The American Association for Klinefelter Syndrome Information and Support
AAKSIS is a national volunteer association with the mission of education, support, research, and understanding of 47,XXY and its variants, collectively known as Klinefelter syndrome. AAKSIS is guided by Roberta Rappaport and has been dedicated to bringing you accurate and current information about Klinefelter Syndrome. Beginning in 2014, AAKSIS became part of AXYS and provided substantial support to the design of a completely new AXYS website. In 2017 AAKSIS was a major sponsor of the AXYS Family Conference in Colorado.
Klinefelter Syndrome, 47,XXY, the most common of the sex chromosome variations, is said to occur in 1 out of 500 males. Statistics suggest that there are thousands of 47,XXY individuals in the United States alone. Many remain undiagnosed. Current and accurate information about 47,XXY required by those confronted with a new diagnosis is often unavailable.
AAKSIS has always striven to raise awareness among medical professionals and the general public. Its professional advisors provided educational programs aimed at providing the latest information and research to its community and anyone interested in learning more about Klinefelter Syndrome.
AXYS honors AAKSIS, its board of directors and its advisors for their profound accomplishments in raising awareness of Klinefelter syndrome and improving the lives of those who are impacted by the diagnosis!
Please meet the former AAKSIS board of directors
Please meet the AAKSIS advisory board
AAKSIS Founder and President, Roberta Rappaport can be reached at 888 466-5747
About Klinefelter Syndrome
by Dr. Wolfram E. Nolten
Klinefelter Syndrome (KS) affects 1 in 500 male conceptions and is therefore the most common sex chromosome abnormality. It results in small testes, testosterone deficiency, infertility and often in swelling of glandular breast tissue (gynecomastia). The first report in 9 patients, by HF Klinefelter Jr, EC Reifenstein Jr and F Albright in 1942, was followed by the discovery of an extra X chromosome as the cause of KS by PA Jacobs and JA Strong in 1959. More than two thirds of KS patients have the 47, XXY karyotype, few present with more than 2 X chromosomes or with mosaicism, having a normal XY and another abnormal XXY cell line. Testicular biopsy shows hyalinized and fibrotic seminiferous tubules, with few, if any, areas of sperm production. Seminiferous tubules normally comprise 85% of the testicular volume, and degenerative changes, such as fibrosis and hyalinization of the seminiferous tubules are the cause of testicular atrophy, which is invariably present in KS.
The chromosomal abnormality in KS is caused by an error in the division process in the production of gametes, where sperm or ovum contain an extra X chromosome, in addition to the normal X or Y chromosome. Advanced maternal age may be associated with these division errors in KS.
Whereas a smear of the buccal mucosal membranes can show sex chromatin (Barr bodies), representing the extra X chromosome in KS men, a chromosome analysis, performed in peripheral blood cells will usually confirm the diagnosis of KS, define the number of X chromosomes and provide information about the presence of mosaicism. In the untreated adult KS patient, testosterone levels are usually low or below normal, with elevated LH.
The diagnosis of KS is frequently made by prenatal genetic testing. In infancy the KS boy may present with a small penis, hypospadia or undescended testes. At school-age the child may show behavioral problems or learning disabilities. The adolescent may have tall stature, excessive growth of the lower extremities and delayed puberty, eunuchoidal features and small testes usually remaining at a volume of 2-3 mL. Testosterone production reaches a plateau after age 14 years and may never reach the midnormal adult range, in spite of high levels of LH stimulation. Adult KS patients have decreased bone mineral density, which could be caused by testosterone deficiency. Many adult KS men are first diagnosed during an infertility evaluation, when testicular atrophy and absence of sperm in the ejaculate are noticed. KS patients have a high incidence of learning disabilities with decreased verbal IQ, but usually normal intellectual performance. Language skills can be impaired, patients may be aggressive, being not inclined to participate in social activities and having a tendency to depression.
KS can be complicated by mild adult-onset diabetes mellitus with insulin resistance, by hypothyroidism, by varicose veins of the lower extremities which can cause venous ulcers, by thinning of the surface of the teeth (taurodontism), which can cause early decay, by breast cancer that may develop in middle age, by leukemia and Hodgkin and non-Hodgkin lymphoma, and in the young by gonadal or extragonadal germinal cell tumors, frequently located in the mediastinum. Cerebrovascular accidents are more common in KS than in men with a normal 46, XY karyotype.
It is desirable to establish the diagnosis of KS as early as possible. This will direct the observation of parents to learning disabilities and behavioral abnormalities, which require remedial action. Attention should be paid to the possibility of complications, and screening tests should be ordered. In adolescence testosterone replacement should be initiated, as soon as gonadotropin levels increase above normal. Testosterone doses must be advanced over years with yearly increments, imitating the increase in testosterone production that occurs during normal puberty. Testosterone not only will advance virilization and support development of adequate bone mineralization, it also can improve fatigue, muscle strength, academic performance and further social adjustment.
