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 Kallmann Syndrome -- Questions and Answers 

What is it?
 
Kallmann Syndrome (KS) is comprised of decreased or absent sense of smell and sex steroid hormone deficiency.

What is known about its frequency?
The frequency estimates of KS have been variable and have ranged between 1:4000 to 1:10000 in males and it has been estimated that KS is, for unknown reason, approxiamtely 4-5 times more frequent in males as compared to females. We do not know the frequency of KS in Finland, but this is one topic of our
research.  

 
 What is the cause of KS?
Normally, the onset and progression of puberty is governed by a hormone, GNRH, acting in the central nervous system. Patients with KS lack this hormone which leads to absence of complete puberty. It is currently thought that KS is caused by genetic defects. Quite often, however, the exact molecular genetic cause of KS cannot be found.

What is the link between absent olfaction and puberty? 
It is currently thought that disturbancies in the very early development of the olfactory system also lead to misrouting of GnRH neurons (i.e. these cells do not find their normal place in the central nervous system). This leads to deficient secretion of GnRH.

What are the typical signs of KS?

The typical signs of KS are absent, severly delayed or partial puberty accompanied by decreased or absent sense of smell. It is important to remember, however, that the most common cause of delayed puberty is constitutional delay of growth and puberty (and there is normal sense of smell and no permanent GnRH deficiency) (4). Patients with KS may also display unilateral renal agenesis, synkinesia (mirror movements), midline defects (such as cleft lip and/or palate), or hearing loss (3). The frequency of these defects in KS is highly variable. 
 
 How is KS diagnosed?
   If you suspect KS in yourself or in your child, please contact your  general practitioner, school physician, or private endocrinologist or gynecologist. The diagnosis of KS is always set in tertiary centers (i.e. university hospitals).

What is the treatment for KS? 
      Puberty can be induced with sex hormone therapy. Sometimes the treatment may be initiated at an older age (see the story of 33-yr-old physician of of his life). Infertility can often be treated with hormonal therapies (5), but the defect in olfaction will remain. Quite often KS raises questions and concerns in the proband and his/her family members and counseling of a health care professional and genetic counselling is recommended. 

  

Does KS affect my career planning?
 A bit. Decreased sense of smell may somewhat restrict career plans. In addition, some patients may suffer from mirror movements in hands or upper limbs that may be disadvantageous in certain professions. 

Does KS affect my everyday life?
  Not too much. Inability to sense certain odors  such as gas or smoke can sometimes, however, predispose you to dangerous situations.

 
Is KS always for lifetime?
Not necessarily. Sex hormone deficiency and infertility may sometimes recover at an older age (6), even after many years of sex hormone therapy (7)

Voiko saada lapsia, jos on KS?
Quite often, yes (see also above), although hormone therapy is usually necessary.

How is KS being inherited?
More than half of KS cases are sporadic
(8), meaning that thera are no other patients in the family. In familial cases, different modes of inheritance have been described. 
 

References
1. Pawlowitzki IH, Diekstall P, Schadel A, Miny P. Estimating frequency of Kallmann syndrome among hypogonadic and among anosmic patients. Am J Med Genet 1987;26(2):473-9.

2. Quinton R. Idiopathic Hypogonadotrophic Hypogonadism and Abnormalities of the GnRH Pulse Generator. Topical Endocrinol 22: 15-20.

3. Cariboni A, Maggi R. Kallmann's syndrome, a neuronal migration defect. Cell Mol Life Sci 2006;63(21):2512-26.

4. Sedlmeyer IL, Palmert MR. Delayed puberty: analysis of a large case series from an academic center. J Clin Endocrinol Metab 2002;87(4):1613-20.

5. Pitteloud N, Hayes FJ, Boepple PA, DeCruz S, Seminara SB, MacLaughlin DT, et al. The role of prior pubertal development, biochemical markers of testicular maturation, and genetics in elucidating the phenotypic heterogeneity of idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab 2002;87(1):152-60.

6. Raivio T, Falardeau J, Dwyer A, Quinton R, Hayes FJ, Hughes VA, et al. Reversal of idiopathic hypogonadotropic hypogonadism. N Engl J Med 2007;357(9):863-73.

7. Ribeiro RS, Vieira TC, Abucham J. Reversible Kallmann syndrome: report of the first case with a KAL1 mutation and literature review. Eur J Endocrinol 2007;156(3):285-90.

8. Oliveira LM, Seminara SB, Beranova M, Hayes FJ, Valkenburgh SB, Schipani E, et al. The importance of autosomal genes in Kallmann syndrome: genotype-phenotype correlations and neuroendocrine characteristics. J Clin Endocrinol Metab 2001;86(4):1532-8