XYY SYNDROME: SYMPTOMS, CAUSES, TREATMENT - GEOGRAFÍA - 2024

The XYY syndrome is a genetic disease that is one of the most common chromosomal abnormalities in males. At a clinical level, this pathology is characterized by an exaggerated increase in physical growth (macrocephaly, high height and weight), generalized delay in psychomotor development and difficulties in the acquisition of language skills.

XYY syndrome occurs as a consequence of a genetic abnormality that results in an increase in the number of sex chromosomes. That is, it consists of the presence of a Y chromosome added.

Karyotype of a man with XYY syndrome

Regarding the diagnosis, although the signs in most cases are not usually clinically evident, it is usually based on the identification of alterations related to learning and behavior. Furthermore, a genetic study is essential to confirm its presence.

On the other hand, at present there is no cure for this type of disorder, however, all interventions are mainly directed towards special education, physical therapy or the treatment of medical complications.

History

This pathology was initially described by Jacobs in 1960, who was primarily interested in the behavioral traits of those affected, defined by the propensity to violence and crime.

After the discovery of DNA and the development of study methods and tools, during the 60s and 70s, the exploration of this pathology focused mainly on the identification of its most common phenotypic characteristics.

In particular, most of the studies focused on the analysis of the possible association between sex chromosomal abnormalities and the presence of developmental disorders or socially deviant behaviors.

Historically, the XYY syndrome has been associated with an aggressive and violent behavioral phenotype. Furthermore, in many cases, this disease was erroneously referred to as a "super-male" disorder, since the extra copy of the male sex chromosome was associated with the development of more pronounced physical characteristics and behaviors in this sex.

However, at present, this pathology is defined at a clinical level by the increase in physical development and the presence of psychomotor disorders or other learning problems.

Characteristics of XYY syndrome

The XYY syndrome is a pathology of genetic origin that is characterized by the presence of an extra copy of the sex chromosome Y in males. In this sense, human beings have a total of 46 chromosomes organized in pairs, that is, 23 pairs. Within these, one of the pairs determines the biological sex of the individual.

Specifically, the pair of sex chromosomes that define an embryo as female is made up of two X chromosomes, while the pair of sex chromosomes that differentiate an embryo as male is made up of an X and a Y chromosome.

Thus, the division and combination of all genetic information, in addition to sex, will determine all cognitive and physical characteristics.

Extra sex chromosome

However, during prenatal development the incidence of various pathological factors or the presence of abnormal mechanisms can lead to a failure in chromosomal organization, leading to the presence of an extra sex chromosome. In this case, in XYY syndrome, the chromosomal alteration affects the number of Y sex chromosomes, generating an additional one.

Is it frequent?

Chromosome-related abnormalities and alterations are one of the most frequent of all those that affect this genetic structure.

In this sense, the XYY syndrome constitutes one of the most common chromosomal alterations in the male population.

On the other hand, different epidemiological analyzes have determined that the XYY syndrome has an approximate incidence of 1 case per 1,000 newborns.

In the case of the United States, this pathology can affect 5-10 newborn children daily.

Finally, as for the sociodemographic characteristics associated with the frequency of this pathology, as we have indicated, it is a disease that exclusively affects males.

Furthermore, no other types of patterns related to geographic location and origin or belonging to particular ethnic and racial groups have been identified.

Signs and symptoms

Genetic abnormalities associated with XYY syndrome will produce a series of clinical signs and symptoms. However, in a large part of those affected this condition does not present in a relevant way, so it can remain undiagnosed for life.

Therefore, although the XYY chromosome configuration does not usually cause unusual or significantly pathological physical characteristics, it is possible to identify some signs and symptoms frequently among affected individuals:

Physical development

One of the fundamental features of the XYY syndrome is the course of physical development, being more accentuated or exaggerated than expected for the sex and biological age of the affected person.

From early childhood it is possible to identify a significant increase in the speed of growth and physical development. Thus, both height during childhood and final adult height are usually above the average of the general population, around 7 cm above it.

Normally, in adulthood, those affected usually exceed 180 cm in height. In addition, physical development usually includes other types of characteristics such as a significant increase in the general corporal configuration or the development of general macrocephaly.

Macrocephaly is defined as a type of neurological disorder in which it is possible to identify an abnormal or exaggerated increase in the total size of the head. Thus, in individuals with XYY syndrome, a head circumference greater than expected for their biological age and sex may develop.

Although macrocephaly does not usually cause significant medical complications, in most cases it can be associated with the development of seizures, corticospinal dysfunctions or developmental disorders, among other types of alterations.

Musculoskeletal disorders

Abnormalities related to bone and muscle structure are fundamentally associated with the accelerated speed of physical growth. One of the most significant physical findings in XYY syndrome is the identification of marked muscular hypotonia.

Muscle hypotonia is defined by the presence of abnormally decreased muscle tone. Visually, this alteration can materialize in an exaggerated flaccidity of the extremities or joints.

