Klinefelter Syndrome

Question 1

What is the genetic abnormality in Klinefelter syndrome?

Answer 1

79% XXY
20% 46XY/47XXY mosaicism (2 cell lines)
1% 48XXXY; 48XXYY, 49XXXXY, etc.

Question 2

What is the inheritance pattern of Klinefelter syndrome?

Answer 2

sporadic

Question 3

What is the recurrence risk of Klinefelter syndrome?

Answer 3

<1%

Question 4

What are the associated medical findings with Klinefelter syndrome?

Answer 4

1. Malignancy
   a) Male breast cancer 20 fold over XY men
   b) ALL; Hodgkins and non-Hodgkins lymphoma
   c) hCG secreting tumors (extragonadal germ cell tumors)
2. Hypercoagulable state (DVT and PE risk in adults)
3. Relatively tall; long arm span > Height
4. Endocrine
   a) Infertility; azospermia; XY/XXY mosaic males occasionally fertile (25%
   risk of XXY sons).
   b) Small penis, crytporchidism or small testes
   c) Gynecomastia; skin striae
   d) Delayed puberty; low testosterone and increased LH and FSH by ages 12
   to 14 yr
5. Decreased energy, endurance, poor coordination
6. Autoimmune disorders (SLE, RA, Thyroid, NIDDM)
7. Scoliosis; osteoporosis
8. Taurodontism (thin tooth surface; enlarged pulp chamber); dental decay

Question 5

What are the developmental outcomes in Klinefelter syndrome?

Answer 5

1. Delayed Expressive Language
   a) Dysrpaxia – poor phonemic development, motor imitation, decreased
   vocalizations
2. Incidence of MR not increased
3. Lower verbal IQ for normal performance IQ
4. Specific learning disabilities, Dyslexia, memory problems, difficulty with written language
5. Behavioral: shy or withdrawn, low maturity for age, some with low self-esteem, anxiety, neuroses, depression
6. ADHD

Question 6

What is the DDx Klinefelter syndrome?

Answer 6

1. Hearing loss, autism
2. Kallman Syndrome (deficient olfaction) and other causes of hypogonadotropic
   hypogonadism
3. Prepubertally, the milder spectrum of Fragile X Syndrome

Question 7

What are the recommendations for Klinefelter syndrome?

Answer 7

1. Reassure regarding gender identity
2. Peds Endocrinologist for testosterone replacement IM or patch
   a) Begin age 11-12 yr.
   b) More masculine pubertal development; muscle mass
   c) Improves bone mineral density
   d) Improves self-esteem, mood and behavior
3. Plastic surgery available for gynecomastia
4. Monitor for male breast cancer
5. School accommodations/Early Intervention for language problems
6. Behavioral support

Question 8

What are the major clinical manifestations for Klinefelter?

Answer 8

1. Small testicular size
2. Sparse body hair
3. Gynecomastia
4. Eunuchoid body habitus
5. Infertility