What is Kallmann Syndrome?
Kallmann syndrome is a rare inherited disorder that mostly, but not exclusively, affects men. The major characteristics of Kallmann syndrome, in both men and women, are the failure to experience puberty and the complete or partial loss of the sense of smell. Failure to go through puberty reflects a hormonal imbalance that is caused by a failure of a part of the brain known as the hypothalamus. Patients with Kallmann syndrome show evidence of small genitalia, sterile gonads that cannot produce the sex cells (hypogonadism), and a loss of the sense of smell (anosmia). The impaired production of hormones as well as sperm and egg cells causes delayed puberty, growth and infertility.
There are three forms of Kallmann syndrome. The most common is known as KAL1. This is an X-linked form, which means that the malfunctioning gene is located on the X chromosome. The malfunctioning gene responsible for the next more common form, KAL2, has been traced to a site on chromosome 8 and the genetic inheritance is transmitted as an autosomal dominant trait. The third and most rare form of Kallmann syndrome is KAL3. This appears to be transmitted as an autosomal recessive trait. The site of the malfunctioning gene has not been determined.
A congenital disorder of hypothalamic function and reduced pituitary gonadotropic activity with resulting association of hypogonadism, eunuchoidism and anosmia. Other clinical abnormalities observed include retinitis pigmentosa, colour blindness, midline cranial and intracranial defects, hypertension, obesity, cryptorchidism, osteopenia, mild neurosensory hearing loss, gynaecomastia, diabetes mellitus, cleft lip or palate, and mental retardation. Anosmia is caused by degeneration of the olfactory bulba. Both sexes affected; prevalent in males (3:1). Most cases autosomal dominant, but recessive and X-linked cases are known. Possibility of female carrier.
The syndrome is sometimes considered as three separate entities, named Kallmann syndromes 1, 2, and 3.
As early as in 1856 A Maestre de San Juan described a the autopsy findings in a 40 year old man with absent olfactory lobes, infantile testicles, very small penis and no pubic hair. A few years later an Austrian journal published the findings by the Austrian pathologist Richard Ladislaus Heschl (1824-1881) who made a similar discovery in a 45 year old man who also had small genitalia and very little body or pubic hair.
In 1914, Franz (1873-Weidenreich undertook post mortem studies in 10 persons with anosmia, 3 of whom had hypogonadism, and suggested that these problems might be syndromically associated. Kallmann and his colleagues in 1944 reported three different families in which a majority of the family members had a syndrome, or certain symptoms of a syndrome, consisting of missing puberty (eunuchoidism), lack of the sense of smell (anosmia), and colour blindness. Some of the family members were also mentally retarded. They drew attention to the genetic aetiology of the disorder. In 1954 De Morsier documented 14 affected persons and confirmed that the anosmia was the consequence of agenesis of the olfactory lobes. |