In general, muscular hypotonia will cause other types of complications such as the inability to coordinate muscle and motor, poor control of the limbs or head, etc.

Neurological disorders

In addition to the anomalies described above, it is possible that other types of alterations related to the neurological sphere and the presence of pathologies associated with the individual's nervous system may appear. In this sense, the presence of tremors is another characteristic symptom of the XYY syndrome.

Tremor can be defined as the presence of a rhythmic involuntary muscle movement. It usually affects the hands and arms as a priority, although the head or voice may also be affected.

Although this clinical finding is not a serious symptom, it can cause secondary complications associated with the acquisition of motor skills or the execution of activities of daily living.

On the other hand, in many affected by XYY syndrome, it is also possible to identify the presence of motor tics. These consist of the development of sudden uncontrollable movements in specific muscle groups. Some of the most common are related to blinking, facial expressions, or abnormal arm or leg movements.

In addition, the genetic genotype can cause alterations related to the nervous system, giving rise to anomalies associated with the cognitive sphere that we will describe below.

Delayed psychomotor development

In a generalized way, the motor development of affected individuals is usually deficient from the first stages of life.

Motor alterations, such as muscular hypotonia or the presence of tremors, will significantly hinder the acquisition of various basic skills, such as the ability to walk or adopt postures.

Learning problems

At the cognitive level, another characteristic feature of people with XYY syndrome is the presence of learning-related disorders.

In this sphere, the most common anomalies are associated with language, that is, a marked difficulty can be observed in acquiring skills related to communication and mastery of a language.

Normally, more than 50% of those affected have a learning disorder. In this sense, dyslexia is one of the most frequent.

Behavioral and emotional disturbances

In most of the cases reported in the clinical literature, behavioral abnormalities related to autism spectrum disorders have been described.

In addition, in terms of specific characteristics, they frequently present an explosive temperament, impulsive and defiant behaviors, hyperactivity or antisocial behavior.

Causes

This syndrome is the product of a genetic alteration related to the chromosomal structure.

The clinical features of XYY syndrome are caused by the presence of an extra Y chromosome. As a consequence, the affected person has a total of 47 chromosomes instead of 46.

Despite the fact that this usually affects all cells of the body in a generalized way, many affected only present this genetic abnormality in some of them, this phenomenon being known as mosaicism.

At the specific level, all the individual genes that may be involved in this pathology are not yet known.

Diagnosis

The characteristic signs and symptoms of XYY syndrome are usually evident in childhood, since learning and other problems related to the cognitive sphere reach an evident level of complexity.

However, some patients may have an asymptomatic clinical status, so the diagnosis is never made.

In the usual cases, the diagnostic suspicion begins with the identification of physical signs (exaggerated growth, macrocephaly, etc.) and cognitive alterations (acquisition of motor skills, acquisition of communication, etc.).

Once a good part of the characteristics have been identified, it is necessary to carry out various laboratory tests:

• Hormonal test: hormonal analyzes focus on evaluating the levels of sex hormones in the body. Normally, it is about identifying the volume of testosterone in the blood, whose abnormal levels may indicate the presence of an alteration.
• Chromosome analysis: It is essential to perform a genetic study to identify the presence of additional chromosomes.

Treatment

The medical interventions used in XYY syndrome are primarily supportive. Currently there is no cure for this disease, therefore, treatment is oriented towards working with learning difficulties or psychomotor retardation.

In several cases where behavioral problems are of significant magnitude, cognitive-behavioral psychological intervention is likely to be required.

References

1. Alonso, G., Fernández-García, D., & Muñoz-Torres, M. (2005). XYY male with azoosperimia. Endocrinol, 134-8.
2. CGD. (2016). XYY Syndrome. Clinical Genetics Department. Obtained from the Clinical Genetics Department.
3. del Río, M., Puigvert, A., & Pomerol, J. (2007). 47, XYY syndrome and infertility: about a case. Rev Int Androl., 312-5.
4. Genetics Home Reference. (2016). 47, XYY syndrome. Obtained from Genetics Home Reference.
5. Healthline. (2016). What Is XYY Syndrome? Obtained from Healthline.
6. Nguyen-Minh, S., Büherer, C., & Kaindl, A. (2014). Is microcephaly a so-far unrecognized feature of XYY syndrome? Meta Gene 2, 160-163.
7. NIH. (2016). 47, XYY syndrome. Obtained from Genetic DNA Rare Diseases Infromation Center.
8. NORD. (2016). XYY Syndrome. Obtained from National Organization for Rare Disorders.
9. Re, L., & Briskhoff, J. (2015). The 47, XYY syndrome, 50 years of certainties and doubts: A systematic review. Agression and Violent Behavior, 9-17.
10. Villa Milla, A., & Martínez-Frías, M. (2000). Cytogenetic diagnosis with result 47, XXY. Propositus.