Thursday, January 28, 2010

- Kallmann syndrome.

 Kallmann syndrome

- Def :- It is a rare X-linked recessive genetic disease which characterized by delayed or absent puberty and an impaired sense of smell, also referred as olfactogenital dysplasia.

- Kallmann syndrome is a form of secondary hypogonadism, reflecting that the primary cause of the defect in sex-hormone production lies within the pituitary and hypothalamus rather than a physical defect of the testes or ovaries.

- Kallmann syndrome was described in 1944 by Franz Josef Kallmann, a German-American geneticist.(1)(2)

- Incidence:-
It affects primarily males at an incidence of 1 out of 10,000 in a study of French conscripts.(3)
The male-to-female ratio ranges from 4:1 to 5:1.

- Cause:-
Mutations in the KAL1, FGFR1, PROKR2, and PROK2 genes cause Kallmann syndrome.
These genes play a role in the development of certain areas of the brain before birth. Although some of their specific functions are unclear, these genes appear to be involved in the formation and movement (migration) of a group of nerve cells that are specialized to process smells (olfactory neurons).(4)

- Synonyms:-
  • de Morsier’s syndrome II.
  • Morsier-Gauthier syndrome.
  • Kallmann-de Morsier syndrome.
  • Maestre-Kallmann-de Morsier syndrome.
  • Maestre de San Juan-Kallmann syndrome.
  • Maestre de San Juan-Kallmann-de Morsier syndrome.
  • anosmic hypogonadism.
  • anosmic idiopathic hypogonadotropic hypogonadism.
  • hypogonadotropic hypogonadism and anosmia.
  • hypogonadotropic hypogonadism-anosmia syndrome.

- Pathophysiology:-
  • Absence or reduced levels of GnRH production by hypothalamus leading to decrease release of gonadotropins (LH and FSH) from pituitary gland.
  • The GnRH neurons do not migrate properly from the olfactory placode to the hypothalamus during development. The olfactory bulbs also fail to form or have hypoplasia, leading to anosmia or hyposmia.

- Clinical Picture:-
  • Hypogonadism and may be infertile due to affection of the hypothalamus.
  • Congenital anosmia (complete inability to smell) or hyposmia (decreased ability to smell)caused by the absence of the olfactory bulbs.
  • It can occasionally be associated with optic problems, such as colour blindness or optic atrophy.
  • Cleft palate.
  • Hare lip.
  • Osteoporosis:all hypogonadal patients are at high risk of osteoporosis if untreated.
- Diagnosis:-
The diagnosis is often one of exclusion found during the workup of delayed puberty. The presence of anosmia with delayed puberty should suggest Kallmann syndrome.

- Treatment:-
  • Treatment is directed at restoring the deficient hormones—hormone therapy (HT).
  • Males are administered human chorionic gonadotropin (hCG) or testosterone.
  • Females are treated with estrogen and progestins.
  • The main health risk, for both men and women, of untreated Kallmann Syndrome is osteoporosis. Therefore, regular bone-density scans (every two years or so) are advisable and additional medication specifically for osteoporosis is necessary in some cases.
- Psychology:-
In some cases, the psychological effects of having this condition can outweigh the significance of any physical symptoms.

Return to list of medical syndromes here

(1)Kallmann FJ, Schönfeld WA, Barrera SE. The genetic aspects of primary eunuchoidism. Am J Ment Defic 1943-1944;48:203-236.
(3)Fromantin M, Gineste J, Didier A, et al. [Impuberism and hypogonadism at induction into military service. Statistical study]. Probl Actuels Endocrinol Nutr. May 3 1973;16:179-99.
(4) Kallmann syndrome,Genetics Home Reference.

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