Syndrome 48, XXYY

Symptoms of this syndrome include:

Usually people have 46 chromosomes in each cell. Two of the 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female sexual characteristics. Women usually have two X chromosomes (46, XX), and men have one X chromosome and one Y chromosome (46, XY). Syndrome 48, XXYY occurs due to the presence of an additional copy of both sex chromosomes in each of the cells. Additional copies of the genes on the X chromosome interfere with the sexual development of men, interfering with the normal functioning of the testicles and lowering testosterone levels. Many genes are found only on the X or Y chromosome, but genes in regions known as pseudo-autosomal regions are present on both sex chromosomes. Additional copies of genes from pseudo-autosomal regions of extra X and Y chromosomes contribute to the symptoms of the syndrome; however, specific genes have not been identified ^{[3] [4]} .

The syndrome is not inherited; It usually occurs by chance during the formation of reproductive cells (ovum and sperm). An error in cell division, called non-exclusion, leads to the appearance of a reproductive cell with an abnormal amount of chromosomes. With syndrome 48, XXYY, additional sex chromosomes almost always come from sperm. The mismatch can lead to the sperm acquiring two additional sex chromosomes, as a result of which the sperm will have three sex chromosomes (one X and two Y chromosomes). If this sperm fertilizes a normal egg with one X chromosome, the resulting child will have two X chromosomes and two Y chromosomes in each of the cells in his body.

In a small percentage of cases, syndrome 48, XXYY is the result of non-switching of the sex chromosomes in embryo 46, XY very soon after fertilization. This means that a normal sperm with one Y-chromosome fertilized a normal egg with one X-chromosome, but immediately after fertilization, mating of the sex chromosomes forced the embryo to receive two additional sex chromosomes, as a result of which the embryo has a karyotype 48, XXYY ^[3] .

For diagnosis, a karyotype is checked ^[5] .

Patients usually should be observed by an endocrinologist. In the presence of hypogonadism, testosterone treatment should be considered in all people, regardless of cognitive abilities, due to the positive effect on bone health, muscle tone, fatigue and endurance, as well as with possible benefits for mental health / behavior ^[2] .

Most children with XXYY have some developmental delays and learning difficulties. Therefore, these aspects should be observed: psychology (cognitive and socio-emotional development), speech therapy, occupational therapy and physiotherapy. Consultations should be arranged with developing pediatricians, psychiatrists or neurologists to develop a treatment plan that includes therapy, behavioral interventions, educational support, and psychotropic drugs for behavioral and psychiatric symptoms. General diagnoses, such as learning disabilities, ADHD, autism spectrum disorders, mood swings, tick disorders, and other mental health problems should be examined, examined, and treated. In this group, there are good reactions to standard medication treatments for inattention, impulsivity, anxiety and mood instability, and such treatment can positively affect academic performance, emotional well-being in the long term. Poor coordination of fine motor skills can make writing a slow and time-consuming task, and occupational therapy and a keyboard should be introduced at an early age to facilitate school work and self-help skills. Educational difficulties should be assessed using a full psychological assessment to identify discrepancies between oral and work skills and identify individual academic needs. Language skills often suffer throughout life, and interventions in speech therapy may be required in adulthood, aimed at developing expressive language skills, dyspraxia, and others. Adaptive skills are difficulties requiring community support for almost all people in adulthood ^[2] . Additional treatment recommendations may be required based on the individual strengths and weaknesses of XXYY syndrome ^[6] .

Patients have an almost normal life expectancy, but they require regular medical supervision ^{[3] [7]} .

The first published report of a boy with karyotype 48, XXYY, was published by Sylphest Muldal and Charles Oka in Manchester in 1960 ^[8] . It was described in a 15-year-old boy with mental disorders who had signs of Klinefelter syndrome ; however, the karyotype test showed 48, XXYY. Because of this, syndrome 48, XXYY was initially considered a form of Klinefelter syndrome. Common physical and medical features due to the presence of an additional X chromosome include high growth, development of testosterone deficiency in adolescence and / or adulthood (hypergonadotropic hypogonadism) and infertility. However, recent studies have revealed some important differences in people with karyotypes 48, XXYY compared to 47, XXY ^[5] . The most important differences are due to the influence of additional X and Y chromosomes on the development of the nervous system, which leads to a higher incidence of developmental delays in early childhood, learning disabilities or mental retardation, difficulties with adaptive functioning, nervous development disorders such as ADHD or autistic disorders spectrum and psychological / behavioral problems, including anxiety, depression and impaired mood regulation. In addition, a larger percentage of men with XXYY have additional medical problems, such as cramps, congenital anomalies of the elbow joint (radial synostosis), and tremors compared with men with XXY. XXYY is still considered a variation of Klinefelter’s syndrome by some definitions, mainly because the pathophysiology of testicular dysfunction is no different from 47, XXY, and the most recent studies do not suggest that there should be any differences in the assessment and treatment of testosterone deficiency in 48. XXYY compared to 47, XXY ^[9] . However, the psychological and behavioral symptoms of XXYY syndrome usually require more extensive assessments, interventions, and support compared to 47, XXY because of a more complex involvement in the development of the nervous system. Significant variability is observed between people in the number and severity of medical problems and nervous system development problems associated with XXYY, and some people have mild symptoms, while others suffer in a more significant way ^[2] .