Congenital syndrome characterized by the association
of hypogonadotropic hypogonadism with anosmia (or hyposmia).
de Morsier Syndrome II; Hypogonadotropic Hypogonadism and
Anosmia Syndrome; Kallmann-de Morsier Syndrome; Maestre-Kallmann-de Morsier
Syndrome; Maestre de San Juan-Kallmann Syndrome; Maestre de San
Juan-Kallmann-de Morsier Syndrome; Olfactogenital Dysplasia;
Genetic disorder first described in 1856 by the Spanish histologist
Aureliano Maestre de San Juan (1828-1890). The German psychiatrist Franz Josef Kallmann in
1944 pointed out the genetic background of the disease, while the Swiss pathologist
Georges de Morsier published a case series in 1954.
1:10,000 males, 1:50,000 females of live births.
X-linked recessive, also present in autosomal
recessive and autosomal dominant forms; locus on X chromosome at position
22.3 (Xp 22.3). In the X-linked form, there is a mutation in gene KALIG-1,
which encodes for a protein with homology to neural cell-adhesive molecule
(N-CAM); this form can be linked to X-linked ichthyosis, mental retardation,
chondrodysplasia punctata, and short stature. Male-to-female ratio is 5:1
Interference with the migration of endogenous
gonadotropin-releasing hormone (GnRH)-secreting cells arising from the nasal
placode (precursor of the nose) to the hypothalamus during fetal life
resulting in agenesis of the olfactory lobes and GnRH deficiency.
Clinical features, biochemical (low serum levels of
androgens and positive response to GnRH stimulation), and MRI/CT imaging
(unilateral or bilateral absent olfactory bulbs).
Highly variable, but characterized by GnRH
deficiency with hypogonadotropic hypogonadism, delayed incomplete or absent puberty, short
stature, and smelling deficiencies. Neurosensory hearing loss and mild
mental retardation have been reported, but the majority of these patients
have normal intelligence. Choanal atresia and cleft palate and/or lip
are other common features. Renal anomalies include unilateral renal agenesis
and cryptorchidism in males. Infertility, erectile dysfunction, and decreased libido are
common in untreated patients. Most patients have normal lifespan. Kallmann syndrome is
occasionally associated with congenital heart diseases (atrial and ventricular septal
defects, transposition of the great arteries, Ebstein anomaly, aortic arch anomalies, but
also atrioventricular block, bundle branch blocks, and even Wolff-Parkinson-White
Assess cardiac function and rule out any
anomalies and obtain further examinations (ECG, echocardiography) if required. Evaluate
renal function (creatinine, urea). Examine for any indicators of difficult airway
management. Sedative premedication may be helpful in patients with mild developmental
Choanal atresia may account for
respiratory distress. Difficult airway management may be encountered in patients with
cleft lip and palate. Child may be uncooperative because of anxiety
and mild mental retardation. Presence of congenital heart disease may require
prophylactic antibiotics (endocarditis) and invasive hemodynamic monitoring.
Delayed puberty secondary to idiopathic
hypogonadotropic hypogonadism, which is a diagnosis of exclusion, whereas
anosmia and/or associated abnormalities are typical of Kallmann syndrome.
Hardelin JP: Kallmann syndrome: Towards molecular pathogenesis. Mol Cell Endocrinol
MacColl G, Bouloux P, Quinton R: Kallmann syndrome: Adhesion, afferents, and
anosmia. Neuron 34:675, ...