Anosmia predicts hypogonadotropic hypogonadism in CHARGE syndrome.
OBJECTIVE
To test the hypothesis that a smell test could predict the occurrence of hypogonadotropic hypogonadism (HH) in patients with CHARGE syndrome, which is a variable combination of ocular coloboma, heart defects, choanal atresia, retardation of growth/development, genital hypoplasia, and ear anomalies or hearing loss caused by mutations in the CHD7 (chromodomain helicase DNA binding protein 7) gene.


METHODS
We performed endocrine studies and smell testing (University of Pennsylvania Smell Identification Test) in 35 adolescent patients with molecularly confirmed CHARGE syndrome.


RESULTS
Complete data on smell and puberty were available for 15 patients; 11 patients had both anosmia and HH, whereas 4 patients had normosmia/hyposmia and spontaneous puberty. In addition, 7 boys were highly suspected of having HH (they were too young for definite HH diagnosis, but all had cryptorchidism, micropenis, or both) and had anosmia. The type of CHD7 mutation could not predict HH because a father and daughter with the same CHD7 mutation were discordant for HH and anosmia.


CONCLUSIONS
Anosmia and HH were highly correlated in our cohort, and therefore smell testing seems to be an attractive method for predicting the occurrence of HH in patients with CHARGE syndrome. The use of this test could prevent delay of hormonal pubertal induction, resulting in an age-appropriate puberty.
Bergman
Jorieke E H
JE
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Bocca
Gianni
G
Hoefsloot
Lies H
LH
Meiners
Linda C
LC
van Ravenswaaij-Arts
Conny M A
CM
D000293:Adolescent; D000328:Adult; D058747:CHARGE Syndrome; D002648:Child; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D007006:Hypogonadism / Q000150:complications / Q000175:diagnosis*; D008279:Magnetic Resonance Imaging; D008297:Male; D009426:Netherlands; D000857:Olfaction Disorders / Q000175:diagnosis* / Q000209:etiology; D009830:Olfactory Bulb / Q000473:pathology; D011237:Predictive Value of Tests; D011628:Puberty, Delayed / Q000517:prevention & control*