A Genetic Twist to Tales about George Washington, Napoleon Bonaparte, and Abraham Lincoln

Dr. Harry Klinefelter and his coworkers at the Massachusetts General Hospital in Boston published in 1942, a report about nine male patients who had some peculiar characteristics such as enlarged breasts, sparse facial and body hair, and small testes.  Further examinations also proved that these patients have an innate inability to produce sperm.  This condition was later called Klinefelter syndrome. Researches done to study this male group from that time on until about the late 1950s led to the discovery of an extra sex of chromosomes in the male sex cells, which was later referred to as XXY, which is unusual compared to the normal male arrangement, which is XY.

The most commom chromosomal disorder associated with male hygogonadism and infertility, Klinefelter syndrome is classically defined by a 47, XXy karyotype with variants demonstrating additional X and Y chromosomes. Characteristically, Klinefelter syndrome is recognized by hypogonadism, which is the presence of small testes, and azoospermia or oligospermia, which is the absence of sperm cells or producing very low sperm supply. It is also characterized by gynecomastia at late puberty, which is the development of abnormally large breasts on men, as well as psychosocial problems, hyalinization and fibrosis of the seminiferous tubules, and elevated urinary gonadotropins.

The extra X or Y chromosome to a male karyotype results in variable physical and cognitive abnormalities. Generally, the extent of these abnormalities, including mental retardation, is related directly to the number of extra X chromosomes.  As the number of X chromosomes increases, somatic and cognitive development are more likely to be affected.  Skeletal and cardiovascular abnormalities can become increasingly severe.  Gonadal development is particularly susceptible to each additional X chromosome, resulting in seminiferous tubule dysgenesis and infertility as well as hypoplastic and malformed genitalia in polysomy X males.

Because of these characteristics, Klinefelter syndrome is observed only among males. Because of low testosterone levels, boys with Klinefelter syndrome may have sparse pubic, facial, and body hair, underdeveloped muscles.  They may be taller than other males in their family and have long legs, narrow shoulders, and wide hips. The smaller-than-expected testicles, are generally infertile, and cannot father children without special surgical techniques.

Klinefelter syndrome is seen in 1 in 1,000 total live births, or 1 in 500 male live births. Experts describe the XXY boys puberty as normal, i.e., without any delay of physical maturity.  But as puberty progresses, they fail to keep pace with other males. In chromosomally normal teenaged boys, the testes gradually increase in size, from an initial volume of about 2 ml, to about 15 ml.  In XXY males, while the penis is usually of normal size, the testes remain at 2 ml, and cannot produce sufficient quantities of the male hormone testosterone.  As a result, many XXY adolescents, although taller than average, may not be as strong as other teenaged boys, and may lack facial or body hair. As they enter puberty, many boys will undergo slight breast enlargement. For most teenaged males, this condition, known as gynecomastia, tends to disappear in a short time.  About one-third of XXY boys develop enlarged breasts in early adolescence slightly more than do chromosomally normal boys. Furthermore, in XXY boys, this condition may be permanent.  However, only about 10 percent of XXY males have breast enlargement great enough to require surgery.

There are generally are no signs of Klinefelter syndrome until puberty.  At this time, boys with Klinefelter syndrome often do not have the increase in testosterone levels that normally occurs.

Up to this time, no one knows what puts a couple at risk for conceiving an XXY child.  It has been thought that advanced maternal age increases such risk, but only slightly.  Furthermore, recent studies conducted by NICHD grantee Terry Hassold, a geneticist at Case Western Reserve University in Cleveland, OH, show that half the time, the extra chromosome comes from the father. Dr. Hassold explained that cells destined to become sperm or eggs undergo a process known as meiosis. In this process, the 46 chromosomes in the cell separate, ultimately producing two new cells having 23 chromosomes each. Before meiosis is completed, however, chromosomes pair with their  corresponding chromosomes and exchange bits of genetic material.  In women, X chromosomes pair; in men, the X and Y chromosome pair.  After the exchange, the chromosomes separate, and meiosis continues.

In some cases, the Xs or the X chromosome and Y chromosome fail to pair and fail to exchange genetic material.  Occasionally, this results in their moving independently to the same cell, producing either an egg with two Xs, or a sperm having both an X and a Y chromosome.  When a sperm having both an X and a Y chromosome fertilizes an egg having a single X chromosome, or a normal Y- bearing sperm fertilizes an egg having two X chromosomes, an XXY male is conceived.

