Klinefelter sydrome clinical features

KLINEFELTER
SYNDROME

CLINCAL FEATURES

Clinical Features

• The physical features that the patients present will depend on
the developmental stage and the severity of the syndrome

• KS should be suspected in neonatal boys with micropenis,
hypospadias, cryptorchidism, teenage boys with late puberty
or men with small testes / infertility / having signs of androgen
deficiency

• The main pathological cause of their phenotype is due to
hypogonadism (reduced activity of gonads to produce sex
hormone) as a result of progressive destruction and fibrosis of
testicular tissues (both spermatogenic and steroidogenic)

• Mosaic individuals tend to have milder phenotype and often
present at later age

• Because of the variability of presentation features, patients
usually gets diagnosed late, with the mean age of 30yo

Neonates & prepubertal Pubertal boys
boys
• Absent or incomplete
• The most severe forms pubertal development
usually gets diagnosed
early • Small testis
• Scant facial and pubic hair
• Micropenis • Gynaecomastia (due to low
• Clinodactyly
testosterone : estrogen ratio)
• Hypospadias • Taller than expected
• Cryptorchidism • Legs length grow out of
• Hypertelorism
proportion to arms length
• Learning disability
• Behavioral abnormalities
• Language delay

Adulthood

• Less severe phenotypes, usually gets diagnosed during
adulthood

• Presents with infertility (azoospermia)
• Gynaecomastia, sexual dysfunction, osteoporosis
• Small, firm testes – due to progressive degeneration and

fibrosis of testicular tissue
• Men with mosaic KS may have normal sized testes

Klinefelter syndrome

Others

• Dentofacial abnormalities - taurodontism (an
enlargement of the pulp of molars on dental
radiography; might be associated with increased
risk of caries), mandibular prognathism and
absence of permanent teeth

• Cardiovascular - increased relative risk of metabolic
syndrome, ischemic heart disease, mitral valve
prolapse, lower extremity varicose veins and
venous stasis ulcers, and deep venous thrombosis
and pulmonary embolism

• Pulmonary - Chronic obstructive pulmonary
disease and pneumonia are more likely to be
diagnosed

• Musculoskeletal - Increased lifetime risk of
osteoporotic fracture, osteoarthritis, persistently
decreased muscle mass and weakness (even after
testosterone therapy) that is at least partially due
to congenital and peripubertal hypogonadism.

• Neurological - Increased prevalence of essential
tremor and a Parkinson-like syndrome with tremor in
men with classic Klinefelter syndrome. More than 25
percent of patients with Klinefelter syndrome may
have tremor

• Autoimmune disease - Such as rheumatoid arthritis,
systemic lupus erythematosus, and autoimmune
endocrinopathies (eg, Hashimoto's thyroiditis and
type 1 diabetes mellitus) are relatively more
common

• Cancer –

• Risk of breast cancer is up 50-fold higher than
normal male population, but the absolute
lifetime risk of breast cancer in these men is
<1 percent. Men with Klinefelter syndrome
account for 4 percent of all cases of male
breast cancer

• Extragonadal germ cell cancer and non-Hodgkin lymphoma also
appear to occur at higher frequency, but the absolute risk is small

• The lifetime risk of prostate cancer appears to be lower than the
general adult male population

References

• Zitzmann et. al. European Academy of Andrology Guidelines on Klinefelter Syndrome. Andrology.
2021;9:145–167

• Patel et. al. Klinefelter syndrome.Accessed at https://www.docplexus.com/posts/klinefelter-
syndrome-a-rare-genetic-disorder on 10th July 2022

• Kondo et. al. A case of a rare variant of Klinefelter syndrome: 47,XY,i(X)(q10). Andrologia.
2018;e13024

• Kanakis et. al. Klinefelter syndrome: More than hypogonadism. Metabolism. 2018 Sep;86:135-144.

• Mitral valve prolapse. Accessed at https://middlesexhealth.org/learning-center/diseases-and-
conditions/mitral-valve-disease on 12th July 2022

• Rheumatoid arthritis. A.D.A.M.S Images. Accessed at https://www.adamimages.com/ on 12th July
2022

• Matsumoto et. al. Up to Date: Clinical features, diagnosis, and management of Klinefelter
syndrome. Accessed at https://www-uptodate-com.ezaccess.library.uitm.edu.my/contents/clinical-
features-diagnosis-and-management-of-klinefelter-
syndrome?search=klinefelter&source=search_result&selectedTitle=1~58&usage_type=default&dis
play_rank=1 on 10th July 2022

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