What Are the Major Symptoms of Klinefelter Syndrome?

Klinefelter syndrome is caused by a genetic defect in a supernumerary X chromosome in a male.

Klinefelter syndrome refers to a group of chromosomal disorders in which there is an extra X chromosome. Klinefelter syndrome is the most common chromosomal cause of primary hypogonadism and infertility in males. The condition only affects males.

In neonates and prepubescent boys (only the most severe cases are identified before puberty) symptoms include:

• Micropenis (less than 1.9 cm for neonates) 
• Curved fingers (clinodactyly)
• Urethra not located on the tip of the penis (hypospadias)
• Undescended testicles (cryptorchidism)
• Behavioral problems
• Language delay
• Learning disabilities
• Increased distance between the eyes (hypertelorism)

Other symptoms of Klinefelter syndrome include:

• Small testes (micro-orchidism)
• Low sperm count/lack of sperm in semen (oligospermia/azoospermia)
• Breast tissue development (gynecomastia) in late puberty
• Tall height with long arms and legs 
• Delayed or incomplete development in puberty
• Sparse facial, body, and sexual hair 
• Erectile dysfunction 
• Osteoporosis 
• Breast cancer 
• Speech and language deficits (especially in expressive language) 
• Learning disabilities (lower verbal IQ than performance IQ scores) 
• Poor self-esteem 
  • Anxiety
  • Depression
• Behavioral problems
  • Substance abuse

Early identification is helpful in treating and managing Klinefelter syndrome. 

Testosterone replacement therapy is a mainstay of treatment.

Other treatments may include:

• Speech and reading therapy for those with learning disabilities
• Tutoring for academic difficulties
• Counseling for psychosocial and behavioral problems
• Physical therapy for boys with low muscle tone (hypotonia) or delayed gross motor skills that may affect muscle tone, balance, and coordination
• Occupational therapy for boys with motor coordination disorder (dyspraxia)
• Artificial reproductive technologies for infertility 
• Surgery (reduction mammoplasty) for men with cosmetically bothersome breast tissue growth (gynecomastia)

Complications of Klinefelter syndrome include:

• Increased risk of extra-testicular germ cell tumors 
• Increased risk of breast cancer
• Increased risk of certain other cancers including acute leukemia, Hodgkin and non-Hodgkin lymphomas, chronic myelogenous leukemia
• Psychological and psychiatric complications in men with lower-than-average intelligence, hypogonadism, or impotence
  • Higher risk for autism and schizotypal traits
  • Deficiencies in verbal abilities 
  • Deficiencies in visuospatial abilities  
• Decreased bone density/osteoporosis
• Deep vein thrombosis (DVT)
• Endocrine complications 
  • Diabetes mellitus
  • Low thyroid (hypothyroidism)
  • Empty sella syndrome
  • Hypoparathyroidism
  • Precocious puberty in association with human chorionic gonadotropin (hCG)–producing germ cell tumors
  • Prepubertal boys (aged 4-12 years) are at elevated risk for truncal obesity, insulin resistance, and childhood metabolic syndrome. 
• Autoimmune diseases, such as systemic lupus erythematosus, Sjögren syndrome, and rheumatoid arthritis are more common
• Enlarged prostate (benign prostatic hyperplasia, or BPH)
• Cerebrovascular diseases 
  • Aortic valvular disease 
  • Berry aneurysm rupture 
  • Enhanced platelet aggregation
  • Thrombotic disease
  • Hypercoagulability 
  • Varicose veins and leg ulcers 

Life expectancy for patients with Klinefelter syndrome is reduced by five to six years. 

Patients diagnosed at a younger age seem to have a shorter lifespan, possibly because diagnosis at an earlier age is associated with a more severe phenotype.