Klinefelter syndrome

Description

47,XXY (or variants/mosaics) - commonest cause of male hypogonadism and infertility
Often under-diagnosed - phenotype can be subtle

Meiotic non-disjunction (maternal or paternal, roughly equal split) -> extra X
Higher X count (48,XXXY etc, rare) -> more severe phenotype ("gene dose" effect)
Extra X -> seminiferous tubule hyalinisation/fibrosis -> primary testicular failure

Karyotype - confirms
Presentation: infertility (azoospermia), gynaecomastia, small firm testes, tall stature with eunuchoid proportions, learning/language delay
Hormones: inc FSH/LH, dec testosterone (primary hypogonadism pattern) - may not manifest biochemically until puberty
Semen analysis - azoospermia in majority

By problem

Hypogonadism - testosterone replacement from puberty onset/when levels fall - improves virilisation, bone density, mood, libido
Fertility - micro-TESE with ICSI - sperm retrieval possible in a proportion even with azoospermia; refer early to fertility specialist, earlier retrieval attempts (younger age) improve yield
Gynaecomastia - reassurance vs surgical reduction if symptomatic/psychosocial impact
Bone health - DEXA surveillance (osteoporosis risk from long-standing hypogonadism)
Developmental/educational support for speech-language delay and learning difficulties

Near-universal infertility without ART, but life expectancy close to normal with testosterone replacement
Testosterone therapy - most improvement in bone/muscle/mood if started early
Untreated hypogonadism -> osteoporosis, metabolic syndrome, reduced quality of life

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