| Abstract | 46,XY gonadna disgeneza (GD) je jedan od poremećaja diferencijacije spola u kojeg se javlja nesklad između kromosomskog, fenotipskog i anatomskog spola. Dijeli se, ovisno o fenotipu i kariotipu, na kompletnu, parcijalnu ili miješanu 45,X/46,XY. Kod kompletnog 46,XY GD-a bolesnici su ženskog fenotipa sa trakastim gonadama i normalno razvijenim strukturama porijekla Müllerovih cijevi. Klinička slika parcijalnog 46,XY GD-a i miješanog 45,X/46,XY GD-a je vrlo varijabilna, od muškog fenotipa preko dvosmislenog do ženskog. Osobe 45,X/46,XY GD-om mogu imati i fenotipske karakteristike Turnerovog sindroma. Uzrok nastanka kompletnog i parcijalnog 46, XY GD-a su patogene varijante u genima koji sudjeluju u determinaciji i diferencijaciji spola poput SRY, NR5A1, SOX9, WT1, WNT4, MAP3K1 itd. Miješani 45,X/46,XY GD posljedica je nerazdvajanja sestrinskih kromatida tijekom mitoze u fazi zigote. Svi bolesnici neovisno o tipu bolesti imaju povećan rizik za razvoj gonadoblastoma.
Na 46, XY GD se može posumnjati odmah pri rođenju ukoliko novorođenče ima dvosmisleno spolovilo, a osobito u osoba s parcijalnim i miješanim oblicima. U osoba kompletnim 46, XY GD-om na bolest se posumnja najčešće tek u doba adolescencije, i to zbog izostanka pubertetskog razvoja. Liječenje je hormonsko nadomjesno i kirurško.
Rano prepoznavanje bolesti, postavljanje što preciznije dijagnoze kao i multidisciplinarni te individualizirani pristup poboljšavaju dugoročne ishode i kvalitetu života oboljelih osoba. |
| Abstract (english) | 46,XY gonadal dysgenesis (GD) one of the disorders of sex development in which there is difference between chromosomal, phenotypic and anatomic gender. Its subtypes, depending on phenotype and karyotype include complete, partial and mixed 45,X/46,XY (GD). In complete 46.XY GD patients have female phenotype, streak gonads and presence of normal Müllerian structures. Clinical presentation of partial and mixed 45,X/46,XY GD is very variable, from normal male phenotype, ambiguous genitalia to normal female phenotype. People with 45,X/46,XY GD can have phenotypic features of Turner syndrome. Etiology of complete and partial GD are mutations in genes which are involved in sex determination and differentiation such as SRY, NR5A1, SOX9, WT1, WNT4, MAP3K1 etc. Mixed 45,X/46,XY GD is a result of chromatid nondisjunction during mitosis in zygote phase. All patients, regardless of type of GD have increased risk of developing gonadoblastoma.
Diagnosis of 46,XY GD, especially partial and mixed type, can be established at birth when the child has ambiguous genitalia. Patients with complete form of 46,XY GD are usually diagnosed in adolescence, due to absence of pubertal development. Treatment for GD include hormonal replacement therapy and surgical procedures.
Early recognition, prompt and correct diagnosis as well as multidisciplinary and individual approach increase quality of life of these patients and improve long-term outcomes. |
