1. Copyright 2014 American Medical Association. All rights reserved.
Anosmia in a 9-Year-Old Boy
Karan R. Chhabra, AB; Nicole A. Sherry, MD; Donald G. Keamy Jr, MD, MPH
A 9-year-old boy presented with anosmia of unknown duration.
His parents thought it had been present since birth, noting that
he had lacked interest in food for many years. The patient had no
history of sinusitis, chronic congestion, snoring, or mouth breath-
ing. His medical history was significant for recurrent otitis media
(tympanostomy tubes had been placed at age 4 years), high-
frequency hearing loss, and cryptorchidism (orchiopexy at age 18
months). He was also seeing an endocrinologist for short stature.
His endocrinology records showed that his size was appropriate
for his family (his mother was 157 cm, his father 165 cm) and that
his rates of growth and weight gain were normal. He was prepu-
bertal, with no family history of anosmia or delayed puberty. On a
smell identification test performed in the office, he placed in the
first percentile.1
He failed the 12-in alcohol smell test. Anterior rhi-
noscopy revealed septal deviation but no other abnormalities.
Flexible fiber-optic examination of the nose revealed no masses,
polyps, or cysts, with a minimal adenoid pad. A magnetic reso-
nance image (MRI) of the nasal cavity obtained under anesthesia
is shown in Figure 1.
What is your diagnosis?
Figure 1. A magnetic resonance image of the nasal cavity.
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2. Copyright 2014 American Medical Association. All rights reserved.
Diagnosis
Kallmann syndrome (KS)
Discussion
The MRI in Figure 2 shows an absent right olfactory bulb, minimal
left olfactory bulb, and blunted olfactory sulci bilaterally, key radio-
logic manifestations of KS.
Kallmannsyndromeisararediseasethatcombineshypogonado-
tropic hypogonadism with anosmia. The differential diagnosis of
anosmiainchildrenincludesviralinfection,cranialtrauma,andneo-
plasticactivity.Althoughadetailedmedicalhistoryandphysicalex-
aminationareimportant,computedtomographyorMRIisrequired
toruleoutneoplasms,unsuspectedfractures,andparanasalsinusitis.2
The diagnostic characteristic of KS is a low level of serum go-
nadotropinsandgonadalsteroidsinconjunctionwithanosmiaorhy-
posmia. Early diagnosis in young children can be challenging. First,
theyoftencannotexplaintheirsensorydeficit,andparentsmaybe
skeptical of their complaints. Second, hypogonadism and hypogo-
nadotropism may not be apparent without clinical suspicion and
laboratorystudies.3
Finally,notallpatientsarebothanosmicandhy-
pogonadic, and neither characteristic is always fully penetrant.4
Establishinganosmiaisalsonottrivial,becausechildrenmaylie
to please their parents or to attract attention. Anosmics may also
be able to sense certain irritants, such as ammonia, which are
“smelled”throughthetrigeminalnerve.5
Thesimplestolfactiontest
is to hold a fresh alcohol wipe 30 cm from the child’s nose. How-
ever,theUniversityofPennsylvaniaSmellIdentificationTest,which
combinesscratch-and-sniffodorsandmultiple-choicequestions,is
often more informative.2
Total anosmics may score slightly higher
than predicted by chance (because of the trigeminal pathway), but
a patient scoring significantly lower than predicted by chance may
not be answering truthfully.1,2
TheunusualsetofsymptomsinKSisattributabletothecommon
embryonicoriginofolfactoryandGnRH(gonadotropin-releasinghor-
mone)secretingneurons,intheolfactoryplacode.GnRH-secreting
neurons follow the olfactory tracts to their destination in the hypo-
thalamus;defectsinthispathwayleadtoKS.Kallmannsyndromemay
beaccompaniedbyabnormalsexualdevelopment,neuromuscular
abnormalities(particularlysynkinesia),sensorineuraldeafness,uni-
lateral renal agenesis, and/or cleft lip and palate.6
TheincidenceofKSisestimatedat1:8000-10 000inmalesand
1:40000-50000infemales.3
Itsgeneticsarecomplex;knownmuta-
tions explain less than 30% of cases. Some responsible genes are
X-linked.Mutationsmayalsobeacquireddenovoratherthaninherited.3
Treatment consists of family education and hormone therapy.
Children with anosmia rarely sense spoiled food, smoke, and other
signsofdanger.Thus,familiesshouldtakeextracautionwithfoodex-
pirationdatesandinvestinexplosivegasandsmokedetectors.7
Sex
steroid replacement will promote secondary sexual characteristics
inbothmalesandfemales,butpulsatileGnRHorgonadotropinsare
necessaryfornormalfertility.6
Withlifelongtreatment,patientscan
maintain secondary sexual characteristics and bone density.
This patient’s family, concerned with his limited diet and short
stature,hadseenanendocrinologist,dietician,andgastroenterolo-
gist.Kallmannsyndromewaslikelyinvolvedinbothhisdietandstat-
ure as well as his cryptorchidism.8
But until he presented with an-
osmia, KS was not suspected. With his early KS diagnosis, he may
not need exogenous growth hormone to increase his final height.
Because he will likely not enter puberty without administration of
testosterone,hewillprobablyhavealongerperiodofgrowth.Thus,
althoughanosmiaisincurable,improvedendocrinetreatmentisan
important benefit of diagnosing KS in a timely manner.
ARTICLE INFORMATION
Author Affiliations: Rutgers Robert Wood Johnson
Medical School, Piscataway, New Jersey (Chhabra);
Massachusetts General Hospital, Boston (Sherry);
Massachusetts Eye and Ear Infirmary, Boston
(Keamy).
Corresponding Author: Karan R. Chhabra, AB,
Rutgers Robert Wood Johnson Medical School, 675
Hoes Ln W, Piscataway, NJ 08854 (krchhabra
@gmail.com).
Section Editor: C. Douglas Phillips, MD.
Published Online: September 25, 2014.
doi:10.1001/jamaoto.2014.2081.
Conflict of Interest Disclosures: None reported.
Additional Contributions: Mary Elizabeth
Cunnane, MD (Massachusetts Eye and Ear
Infirmary), provided and interpreted the
radiographs in this case. She was not compensated
for her contributions.
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hypogonadism (Kallmann syndrome). Am J Med.
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5. Hummel T, Livermore A. Intranasal
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Crowley WF. Kallmann syndrome. In: Pagon RA,
Adam MP, Bird TD, Dolan CR, Fong CT, Stephens K,
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8. Ferris AM, Schlitzer JL, Schierberl MJ, et al.
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149-156.
Figure 2. Magnetic resonance image showing an absent right olfactory bulb,
minimal left olfactory bulb (white arrowhead), and blunted olfactory sulci
bilaterally (yellow arrowhead).
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