In earlier years KS was thought to be invariably associated with antisocial behavior and mental retardation. This impression was prompted by institutionalized patients, whose findings served for earlier reports. Clinical experience with a wider segment of the population and decades of follow-up of KS men provide much more positive information. Early diagnosis, observation and remedial action for emotional and behavioral abnormalities and timely treatment with testosterone can modulate the clinical course of KS and permit patients to live a full life as contributing members of our society.
Editor’s Note: Dr. Nolten has given us a broad overview of Klinefelter Syndrome. In the preceding article, he referred to medical, educational, and psychological problems that may be related to this disorder. Dr. Nolten was a founding member of AAKSIS and was also on its Board of Directors until the time of his death in January 2009.
What is 47,XXY/Klinefelter Syndrome?
International Klinefelter Syndrome Resources
Denmark – klinefelter.dk
Germany – klinefelter.de
Japan – tokyo-med.ac.jp/genet/ks/indexj.html
Netherlands – klinefelter.nl
Norway – klinefelter.no
UK – ksa-uk.co.uk and klinefelter.org.uk
Intersex Society of North America
Lesbian, Gay, Bisexual, and Transgender Resources
International Foundation for Gender Education
Educational, Medical, and Advocacy Groups
American Association of Clinical Endocrinologists
1000 Riverside Avenue, Suite205
Jacksonville, FL 32204
Telephone: (904) 353-7878
Home Page: www.aace.com
Christopher Seymour, M.B.A., Executive Director
A professional medical organization of physicians with special education, training, and interest in the practice of clinical endocrinology. Provides information and education to endocrine patients so that they can have access to the best endocrine care possible. Does not include medical advice and diagnosis.
“The First Messenger” (bimonthly newsletter)
Endocrine Practice (bimonthly professional clinical journal)
Clinical Guidelines for various endocrine conditions, and a comprehensive membership directory that supplies addresses, phone numbers, specializations, clinical interests, and board certifications of members.
American Foundation of Thyroid Patients
18534 N. Lyford
Katy, TX 77449
Telephone: (281) 855-6608
Home Page: thyroidfoundation.cfsites.org
Kelly Hale, President
A national, non-profit organization for the awareness, education, and support of thyroid patients,their family members, healthcare providers, and interested parties. Support/Interest groups forming around America, low-cost public thyroid disease screenings, educational information/seminars, thyroid physician referrals.
Quarterly education newsletter/latest findings in thyroid disease, self-help information.
American Speech-Language-Hearing Association (ASHA)
10801 Rockville Pike
Rockville, Maryland 20852
Home page: www.asha.org/
The mission of the American Speech-Language-Hearing Association is to promote the interests of and provide the highest quality services for professionals in audiology,speech-language pathology, and speech and hearing science, and to advocate for people with communication disabilities.
American Society for Bone and Mineral Research
1200 19th Street NW., Suite300
Washington, DC 20036
Telephone: (202) 857-1161
Fax: (202) 223-4579
Home page: www.asbmr.org/
Julia A. Janko, Executive Director
A professional organization of physicians, dentists, veterinarians, and other doctors interested in research and bone and mineral diseases. Supports clinical and basic research studies and encourages and mentors young scientists in the field of bone and mineral metabolism. There is no patient referral system except to osteoporosis or Paget’s disease organizations.
Journal of Bone and Mineral Research(monthly); membership roster (biennially); newsletter (quarterly).
American Society of Human Genetics
9650 Rockville Pike
Bethesda, MD 20814
Telephone: (301) 571-1825
Home Page: www.ashg.org
Elaine Strass, Executive Director
A professional society of physicians, researchers, genetic counselors, and others interested inhuman genetics. Strives to inform health professionals, legislators, health policy makers, and the general public about all aspects of human genetics.
American Journal of Human Genetics(monthly)
Membership Directory (biennially)
Supplement to Journal (annually)
Guide to Human Genetics Training Programs in North America.
American Thyroid Association
Montefiore Medical Center
111 East 210th Street, Room 311
Bronx, NY 10467
Telephone: (718) 882-6047
Fax: (718) 882-6085
Home Page: www.thyroid.org
Diane Miller, Administrator
A professional organization of physicians and scientists dedicated to scientific research on the thyroid. The association refers the public to member physicians in their geographic area on request.
Newsletter (quarterly); information pamphlets.
Health Information for Adults
NIH Osteoporosis and Related Bone Disease National Resource Center
Access Australia – Australia’s National Infertility Network
ASRM – American Society for Reproductive Medicine
Weill Cornell Medicine – Center for Male Reproductive Medicine and Microsurgery
The International Council on Infertility Information Dissemination, Inc.
Resolve – The National Infertility Association
Society for the Study of Male Reproduction