Eziologia e patogenesi

In realtà, nella definizione attuale, la Sindrome di Klinefelter (SK) descrive un gruppo di patologie cromosomiche caratterizzate dalla presenza di almeno un extra-cromosoma X rispetto al cariotipo maschile normale 46,XY. In tal senso il cariotipo più frequente è 47,XXY, ma possiamo avere anche 48,XXXY, 49,XXXXY e 49,XXXYY oltre a mosaicismi 46,XY/47,XXY, 47,XXY/48,XXXY o più complessi. Il mosaicismo è un’alterazione genetica che consiste nella presenza, in uno stesso soggetto di cellule con corredo genetico diverso le une dalle altre. Questo aspetto è importante perché normalmente le manifestazioni cliniche della sindrome sono tanto più gravi quanto maggiore è il numero dei cromosomi X sopranumerari. I dati della letteratura riportano un decremento medio del quoziente intellettivo (QI) di circa 15 punti per ogni X “in più” (Linden et al, 1995).

La causa dell’aneuploidia è un difetto nella separazione dei cromosomi in una fase della riproduzione cellulare definita meiosi. La meiosi consiste nella formazione di quattro cellule con “mezzo” corredo cromosomico (detto aploide) a partire da un’unica cellula eucariotica, vale a dire con corredo cromosomico diploide. La meiosi è caratteristica dei gameti: lo spermatozoo e la cellula uovo (ovocita). Una mancata separazione dei cromosomi che si sono replicati nella meiosi, che avvenga durante la formazione dei gameti nella madre o nel padre, determina rispettivamente circa il 50% dei casi di cariotipo classico della Sindrome di Klinefelter: 47,XXY (Iitsuka et al, 2001; Bojesen et al, 2007); l'età avanzata della madre e probabilmente del padre sarebbero correlate con l’aumento del rischio. Nei mosaicismi la non-disgiunzione si realizza durante le prime divisioni delle cellule dell’embrione ed avviene in circa il 10% dei casi.

In questa sezione troverete le seguenti schede relative alla Sindrome di Klinefelter

• Aspetti endocrini della Sindrome di Klinefelter
• Clinica della Sindrome di Klinefelter
• Terapia della Sindrome di Klinefelter

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