Transcript Klinefelter Syndrome

Tall Stature with
Arrested Puberty
M. Hashemipour
Professor of Pediatric Endocrinology
Isfahan University of Medical Sciences
Case 1
15.5 year-old boy
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Referred for gynaecomastia.
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Tall stature, does not want to grow taller.
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What do you ask him?
Case 1
o
o
o
o
Tall since early childhood, but more excessively at 12
years
Pubic hair started at age 12
sense of smell
School performance
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Forgetful, Poor academic performance
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Family history
The only child.
 Mother: one miscarriage, healthy, height 145 cm
 Father: type 2 diabetes, height 163 cm
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What's important in Physical examination?
145
163
What's important in Physical examination?
Auxology
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Height 179.1 cm;
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Arm span 186cm
Weight 87.0 kg
BMI 27.2
voice did not change
 Gynaecomastia noted at the age of 12 years old
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Pubertal exam
Pubertal Staging
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Pubertal exam
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Testes 4/4 mls
Pubic hair TS 4
Eunuchoid body
habitus
Gynaecomastia
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Abdominal striae
BP 12/7
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what's Eunuchoid body habitués
Arm span _ Height
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The arm span is the distance between the tips of
the middle fingers when the arms are raised to a
horizontal position .
Arm span - Height
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1 – 7 yr
8 – 12 yr
> 12 yr : Boys
Girls
17
_3
0
+1
+4
Upper to lower segment
The upper segment to lower segment ratio
 Birth
: 1.7
 3 years: 1.33
 5 years : 1.17
 10 years : 1.0
Upper to lower segment
 pre-puberty
 During
ratio
puberty
 Adult men
 Adult woman
≥1
≤1
o.92
0.95
Eunuchoid proportions
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Lower segment 2-5cm >upper segment
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Arm span – Height> + 5 cm
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What's your investigation
Bone age
Bone age: 14 years at
chronological age 15
years 6 months
Investigations
LH: 35.6 mIU/ml (prepubertal <1.0)
FSH 51.8 mIU/ml (prepubertal <1.0)
Testosterone 4.5 nmol/L (pubertal 8.4-28.7)
FBS, lipid profile and liver enzymes: normal
Chromosomal Study
Chromosomal study
47 XXY
Father: 46 XY
Mother: 46 XX
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what is the most likely diagnosis?
Diagnosis
 Klinefelter
syndrome with
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Gynaecomastia
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Obesity
Treatment
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Testosterone 100mg 4-weekly, and to achieve
250mg 4-weekly by 6 months.
Obesity:
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Weight reduction: healthy diet, behavioural changes,
exercise
Gynaecomastia
Monitor for regression after starting testosterone
and weight reduction
 May need surgery if fails to regress
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Discussions
Klinefelter Syndrome (1942)
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Prevalence 1 in 500-1000 males
Increased incidence with advanced maternal age
Classical KS: 47 XXY (80-90%)
Variants:
46 XY/47 XXY mosaicism
 48 XXXY; 48 XXYY
 Phenotypic males with 46 XX, Y to X translocation
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Klinefelter Syndrome
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Mutation causes:
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Hyalinization and fibrosis of seminiferous tubules
and aggregation of Leydig cells
Azoospermia
 Variable testosterone deficiency
 Elevated gonadotropin
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Klinefelter Syndrome
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Clinical features: diagnosis rarely made before puberty
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Height: above average, disproportionately long legs
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Small penile size
Low IQ
learning disabilities
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Features of Klinefelter’s
syndrome
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Taller than average
height
Reduced libido
Reduced facial and body
hair
Gynaecomastia
Small testes
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Fatigue
Depression
Osteoporosis
Fat accumulation
(abdomen, hips)
Poor erections
Infertility
Handelsman DJ, Zajac JD. Med J Aust 2004; 180: 529–35.
Klinefelter Syndrome
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At risk of:
Low bone mineral density
 Type 2 DM
 Varicose veins, venous thrombosis, pulmonary
embolism
 Early tooth decay
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Klinefelter Syndrome
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At risk of
Infertility
 Breast carcinoma
 Extra-gonadal germ cell mediastinal
 Increased incidence of autoimmune disease: SLE,
RA and Sjogren synd.
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Klinefelter Syndrome
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Treatment:
Androgen replacement
 Surgery for severe gynaecomastia.
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