Prof. Dr.S.RAMASAMY,Dr. A.Prakash, PG,

A 27 year old male, Mr.Vinoth, coming from TP chathram, manual labourer by ocupation, with

c/o sparse facial hair growth

HOPISparse facial hair growthDecreased axillary, pubic hair growthh/o reduced testicular development +h/o breast enlargement +h/o feminine voice +h/o learning difficulties +

• No h/o penile deformity• No h/o difficulty in erection/ejaculation• No history s/o autoimmune condition such as SLE/RA/Sjogrens• No h/o respiratory tract infection• No h/o arthritis/bony deformity• No h/o taurodontism• No h/o abdominal pain/distension• No h/o palpitation/dyspnoea• No h/o skin pigmentation• No h/o syncope/seizure disorders• No h/o chronic drug intake• No h/o visual disturbances

• Past history• Operated for gynaecomastia b/l- 4 yrs

back• No h/o HTN/DM/TB/BA/Seizure disorder• Personal history• Unmarried• Education upto 8th standard, because of

learning difficulties, discontinued his studies

• Not an alcoholic/smoker

Family historyNo h/o similar illness in the familyNo h/o any chromosomal disorder in the

familyTreatment historyOperated for gynaecomastia -4 yrs backTaking Rx for the presenting complaints

for past 1 year

Conscious oriented afebrileNo

pallor/cyanosis/clubbing/icterus/PE/GLAb/l gynaecomastia +, TRANSVERSE

SURGERY SCAR BELOW AREOLA B/LNo facial hair growthNo syndactyly/polydactylyHydration adequateVitals: BP-110/80, PR-76,

CVS- S1 S2 +, no murmurRS- NVBS +, no added soundsP/A soft, no organomegaly, Examination of genetalia-SPARSE PUBIC HAIRTestes- 2×1.5CM;small for age (Normal

4-7 cm)Penis- 3cm, no deformities

Provisional diagnosisChromosomal disorder ? Klinefelter syndrome

? Klinefelter variant

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INVESTIGATION

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Endocrinologist’s opinion obtainedChromosomal anomaly/?klinefelter

syndromeAdvised semen analysis, serum FSH,

Serum testosterone, karyotyping, USG testes & biopsy

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Cardiologist’s opinion obtainedECG-WNLECHO-NORMAL & NO EVIDENCE OF

CHD

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TFT –WNLECG-NSR/WNL

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Semen analysisVolume: 1ml (Normal>2ml)pH: 7.5 (Normal: 7.2-7.8)Concentration: 7×10 ^6/ml (>20)Motility: 50% (>50%)Morphology: 40% normal morphology

(>30%)WBC: <1×10 ^6 (n)

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DIAGNOSISKLINEFELTER SYNDROME-47XXY

KARYOTYPE

Klinefelter syndrome• MC sex aneuploidy in males• It is a disorder in which male infants born with an

extra X chromosome• Incidence- 1/500 – 1/1000 newborn males• 1% among the MR, 3% among the infertile males, 5-

10% among oligospermia & azospermia• Chromosomal aberration mostly from meiotic

nondysjunctions of X chromosome during parental gametogenesis

• The extra X chromosome maternally in origin in 54%, paternal in origin in 46% (Nelson)

• In adult men, the prevalence was only 40/100000, i.e., only 1 in 4 of adult males with klinefelter was diagnosed

• MC chromosomal pattern is 47 XXY (80%)• Mosaic patterns 46XY/47XXY 46XY/48XXYY 45X/46XY/47XXY 46XX/47XXY• Variant 48XXXY 49XXXYY 50XXXXYY 47XXY/48XXXY 47XXY/49XXXXY 48XXYY• Advanced maternal age slightly increases the risk for XXY

chromosome

Clinical features• The condition should be considered in all boys with

MR & in children with psychosocial learning or school adjustment problems

• Children may be anxious, immature, excessively shy, aggressive, may engaged in antisocial acts

• Verbal I.Q.s being somewhat decreased• By late adolescent, learning disbilities usually

language based• In high resolution MRI shows a reduction in left

temporal lobe grey matter volume• Tall, slim, underweight, long legs, testes tend to be

small for age• Cryptorchidism or hypospadiasis may occur in few

patients

• Adult:• Gynaecomastia, sparse facial hair, small testes

(spermatogenic arrest, sertoli cells predominance)• Azoospermia, infertility common• Increased death usually due to DM, epilepsy, peripheral &

intestinal vascular insufficiency, pulmonary embolism & renal disease

• In variants, when the number of X chromosome exceed to the clinical manifestation including MR, impairment of virilizations are more severe

• XXYY is the MC variant, 49 XXXXY hs the most severe manifestation like prenatal fetus had intrauterine growth retardation, edema

Diagnostic procedures• Before birth- amniocentesis, CVS karyotypes• At adult- karyotyping, semen count, serum estradiol level, serum

FSH level, serum LH, serum testosterone• Most males with this condition go through the life undiagnosed• The testes growth normal in the early in puberty, but by mid-

puberty the testicular growth stops, Gonadotropis become elevated, it leads testosterone levels are slightly low

• In this condition inhibin B normal in early puberty, decrease in late puberty, low in adult

• Elevated level of estradiol resulting in a high estradiol-testosterone ratio leads to development of gynaecomastia in puberty

• Long androgen receptor polyglutamine (CAG) repeat length is associated with the more severe phenotype manifestation

• Testicular biopsy- before puberty only reveal deficiency or absence of germinal cells

• After puberty reveal seminiferous tubular hyalinization & adenomatous clumping of leydig cells are established

• Expectation the syndrome increases the risk of ADHD, autoimmune condition ,breast cancer, psychiatric illness, learning disabilities despite normal I.Q., lung disease, osteoporosis, taurodontism is very common in klinefelter syndrome

treatment• Replacement therapy with long acting testosterone

depends on age of patient, should begins at 11-12 years of age, the enanthate ester may be used in a starting dose of 25-50mg i.m. Every 3-4 weeks, with 50 mg increment every 6-9 months until a maintenance dose of adult (200-250mg every 3-4 weeks )is achieved

• Testosterone patches or gel may be substituted for the injection

• Testosterone therapy can help grow body hair, improve appearance of muscles, improve concentration, improve mood and self esteem, increase energy & sex drive, increase strength

THANK YOU

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