Kallmann syndrome is a medical condition characterized by idiopathic hypogonadotropic hypogonadism with anosmia. The scientific research into this condition has improved our understanding of it, and helped to improve the diagnostic and treatment recommendations for clinical practice.
The discovery of the kisspeptin protein, and identification of its role as a key regulator of gonadotropin-releasing hormone (GnRH) secretion, has led to advancements in the understanding of human reproduction and the involvement of neuroendocrine regulation.
There has also been significant research into the genetic inheritance of the disease, and individual susceptibility to develop the condition.
Kisspeptin Protein Research
Kisspeptin is a protein linked to Kallmann syndrome. It is involved in the regulation and release of GnRH from the hypothalamus. GnRH then acts upon the anterior pituitary gland to stimulate the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Kisspeptin and the associated receptor ligand, GDR54, play an important role in the initiation and regulation of puberty. For this reason, much of the research into the pathophysiology of Kallmann syndrome has focused on this protein and how it affects the onset of puberty.
Some research has suggested that kisspeptin has the potential to be used as a diagnostic tool to aid in the early diagnosis and treatment of Kallmann syndrome and related disorders. However, the role of the protein in clinical practice is currently limited, and further research is required.
Some studies have found that continuous administration of kisspeptin eventually leads to a reduced response in the release of GnRH and then LH and FSH. It appears that the efficacy of kisspeptin relies on the presence of sufficient GnRH in the hypothalamus.
The primary clinical and medical research groups for GnRH deficiency disorders such as Kallmann syndrome are:
- Harvard Reproductive Endocrine Sciences, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, USA
- Department of Endocrinology, Diabetes and Metabolism at Centre hospitalier universitaire vaudois, Switzerland.
These are continuing to perform research into the pathophysiology, possible treatment, and prevention techniques, for Kallmann syndrome. As we gain deeper insight into the condition, the treatment options available are expected to become more targeted so as to improve the quality of life for patients with Kallmann syndrome.
To date, mutations in several genes have been associated with causing Kallmann syndrome, including ANOS1, FGFR1, PROKR and PROK 2. ANOS1 appears to follow an X-linked recessive inheritance pattern, which partly explains the predominance of males with the condition, as revealed in epidemiological studies. The other identified gene mutations appear to follow an autosomal recessive inheritance pattern.
However, the identified genes only account for approximately 30% of all cases of Kallmann syndrome. Therefore, there are likely to be many other possible mutations that have the ability to cause the syndrome. Further research is currently going on in this area to identify other causative genes.
Although progress has certainly been made in the scientific research of Kallmann syndrome until now, there remains a significant need for more information to be uncovered. The identification of other causative genes is one such area that needs work. Others include epidemiologic studies to find the actual prevalence of the condition, the phenotypic variations in the condition and further evaluation of the mode of inheritance in families. In addition, more pathological studies to improve the understanding of the mechanism of the condition, and how treatments could change the condition.
Reviewed by Dr Liji Thomas, MD.