Editing Disorders of Sexual Differentiation (section)

==== Klinefelter syndrome ====
* '''<span style="color:#ff0000">Karyotype: characterized by 1 Y chromosome and ≥ 2 X chromosomes</span>'''
** '''<span style="color:#ff0000">Most common karyotype will be 47,XXY'''
* '''Epidemiology'''
** Incidence: 1 in 600 live-born males
*** '''<span style="color:#ff0000">Most common major abnormality of sexual differentiation'''
* '''<span style="color:#ff0000">Clinical characteristics (7):</span>'''
*# '''<span style="color:#ff0000">Primary hypogonadism</span>'''
*#* '''Leydig cells are present, but testosterone production is abnormally low, with elevated gonadotropins and estradiol'''
*#* '''The decreased androgen production may impair normal secondary sexual development'''.
*#** '''Muscle development may be poor, and the fat distribution is more female than male'''
*#* '''Facial hair is sparse'''
*#'''<span style="color:#ff0000">Small, firm testes</span>'''
*#* Seminiferous tubules undergo replacement with hyaline after pubertal development
*#* '''Predisposed to developing extra-gonadal (e.g. mediastinal) germ cell tumours as well as non-germ cell tumours (Leydig and Sertoli cell tumors [not gonadoblastoma])'''
*#** Routine surveillance scrotal ultrasonography has been advocated for post-pubertal patients
*# '''<span style="color:#ff0000">Gynecomastia</span>'''
*#* Common development during puberty
*#* Result of an increased ratio of estradiol to testosterone
*#* Can be quite marked
*#* '''8x the risk for development of breast carcinoma, requiring lifelong surveillance after puberty'''
*# '''<span style="color:#ff0000">Infertility</span>'''
*#* '''<span style="color:#ff0000">Most commonly identified genetic cause of male infertility</span>'''
*#*'''<span style="color:#ff0000">Vast majority are azoospermic</span>'''
*#** '''Presence of sperm suggests 46,XY/47,XXY mosaicism'''
*#* '''<span style="color:#ff0000">Fertility is possible with the use of testicular sperm extraction (TESE)</span>'''
*#** Some advocate combining intracytoplasmic sperm injection (ICSI) with pre-implantation diagnosis, given the lower (54%) rate of normal embryos from Klinefelter syndrome patients
*# '''Autoimmune disorders'''
*# '''Above average height''', mainly because of the disproportionate length of their legs
*# '''Neurophysiologic and cognitive deficits'''
*#* Decreased verbal skills, frontal executive function and cognitive skills
* '''Management'''
** '''Exogenous testosterone to treat signs and symptoms associated with low testosterone'''
** Reduction mammoplasty, if necessary
** '''Surveillance for testicular tumor and breast carcinoma'''