Maternal nondystjunction, which is 75% meiosis I error, is considered the most popular sources of Klinefelter sundrome cases.  in most cases, maternal age is very high. The other cases are due to paternal nondusjunction, with the most common form as 47,XXY, mosaicism in the 46,XY/47,XXY form.  Other variants include 48,XXYY, 48,XXXY, 49,XXXYY, and in rarest cases, 49,XXXXY.

Klinefelter syndrome usually does not cause mental retardation, but affected males test slightly lower than their brothers and sisters on IQ testing. They also may have problems talking and hearing.  Most of them though, have normal intelligence. Mental capacity has been found to diminish with the additional X chromosomes.  The intelligence quotient (IQ) is reduced by approximately 15 points for each supernumerary X chromosome, but conclusions about reduced mental capacity must be drawn cautiously.  All major areas of development, including expressive and receptive language and coordination, are affected by extra X chromosome material.

Although some exceptions may be considered, XXY boys are usually well behaved in the classroom.  Most are typically shy, quiet, and eager to please the teacher.  But when faced with material they find difficult, they tend to withdraw into quiet daydreaming.  Teachers sometimes fail to realize they have a language problem, and dismiss them as lazy, saying they could do the work if they would only try.  Many become so quiet that teachers forget they're even in the room.  As a result, they fall farther and farther behind, and eventually may be held back a grade.

XXY males usually have difficulty with expressive language the ability to put thoughts, ideas, and emotions into words.  In contrast, their faculty for receptive language-understanding what is said-is close to normal. In addition to academic help, XXY boys, like other language disabled children, may need help with social skills.  Language is essential not only for learning the school curriculum, but also for building social relationships.  By talking and listening, children make friends in the process, sharing information, attitudes, and beliefs.  Through language, they also learn how to behave, not just in the schoolroom, but also on the playground. 

Throughout childhood-perhaps, even for the rest of their lives, XXY boys retain the same temperament and disposition they first displayed as infants and toddlers.  As a group, they tend to be shy, somewhat passive, and unlikely to take a leadership role.  Although they do make friends with other children, they tend to have only a few friends at a time.  Researchers also describe them as cooperative and eager to please.

The National Society of Turner Contact Groups reported that boys with Klinefelter syndrome manage well in school within the normal range, but with a tendency to certain learning difficulties, especially during the first years at school can be observed. This can, however, be remedied by a conscientious school staff and environment.  Learning difficulties are most pronounced during the first years at school, though they may not be present in nearly all Klinefelter boys.

Learning difficulties such as a short memory span can be overcome by careful analysis and appropriate measures.  It is of great importance for both parents and educators to know this and to act accordingly.  If there are problems in relation to speech development it is also important that speech therapy is given.

If conditions at home are good, stable and stimulating, and if there have been good conditions in the day institution, where the Klinefelter boy has been, learning problems rarely have any consequences.

As reported by the MeritCare Health Systems, males with Klinefelter syndrome appear to have reduced abilities in specific areas, which includes language development, which usually accompanies delayed or slowly development of speech skills and poor verbal skills, critical thinking skills, problem solving, and ability to plan, multi-tasking, impulse control, and response time.

Furthermore, boys are described to have emotional problems that range from being shy and immature to being overly anxious or aggressive.  They may also have poor social skills, which may cause problems for them in school and in

other social situations.  They are at risk for developing psychiatric disorders, such as anxiety, depression, and drug and alcohol abuse

Experts believe that Klinefelter Syndrome doesn't affect intelligence, since  learning disabilities do not mean the child is limited intellectually.  Wolfram E. Nolten, an associate professor of medicine in the division of endocrinology, diabetes and metabolism at the University of Wisconsin in Madison and a board member for The American Association for Klinefelter Syndrome Information and Support, was quoted as saying that kids with Klinefelter Syndrome have perfectly normal IQs.  Furthermore, not every child with Klinefelter Syndrome will have every characteristic.  Some typical traits related to learning and social functions include talking later than other children, trouble with coordination and agility, low muscle tone which affects coordination, walking, jumping and hopping, language-based learning problems, shyness especially when speech is atypical, depression and anxiety.

          Dr. Nathaniel Robin, Medical Geneticist at the University of Alabama and expert in the ethical issues of genetic testing and research, explored why historic figures, whose physical characteristics included infertility, tall stature, and gynecomastia, are suspected of having Klinefelter syndrome.  He had discussed some issue like George Washington’s infertility, Napoleon’s growing breasts, Abraham Lincoln’s being tall and skinny, etc., which may be another twist to Klinefelter syndrome’s hitting some popular political figures of our society.