Background: Prader-Willi syndrome (PWS), caused by loss of paternally imprinted genes in the 15q11-13 region, results in hypogonadism which is more severe in males.
Objective: To review the gonadal status of patients seen in a dedicated PWS clinic from 19902013 inclusive so as to establish the clinical patterns and hence to optimise future management.
Method: Retrospective case note review over a 23-year period.
Results: 80 patients (50 males: 30 females) with PWS due to paternal deletion (51), maternal disomy (20), imprinting centre mutation (2), translocation (1) and unknown (6) were seen, median (range) current age 23 (565) years. Females: known age at B2 and menarche was highly variable: range (median) 7.314.8 (11.5) (n=15) and 1118.3 (15.3) years (n=6) with oligo-amenorrhea in all postpubertal patients. Basal/peak LH and FSH at B4-5 were also variable:0.55.3/4.135.4 u/l; and 0.814.1/6.221.3 u/l indicating both central and peripheral hypogonadism. Norethisterone was used to regulate menstrual bleeding in four patients and the combined pill in three girls. Males: Only one boy had normally descended testes. Bilateral/unilateral orchidopexy was recorded in 24/18 patients. Surgery was unsuccessful in nine patients but hCG injections avoided surgery in two boys and brought the testis to the external inguinal ring in five. Age at G2 was 11.715.6 (13.1) with maximum genital stage/testicular volume G3/810 ml (n=8). In boys aged >11 years basal/peak LH&FSH at G1 was 0.53.7/0.523.1 u/l & 0.86.8/0.512.4 u/l (n=8); and at G3 0.77.4/1280.5 & 0.427.7/11.453.9 u/l (n=4). Testosterone replacement was started in 15 subjects aged 13.929.2 years, usually as 100 mg i.m. every 6 weeks.
Conclusion: Hypogonadism is almost constant in PWS, manifesting as pubertal delay with oligoamenorrhea in girls; cryporchidism and pubertal delay with arrest at G3 in boys; and biochemical features of mixed central and peripheral gonadal impairment in both sexes. Preoperative hCG rarely avoids but may facilitate surgery. Boys require testosterone treatment from around 13 years in order to complete puberty. The case for treating postpubertal girls with oestrogen remains uncertain.
01 Oct 2015 - 03 Oct 2015