment and the language impairment/deficit that males diagnosed with 49, XXXXY suffer from is known as testosterone replacement therapy. Through the use of patches, injections, gels, or pellets, males can improve their low testosterone levels. However, all of the studies looking into this form of treatment have yet to determine the exact effects that testosterone replacement therapy has on speech skills and strength. Further, testosterone replacement has also been linked to improving and enhancing the development of male-related secondary sex characteristics such as increased overall performance, improved fat distribution, and improved libido. '''Though this form of therapy has its benefits, it is important to note that it does not affect fertility or spermatogenesis. This form of therapy also comes with its own set of long-term risks that patients should be made aware of ahead of time.'''