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At a glance

It is a congenital syndrome characterized by the association of hypogonadotropic hypogonadism with anosmia (or hyposmia). It is characterized by failure of puberty. Left untreated, patients with Kallmann Syndrome will almost invariably be infertile. The condition can occur in both males and females, but is more commonly diagnosed in males (4:1).

Synonyms

de Morsier Syndrome II; Hypogonadotropic Hypogonadism 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; Morsier-Gauthier Syndrome.

History

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.

Incidence

1:10,000 males, 1:50,000 females of live births. The incidence in Finland during a determined period of all born individuals was estimated at 1 in 48,000 newborns. There was a clear difference in estimates between boys (1 in 30,000) and girls (1 in 125,000). A precise estimate of prevalence remains unknown as it may be affected amongst differences in different populations.

Genetic inheritance

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. The male-to-female ratio is established at 4:1.

Pathophysiology

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.

Diagnosis

Clinical features, biochemical (low serum levels of androgens and positive response to GnRH stimulation), and MRI/CT imaging (unilateral or bilateral absent olfactory bulbs).

Clinical aspects

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 lip and/or palate 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 Syndrome).

Precautions before anesthesia

Assess cardiac function ...

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